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Sample records for virion host shutoff

  1. The herpes simplex virus 1 virion host shutoff protein enhances translation of viral late mRNAs by preventing mRNA overload.

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    Dauber, Bianca; Saffran, Holly A; Smiley, James R

    2014-09-01

    We recently demonstrated that the virion host shutoff (vhs) protein, an mRNA-specific endonuclease, is required for efficient herpes simplex virus 1 (HSV-1) replication and translation of viral true-late mRNAs, but not other viral and cellular mRNAs, in many cell types (B. Dauber, J. Pelletier, and J. R. Smiley, J. Virol. 85:5363-5373, 2011, http://dx.doi.org/10.1128/JVI.00115-11). Here, we evaluated whether the structure of true-late mRNAs or the timing of their transcription is responsible for the poor translation efficiency in the absence of vhs. To test whether the highly structured 5' untranslated region (5'UTR) of the true-late gC mRNA is the primary obstacle for translation initiation, we replaced it with the less structured 5'UTR of the γ-actin mRNA. However, this mutation did not restore translation in the context of a vhs-deficient virus. We then examined whether the timing of transcription affects translation efficiency at late times. To this end, we engineered a vhs-deficient virus mutant that transcribes the true-late gene US11 with immediate-early kinetics (IEUS11-ΔSma). Interestingly, IEUS11-ΔSma showed increased translational activity on the US11 transcript at late times postinfection, and US11 protein levels were restored to wild-type levels. These results suggest that mRNAs can maintain translational activity throughout the late stage of infection if they are present before translation factors and/or ribosomes become limiting. Taken together, these results provide evidence that in the absence of the mRNA-destabilizing function of vhs, accumulation of viral mRNAs overwhelms the capacity of the host translational machinery, leading to functional exclusion of the last mRNAs that are made during infection. The process of mRNA translation accounts for a significant portion of a cell's energy consumption. To ensure efficient use of cellular resources, transcription, translation, and mRNA decay are tightly linked and highly regulated. However, during

  2. Proinflammatory cytokines and chemokines - but not interferon-β - produced in response to HSV-2 in primary human genital epithelial cells are associated with viral replication and the presence of the virion host shutoff protein.

    Science.gov (United States)

    Ferreira, Victor H; Nazli, Aisha; Mossman, Karen L; Kaushic, Charu

    2013-09-01

    It is unknown whether viral replication or viral components that subvert innate responses in other cells, specifically the virion host shutoff (VHS) protein, play a role in determining primary genital epithelial cell (GEC) innate antiviral responses. Cultures of primary female GECs were exposed to wildtype (WT), VHS-deleted (vhsB), or UV-inactivated HSV-2. Antiviral pathway induction was evaluated by measuring nuclear factor-κB (NFκB) translocation by immunofluorescent microscopy. Proinflammatory cytokines, chemokines, and interferon (IFN) were measured by Luminex or ELISA. Biological activity of IFN-β was evaluated via VSV-GFP bioassay, by blocking secreted IFN-β with neutralizing antibodies and by measuring interferon-stimulated genes by RT-PCR. Proinflammatory cytokines and chemokines were upregulated in primary GECs in response to replication-competent HSV-2, but suppressed in the presence of the VHS protein. In contrast, upregulation of IFN-β depended on viral replication, but was not affected by VHS. However, the IFN-β produced was biologically active and reduced the viral burden. Viral factors such as replication and the presence of the VHS protein play important roles in regulating innate antiviral responses against HSV-2 from primary GECs. © 2013 John Wiley & Sons Ltd.

  3. Infectious bronchitis coronavirus limits interferon production by inducing a host shutoff that requires accessory protein 5b

    NARCIS (Netherlands)

    Kint, Joeri; Langereis, Martijn A.; Maier, Helena J.; Britton, Paul; Kuppeveld, van Frank J.; Koumans, Joseph; Wiegertjes, Geert F.; Forlenza, Maria

    2016-01-01

    During infection of their host cells, viruses often inhibit the production of host proteins, a process that is referred to as host shutoff. By doing this, viruses limit the production of antiviral proteins and increase production capacity for viral proteins. Coronaviruses from the genera

  4. Infectious bronchitis coronavirus limits interferon production by inducing a host shutoff that requires accessory protein 5b

    NARCIS (Netherlands)

    Kint, Joeri; Langereis, Martijn A|info:eu-repo/dai/nl/304823597; Maier, Helena J; Britton, Paul; van Kuppeveld, Frank J|info:eu-repo/dai/nl/156614723; Koumans, Joseph; Wiegertjes, Geert F; Forlenza, Maria

    2016-01-01

    During infection of their host cell, viruses often inhibit production of host proteins, a process which is referred to as host shutoff. By doing this, viruses limit production of antiviral proteins and increase production capacity for viral proteins. Coronaviruses from the Alpha- and Betacoronavirus

  5. KSHV SOX mediated host shutoff: the molecular mechanism underlying mRNA transcript processing.

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    Lee, Hyunah; Patschull, Anathe O M; Bagnéris, Claire; Ryan, Hannah; Sanderson, Christopher M; Ebrahimi, Bahram; Nobeli, Irene; Barrett, Tracey E

    2017-05-05

    Onset of the lytic phase in the KSHV life cycle is accompanied by the rapid, global degradation of host (and viral) mRNA transcripts in a process termed host shutoff. Key to this destruction is the virally encoded alkaline exonuclease SOX. While SOX has been shown to possess an intrinsic RNase activity and a potential consensus sequence for endonucleolytic cleavage identified, the structures of the RNA substrates targeted remained unclear. Based on an analysis of three reported target transcripts, we were able to identify common structures and confirm that these are indeed degraded by SOX in vitro as well as predict the presence of such elements in the KSHV pre-microRNA transcript K12-2. From these studies, we were able to determine the crystal structure of SOX productively bound to a 31 nucleotide K12-2 fragment. This complex not only reveals the structural determinants required for RNA recognition and degradation but, together with biochemical and biophysical studies, reveals distinct roles for residues implicated in host shutoff. Our results further confirm that SOX and the host exoribonuclease Xrn1 act in concert to elicit the rapid degradation of mRNA substrates observed in vivo, and that the activities of the two ribonucleases are co-ordinated. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Analysis of virion associated host proteins in vesicular stomatitis virus using a proteomics approach

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    Hwang Sun-Il

    2009-10-01

    Full Text Available Abstract Background Vesicular stomatitis virus (VSV is the prototypic rhabdovirus and the best studied member of the order Mononegavirales. There is now compelling evidence that enveloped virions released from infected cells carry numerous host (cellular proteins some of which may play an important role in viral replication. Although several cellular proteins have been previously shown to be incorporated into VSV virions, no systematic study has been done to reveal the host protein composition for virions of VSV or any other member of Mononegavirales. Results Here we used a proteomics approach to identify cellular proteins within purified VSV virions, thereby creating a "snapshot" of one stage of virus/host interaction that can guide future experiments aimed at understanding molecular mechanisms of virus-cell interactions. Highly purified preparations of VSV virions from three different cell lines of human, mouse and hamster origin were analyzed for the presence of cellular proteins using mass spectrometry. We have successfully confirmed the presence of several previously-identified cellular proteins within VSV virions and identified a number of additional proteins likely to also be present within the virions. In total, sixty-four cellular proteins were identified, of which nine were found in multiple preparations. A combination of immunoblotting and proteinase K protection assay was used to verify the presence of several of these proteins (integrin β1, heat shock protein 90 kDa, heat shock cognate 71 kDa protein, annexin 2, elongation factor 1a within the virions. Conclusion This is, to our knowledge, the first systematic study of the host protein composition for virions of VSV or any other member of the order Mononegavirales. Future experiments are needed to determine which of the identified proteins have an interaction with VSV and whether these interactions are beneficial, neutral or antiviral with respect to VSV replication. Identification

  7. Purification of infectious human herpesvirus 6A virions and association of host cell proteins

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    Garoff Henrik

    2007-10-01

    Full Text Available Abstract Background Viruses that are incorporating host cell proteins might trigger autoimmune diseases. It is therefore of interest to identify possible host proteins associated with viruses, especially for enveloped viruses that have been suggested to play a role in autoimmune diseases, like human herpesvirus 6A (HHV-6A in multiple sclerosis (MS. Results We have established a method for rapid and morphology preserving purification of HHV-6A virions, which in combination with parallel analyses with background control material released from mock-infected cells facilitates qualitative and quantitative investigations of the protein content of HHV-6A virions. In our iodixanol gradient purified preparation, we detected high levels of viral DNA by real-time PCR and viral proteins by metabolic labelling, silver staining and western blots. In contrast, the background level of cellular contamination was low in the purified samples as demonstrated by the silver staining and metabolic labelling analyses. Western blot analyses showed that the cellular complement protein CD46, the receptor for HHV-6A, is associated with the purified and infectious virions. Also, the cellular proteins clathrin, ezrin and Tsg101 are associated with intact HHV-6A virions. Conclusion Cellular proteins are associated with HHV-6A virions. The relevance of the association in disease and especially in autoimmunity will be further investigated.

  8. Proteomic Analysis of Mamestra Brassicae Nucleopolyhedrovirus Progeny Virions from Two Different Hosts.

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    Dianhai Hou

    Full Text Available Mamestra brassicae nucleopolyhedrovirus (MabrNPV has a wide host range replication in more than one insect species. In this study, a sequenced MabrNPV strain, MabrNPV-CTa, was used to perform proteomic analysis of both BVs and ODVs derived from two infected hosts: Helicoverpa armigera and Spodoptera exigua. A total of 82 and 39 viral proteins were identified in ODVs and BVs, respectively. And totally, 23 and 76 host proteins were identified as virion-associated with ODVs and BVs, respectively. The host proteins incorporated into the virus particles were mainly involved in cytoskeleton, signaling, vesicle trafficking, chaperone and metabolic systems. Some host proteins, such as actin, cyclophilin A and heat shock protein 70 would be important for viral replication. Several host proteins involved in immune response were also identified in BV, and a C-type lectin protein was firstly found to be associated with BV and its family members have been demonstrated to be involved in entry process of other viruses. This study facilitated the annotation of baculovirus genome, and would help us to understand baculovirus virion structure. Furthermore, the identification of host proteins associated with virions produced in vivo would facilitate investigations on the involvement of intriguing host proteins in virus replication.

  9. The plant host can affect the encapsidation of brome mosaic virus (BMV) RNA: BMV virions are surprisingly heterogeneous.

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    Ni, Peng; Vaughan, Robert C; Tragesser, Brady; Hoover, Haley; Kao, C Cheng

    2014-03-06

    Brome mosaic virus (BMV) packages its genomic and subgenomic RNAs into three separate viral particles. BMV purified from barley, wheat, and tobacco have distinct relative abundances of the encapsidated RNAs. We seek to identify the basis for the host-dependent differences in viral RNA encapsidation. Sequencing of the viral RNAs revealed recombination events in the 3' untranslated region of RNA1 of BMV purified from barley and wheat, but not from tobacco. However, the relative amounts of the BMV RNAs that accumulated in barley and wheat are similar and RNA accumulation is not sufficient to account for the difference in RNA encapsidation. Virions purified from barley and wheat were found to differ in their isoelectric points, resistance to proteolysis, and contacts between the capsid residues and the RNA. Mass spectrometric analyses revealed that virions from the three hosts had different post-translational modifications that should impact the physiochemical properties of the virions. Another major source of variation in RNA encapsidation was due to the purification of BMV particles to homogeneity. Highly enriched BMV present in lysates had a surprising range of sizes, buoyant densities, and distinct relative amounts of encapsidated RNAs. These results show that the encapsidated BMV RNAs reflect a combination of host effects on the physiochemical properties of the viral capsids and the enrichment of a subset of virions. The previously unexpected heterogeneity in BMV should influence the timing of the infection and also the host innate immune responses. © 2013.

  10. Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

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    Geyer Matthias

    2007-10-01

    Full Text Available Abstract Background The Nef protein of Human Immunodeficiency Viruses optimizes viral spread in the infected host by manipulating cellular transport and signal transduction machineries. Nef also boosts the infectivity of HIV particles by an unknown mechanism. Recent studies suggested a correlation between the association of Nef with lipid raft microdomains and its positive effects on virion infectivity. Furthermore, the lipidome analysis of HIV-1 particles revealed a marked enrichment of classical raft lipids and thus identified HIV-1 virions as an example for naturally occurring membrane microdomains. Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition. Results Quantitative mass spectrometric lipidome analysis of highly purified HIV-1 particles revealed that the presence of Nef during virus production from T lymphocytes enforced their raft character via a significant reduction of polyunsaturated phosphatidylcholine species and a specific enrichment of sphingomyelin. In contrast, Nef did not significantly affect virion levels of phosphoglycerolipids or cholesterol. The observed alterations in virion lipid composition were insufficient to mediate Nef's effect on particle infectivity and Nef augmented virion infectivity independently of whether virus entry was targeted to or excluded from membrane microdomains. However, altered lipid compositions similar to those observed in virions were also detected in detergent-resistant membrane preparations of virus producing cells. Conclusion Nef alters not only the proteome but also the lipid composition of host cell microdomains. This novel activity represents a previously unrecognized mechanism by which Nef could manipulate HIV-1 target cells to facilitate virus propagation in vivo.

  11. Alteration of vesicular stomatitis virus L and NS proteins by uv irradiation: implications for the mechanism of host cell shut-off

    Energy Technology Data Exchange (ETDEWEB)

    Whitaker-Dowling, P.; Youngner, J.S.

    1988-05-01

    When purified, (/sup 35/S)methionine-labeled vesicular stomatitis virus (VSV) was exposed to ultraviolet light, an irradiation-induced change in the viral proteins was detected by SDS-polyacrylamide gel electrophoresis and immunoblotting. With dose of uv irradiation in the same range as that required to inactivate VSV leader RNA, a loss occurred in the bands corresponding to the L and NS proteins concomitant with the appearance of several new bands of radioactivity throughout the gel. This alteration of viral proteins correlated with the loss of ability of the virus to inhibit host macromolecular synthesis. In light of these results, the role that has been ascribed to the VSV leader RNA in VSV-mediated host shut-off needs to be reevaluated.

  12. Analysis of virion-incorporated host proteins required for herpes simplex virus type 1 infection through a RNA interference screen.

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    Camille Stegen

    Full Text Available Viruses are strictly dependent on cells to propagate and many incorporate host proteins in their viral particles, but the significance of this incorporation is poorly understood. Recently, we performed the first comprehensive characterization of the mature herpes simplex virus type 1 (HSV-1 in which up to 49 distinct cellular proteins were identified by mass spectrometry. In the present study, we sought to identify if these cellular factors are relevant for the HSV-1 life cycle. To this end, we performed a small interfering RNA functional screen and found that 15 of these host proteins altered HSV-1 proliferation in cell culture, without any significant effect on cell viability. Moreover, the siRNA used had no negative consequences for Adenovirus type 5 propagation (with one exception indicating that the modulation was specific for HSV-1 and not merely due to unhealthy cells. The positive host proteins include several Rab GTPases and other intracellular transport components as well as proteins involved in signal transduction, gene regulation and immunity. Remarkably, in most cases when virions were depleted for one of the above proteins, they replicated more poorly in subsequent infections in wild type cells. This highlights for the first time that both the cellular and virion-associated pools of many of these proteins actively contribute to viral propagation. Altogether, these findings underscore the power and biological relevance of combining proteomics and RNA interference to identify novel host-pathogen interactions.

  13. Virions at the gates: receptors and the host-virus arms race.

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    John M Coffin

    Full Text Available All viruses need to bind to specific receptor molecules on the surface of target cells to initiate infection. Virus-receptor binding is highly specific, and this specificity determines both the species and the cell type that can be infected by a given virus. In some well-studied cases, the virus-binding region on the receptor has been found to be unrelated to the receptor's normal cellular function. Resistance to virus infection can thus evolve by selection of mutations that alter amino acids in the binding region with minimal effect on normal function. This sort of positive selection can be used to infer the history of the host-virus "arms race" during their coevolution. In a new study, Demogines et al. use a combination of phylogenetic, structural, and virological analysis to infer the history and significance of positive selection on the transferrin receptor TfR1, a housekeeping protein required for iron uptake and the cell surface receptor for at least three different types of virus. The authors show that only two parts of the rodent TfR1 molecule have been subject to positive selection and that these correspond to the binding sites for two of these viruses-the mouse mammary tumor virus (a retrovirus and Machupo virus (an arenavirus. They confirmed this result by introducing the inferred binding site mutations into the wild-type protein and testing for receptor function. Related arenaviruses are beginning to spread in human populations in South America as the cause of often fatal hemorrhagic fevers, and, although Demogines et al. could find no evidence of TfR1 mutations in this region that might have been selected as a consequence of human infection, the authors identified one such mutation in Asian populations that affects infection with these viruses.

  14. SAFETY SHUTOFF VALVE

    DEFF Research Database (Denmark)

    2010-01-01

    resulted from collision or effusion. A static tower has been applied for the main core of this part of the valve which loses balance state under the effect of collision and bounces to the neighboring part, which results in release of the catch and blockage of the gas passing channel.......It is disclosed a shut-off valve which acts automatically and has a fully mechanical performance with respect to the loosing of the tower-shape part balance under the effect of the special acceleration Which is arisen from the quakes waves or serious vibrations, while such vibrations are mainly...

  15. Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

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    Jonathan E Nuss

    Full Text Available Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV. Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90, as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.

  16. Proteomic characterization of murid herpesvirus 4 extracellular virions.

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    Sarah Vidick

    Full Text Available Gammaherpesvirinae, such as the human Epstein-Barr virus (EBV and the Kaposi's sarcoma associated herpesvirus (KSHV are highly prevalent pathogens that have been associated with several neoplastic diseases. As EBV and KSHV are host-range specific and replicate poorly in vitro, animal counterparts such as Murid herpesvirus-4 (MuHV-4 have been widely used as models. In this study, we used MuHV-4 in order to improve the knowledge about proteins that compose gammaherpesviruses virions. To this end, MuHV-4 extracellular virions were isolated and structural proteins were identified using liquid chromatography tandem mass spectrometry-based proteomic approaches. These analyses allowed the identification of 31 structural proteins encoded by the MuHV-4 genome which were classified as capsid (8, envelope (9, tegument (13 and unclassified (1 structural proteins. In addition, we estimated the relative abundance of the identified proteins in MuHV-4 virions by using exponentially modified protein abundance index analyses. In parallel, several host proteins were found in purified MuHV-4 virions including Annexin A2. Although Annexin A2 has previously been detected in different virions from various families, its role in the virion remains controversial. Interestingly, despite its relatively high abundance in virions, Annexin A2 was not essential for the growth of MuHV-4 in vitro. Altogether, these results extend previous work aimed at determining the composition of gammaherpesvirus virions and provide novel insights for understanding MuHV-4 biology.

  17. Cellular proteins associated with the interior and exterior of vesicular stomatitis virus virions.

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    Moerdyk-Schauwecker, Megan; Hwang, Sun-Il; Grdzelishvili, Valery Z

    2014-01-01

    Virus particles (virions) often contain not only virus-encoded but also host-encoded proteins. Some of these host proteins are enclosed within the virion structure, while others, in the case of enveloped viruses, are embedded in the host-derived membrane. While many of these host protein incorporations are likely accidental, some may play a role in virus infectivity, replication and/or immunoreactivity in the next host. Host protein incorporations may be especially important in therapeutic applications where large numbers of virus particles are administered. Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and a candidate vaccine, gene therapy and oncolytic vector. Using mass spectrometry, we previously examined cell type dependent host protein content of VSV virions using intact ("whole") virions purified from three cell lines originating from different species. Here we aimed to determine the localization of host proteins within the VSV virions by analyzing: i) whole VSV virions; and ii) whole VSV virions treated with Proteinase K to remove all proteins outside the viral envelope. A total of 257 proteins were identified, with 181 identified in whole virions and 183 identified in Proteinase K treated virions. Most of these proteins have not been previously shown to be associated with VSV. Functional enrichment analysis indicated the most overrepresented categories were proteins associated with vesicles, vesicle-mediated transport and protein localization. Using western blotting, the presence of several host proteins, including some not previously shown in association with VSV (such as Yes1, Prl1 and Ddx3y), was confirmed and their relative quantities in various virion fractions determined. Our study provides a valuable inventory of virion-associated host proteins for further investigation of their roles in the replication cycle, pathogenesis and immunoreactivity of VSV.

  18. Cellular proteins associated with the interior and exterior of vesicular stomatitis virus virions.

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    Megan Moerdyk-Schauwecker

    Full Text Available Virus particles (virions often contain not only virus-encoded but also host-encoded proteins. Some of these host proteins are enclosed within the virion structure, while others, in the case of enveloped viruses, are embedded in the host-derived membrane. While many of these host protein incorporations are likely accidental, some may play a role in virus infectivity, replication and/or immunoreactivity in the next host. Host protein incorporations may be especially important in therapeutic applications where large numbers of virus particles are administered. Vesicular stomatitis virus (VSV is the prototypic rhabdovirus and a candidate vaccine, gene therapy and oncolytic vector. Using mass spectrometry, we previously examined cell type dependent host protein content of VSV virions using intact ("whole" virions purified from three cell lines originating from different species. Here we aimed to determine the localization of host proteins within the VSV virions by analyzing: i whole VSV virions; and ii whole VSV virions treated with Proteinase K to remove all proteins outside the viral envelope. A total of 257 proteins were identified, with 181 identified in whole virions and 183 identified in Proteinase K treated virions. Most of these proteins have not been previously shown to be associated with VSV. Functional enrichment analysis indicated the most overrepresented categories were proteins associated with vesicles, vesicle-mediated transport and protein localization. Using western blotting, the presence of several host proteins, including some not previously shown in association with VSV (such as Yes1, Prl1 and Ddx3y, was confirmed and their relative quantities in various virion fractions determined. Our study provides a valuable inventory of virion-associated host proteins for further investigation of their roles in the replication cycle, pathogenesis and immunoreactivity of VSV.

  19. Chemical water shutoff profile research status and development trends

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    Xu, L. T.

    2017-08-01

    Excess water production is now a common problem encountered in almost every water flooding mature oilfield. The exploitation of oil field is faced with great challenge because of the decrease of oil field production. For the development of high water cut rare the status quo chemical water shutoff profile control technology is an important solution to solve this problem. Oilfield chemical water shutoff has important application prospects. This paper analyzes the water shutoff profile control and water shutoff profile control agent currently oilfield applications, moreover the use and development of blocking agent profile technology is to improve reservoir recovery and propose solutions. With the constant increase in water cut, profile technology should be simple, efficient, practical and profile control agent of development should be economic, environmental, and long period

  20. Protein Primary Structure of the Vaccinia Virion at Increased Resolution

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    Ngo, Tuan; Mirzakhanyan, Yeva; Moussatche, Nissin; Gershon, Paul David

    2016-11-01

    Here we examine the protein covalent structure of the vaccinia virus virion. Within two virion preparations, >88% of the theoretical vaccinia virus-encoded proteome was detected with high confidence, including the first detection of products from 27 open reading frames (ORFs) previously designated "predicted," "uncharacterized," "inferred," or "hypothetical" polypeptides containing as few as 39 amino acids (aa) and six proteins whose detection required nontryptic proteolysis. We also detected the expression of four short ORFs, each of which was located within an ORF ("ORF-within-ORF"), including one not previously recognized or known to be expressed. Using quantitative mass spectrometry (MS), between 58 and 74 proteins were determined to be packaged. A total of 63 host proteins were also identified as candidates for packaging. Evidence is provided that some portion of virion proteins are "nicked" via a combination of endoproteolysis and concerted exoproteolysis in a manner, and at sites, independent of virus origin or laboratory procedures. The size of the characterized virion phosphoproteome was doubled from 189 (J. Matson, W. Chou, T. Ngo, and P. D. Gershon, Virology 452-453:310-323, 2014, doi:http://dx.doi.org/10.1016/j.virol.2014.01.012) to 396 confident, unique phosphorylation sites, 268 of which were within the packaged proteome. This included the unambiguous identification of phosphorylation "hot spots" within virion proteins. Using isotopically enriched ATP, 23 sites of intravirion kinase phosphorylation were detected within nine virion proteins, all at sites already partially occupied within the virion preparations. The clear phosphorylation of proteins RAP94 and RP19 was consistent with the roles of these proteins in intravirion early gene transcription. In a blind search for protein modifications, cysteine glutathionylation and O-linked glycosylation featured prominently. We provide evidence for the phosphoglycosylation of vaccinia virus proteins

  1. Proteomic analysis of the EhV-86 virion.

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    Allen, Michael J; Howard, Julie A; Lilley, Kathryn S; Wilson, William H

    2008-03-17

    Emiliania huxleyi virus 86 (EhV-86) is the type species of the genus Coccolithovirus within the family Phycodnaviridae. The fully sequenced 407,339 bp genome is predicted to encode 473 protein coding sequences (CDSs) and is the largest Phycodnaviridae sequenced to date. The majority of EhV-86 CDSs exhibit no similarity to proteins in the public databases. Proteomic analysis by 1-DE and then LC-MS/MS determined that the virion of EhV-86 is composed of at least 28 proteins, 23 of which are predicted to be membrane proteins. Besides the major capsid protein, putative function can be assigned to 4 other components of the virion: two lectin proteins, a thioredoxin and a serine/threonine protein kinase. This study represents the first steps toward the identification of the protein components that make up the EhV-86 virion. Aside from the major capsid protein, whose function in the virion is well known and defined, the nature of the other proteins suggest roles involved with viral budding, caspase activation, signalling, anti-oxidation, virus adsorption and host range determination.

  2. Proteomic analysis of the EhV-86 virion

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    Lilley Kathryn S

    2008-03-01

    Full Text Available Abstract Background Emiliania huxleyi virus 86 (EhV-86 is the type species of the genus Coccolithovirus within the family Phycodnaviridae. The fully sequenced 407,339 bp genome is predicted to encode 473 protein coding sequences (CDSs and is the largest Phycodnaviridae sequenced to date. The majority of EhV-86 CDSs exhibit no similarity to proteins in the public databases. Results Proteomic analysis by 1-DE and then LC-MS/MS determined that the virion of EhV-86 is composed of at least 28 proteins, 23 of which are predicted to be membrane proteins. Besides the major capsid protein, putative function can be assigned to 4 other components of the virion: two lectin proteins, a thioredoxin and a serine/threonine protein kinase. Conclusion This study represents the first steps toward the identification of the protein components that make up the EhV-86 virion. Aside from the major capsid protein, whose function in the virion is well known and defined, the nature of the other proteins suggest roles involved with viral budding, caspase activation, signalling, anti-oxidation, virus adsorption and host range determination.

  3. Performance of the NRX shut-off rods

    Energy Technology Data Exchange (ETDEWEB)

    Manson, R.E.

    1965-08-15

    A new type of shut-off rod of electromechanical design was developed by the American Machine and Foundry Company for use in the NRX reactor following the accident of 1952. The new rods were installed in May, 1956, as part of the control system conversion program which was completed in 1958. Some problems were encountered with limit switch adjustment but minor modifications in design led to much improved operation. he performance of the rods also improved as more experience was gained in the maintenance and adjustment of the various headgear components. Each headgear is now overhauled once a year on a routine basis. The present design of shut-off rod is considered to be very satisfactory. There has only been one occasion when a shut-off rod has failed to come fully down on a trip. Rods have failed to operate correctly on five other occasions but these occurred during shutdown periods or when the reactor was being shutdown manually. (author)

  4. Identification of bacteriophage virion proteins by the ANOVA feature selection and analysis.

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    Ding, Hui; Feng, Peng-Mian; Chen, Wei; Lin, Hao

    2014-08-01

    The bacteriophage virion proteins play extremely important roles in the fate of host bacterial cells. Accurate identification of bacteriophage virion proteins is very important for understanding their functions and clarifying the lysis mechanism of bacterial cells. In this study, a new sequence-based method was developed to identify phage virion proteins. In the new method, the protein sequences were initially formulated by the g-gap dipeptide compositions. Subsequently, the analysis of variance (ANOVA) with incremental feature selection (IFS) was used to search for the optimal feature set. It was observed that, in jackknife cross-validation, the optimal feature set including 160 optimized features can produce the maximum accuracy of 85.02%. By performing feature analysis, we found that the correlation between two amino acids with one gap was more important than other correlations for phage virion protein prediction and that some of the 1-gap dipeptides were important and mainly contributed to the virion protein prediction. This analysis will provide novel insights into the function of phage virion proteins. On the basis of the proposed method, an online web-server, PVPred, was established and can be freely accessed from the website (http://lin.uestc.edu.cn/server/PVPred). We believe that the PVPred will become a powerful tool to study phage virion proteins and to guide the related experimental validations.

  5. Role of Human Cytomegalovirus Tegument Proteins in Virion Assembly

    Science.gov (United States)

    Smith, Rebecca Marie; Kosuri, Srivenkat; Kerry, Julie Anne

    2014-01-01

    Like other herpesviruses, human cytomegalovirus (HCMV) contains a unique proteinaceous layer between the virion envelope and capsid, termed the tegument. Upon infection, the contents of the tegument layer are delivered to the host cell, along with the capsid and the viral genome, where they facilitate the initial stages of virus replication. The tegument proteins also play important roles in virion assembly and this dual nature makes them attractive potential targets for antiviral therapies. While our knowledge regarding tegument protein function during the initiation of infection has been the subject of intense study, their roles in assembly are much less well understood. In this review, we will focus on recent studies that highlight the functions of HCMV tegument proteins during assembly, and pose key questions for further investigation. PMID:24509811

  6. Endophilins interact with Moloney murine leukemia virus Gag and modulate virion production

    Directory of Open Access Journals (Sweden)

    De Camilli Pietro

    2003-12-01

    Full Text Available Abstract Background The retroviral Gag protein is the central player in the process of virion assembly at the plasma membrane, and is sufficient to induce the formation and release of virus-like particles. Recent evidence suggests that Gag may co-opt the host cell's endocytic machinery to facilitate retroviral assembly and release. Results A search for novel partners interacting with the Gag protein of the Moloney murine leukemia virus (Mo-MuLV via the yeast two-hybrid protein-protein interaction assay resulted in the identification of endophilin 2, a component of the machinery involved in clathrin-mediated endocytosis. We demonstrate that endophilin interacts with the matrix or MA domain of the Gag protein of Mo-MuLV, but not of human immunodeficiency virus, HIV. Both exogenously expressed and endogenous endophilin are incorporated into Mo-MuLV viral particles. Titration experiments suggest that the binding sites for inclusion of endophilin into viral particles are limited and saturable. Knock-down of endophilin with small interfering RNA (siRNA had no effect on virion production, but overexpression of endophilin and, to a lesser extent, of several fragments of the protein, result in inhibition of Mo-MuLV virion production, but not of HIV virion production. Conclusions This study shows that endophilins interact with Mo-MuLV Gag and affect virion production. The findings imply that endophilin is another component of the large complex that is hijacked by retroviruses to promote virion production.

  7. Protein Composition of the Bovine Herpesvirus 1.1 Virion

    Science.gov (United States)

    Barber, Kaley A.; Daugherty, Hillary C.; Ander, Stephanie E.; Jefferson, Victoria A.; Shack, Leslie A.; Pechan, Tibor; Nanduri, Bindu; Meyer, Florencia

    2017-01-01

    Bovine herpesvirus (BoHV) type 1 is an important agricultural pathogen that infects cattle and other ruminants worldwide. Acute infection of the oro-respiratory tract leads to immune suppression and allows commensal bacteria to infect an otherwise healthy lower respiratory tract. This condition is known as the Bovine Respiratory Disease (BRD). BoHV-1 latently infects the host for life and periodical stress events re-initiate BRD, translating into high morbidity and large economic losses. To gain a better understanding of the biology of BoHV-1 and the disease it causes, we elucidated the protein composition of extracellular virions using liquid chromatography-mass spectrometry analysis. We detected 33 viral proteins, including the expected proteins of the nucleocapsid and envelope as well as other regulatory proteins present in the viral tegument. In addition to viral proteins, we have also identified packaged proteins of host origin. This constitutes the first proteomic characterization of the BoHV virion. PMID:29056670

  8. RAB1A promotes Vaccinia virus replication by facilitating the production of intracellular enveloped virions

    Energy Technology Data Exchange (ETDEWEB)

    Pechenick Jowers, Tali; Featherstone, Rebecca J.; Reynolds, Danielle K.; Brown, Helen K. [The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9RG, Scotland (United Kingdom); James, John; Prescott, Alan [Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom); Haga, Ismar R. [The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9RG, Scotland (United Kingdom); Beard, Philippa M., E-mail: pip.beard@roslin.ed.ac.uk [The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9RG, Scotland (United Kingdom)

    2015-01-15

    Vaccinia virus (VACV) is a large double-stranded DNA virus with a complex cytoplasmic replication cycle that exploits numerous cellular proteins. This work characterises the role of a proviral cellular protein, the small GTPase RAB1A, in VACV replication. Using siRNA, we identified RAB1A as required for the production of extracellular enveloped virions (EEVs), but not intracellular mature virions (IMVs). Immunofluorescence and electron microscopy further refined the role of RAB1A as facilitating the wrapping of IMVs to become intracellular enveloped virions (IEVs). This is consistent with the known function of RAB1A in maintenance of ER to Golgi transport. VACV can therefore be added to the growing list of viruses which require RAB1A for optimal replication, highlighting this protein as a broadly proviral host factor. - Highlights: • Characterisation of the role of the small GTPase RAB1A in VACV replication. • RAB1A is not required for production of the primary virion form (IMV). • RAB1A is required for production of processed virion forms (IEVs, CEVs and EEVs). • Consistent with known role of RAB1A in ER to Golgi transport.

  9. Fluid dynamics following flow shut-off in bottle filling

    Science.gov (United States)

    Thete, Sumeet; Appathurai, Santosh; Gao, Haijing; Basaran, Osman

    2012-11-01

    Bottle filling is ubiquitous in industry. Examples include filling of bottles with shampoos and cleaners, engine oil and pharmaceuticals. In these examples, fluid flows out of a nozzle to fill bottles in an assembly line. Once the required volume of fluid has flowed out of the nozzle, the flow is shut off. However, an evolving fluid thread or string may remain suspended from the nozzle following flow shut-off and persist. This stringing phenomenon can be detrimental to a bottle filling operation because it can adversely affect line speed and filling accuracy by causing uncertainty in fill volume, product loss and undesirable marring of the bottles' exterior surfaces. The dynamics of stringing are studied numerically primarily by using the 1D, slender-jet approximation of the flow equations. A novel feature entails development and use of a new boundary condition downstream of the nozzle exit to expedite the computations. While the emphasis is on stringing of Newtonian fluids and use of 1D approximations, results will also be presented for situations where (a) the fluids are non-Newtonian and (b) the full set of equations are solved without invoking the 1D approximation. Phase diagrams will be presented that identify conditions for which stringing can be problematic.

  10. Interactions between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly.

    Science.gov (United States)

    Dilley, Kari A; Nikolaitchik, Olga A; Galli, Andrea; Burdick, Ryan C; Levine, Louis; Li, Kelvin; Rein, Alan; Pathak, Vinay K; Hu, Wei-Shau

    2017-08-15

    Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious viruslike particles, and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus. However, such enhancement is diminished when Gag is overexpressed, suggesting that the effects of viral RNA can be replaced by increased Gag concentration in cells. We also showed that the specific interactions between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA-Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged into each nascent virion. These studies shed light on the mechanism by which HIV-1 achieves efficient genome packaging during virus assembly.IMPORTANCE Retrovirus assembly is a well-choreographed event, during which many viral and cellular components come together to generate infectious virions. The viral RNA genome carries the genetic information to new host cells, providing instructions to generate new virions, and therefore is essential for virion infectivity. In this report, we show that the specific interaction of the viral RNA genome with the structural protein Gag facilitates virion assembly and particle production. These findings resolve the conundrum that HIV-1 RNA is selectively packaged into virions with high efficiency despite being dispensable for virion assembly

  11. Development of a promoter shutoff system in Aspergillus oryzae using a sorbitol-sensitive promoter.

    Science.gov (United States)

    Oda, Ken; Terado, Shiho; Toyoura, Rieko; Fukuda, Hisashi; Kawauchi, Moriyuki; Iwashita, Kazuhiro

    2016-09-01

    Promoter shutoff is a general method for analyzing essential genes, but in the fungus Aspergillus oryzae, no tightly repressed promoters have been reported. To overcome the current limitations of conditional promoters, we examined sorbitol- and galactose-responsive genes using microarrays to identify regulatable genes with only minor physiological and genetic effects. We identified two sorbitol-induced genes (designated as sorA and sorB), cloned their promoters, and built a regulated egfp and brlA expression system. Growth medium-dependent enhanced green fluorescence protein (EGFP) fluorescence and conidiation were confirmed for egfp and brlA under the control of their respective promoters. We also used this shutoff system to regulate the essential rhoA, which demonstrated the expected growth inhibition under repressed growth conditions. Our new sorbitol promoter shutoff system developed can serve as a valuable new tool for essential gene analyses of filamentous fungi.

  12. Exocytosis of Alphaherpesvirus Virions, Light Particles, and Glycoproteins Uses Constitutive Secretory Mechanisms.

    Science.gov (United States)

    Hogue, Ian B; Scherer, Julian; Enquist, Lynn W

    2016-06-07

    Many molecular and cell biological details of the alphaherpesvirus assembly and egress pathway remain unclear. Recently we developed a live-cell fluorescence microscopy assay of pseudorabies virus (PRV) exocytosis, based on total internal reflection fluorescence (TIRF) microscopy and a virus-encoded pH-sensitive fluorescent probe. Here, we use this assay to distinguish three classes of viral exocytosis in a nonpolarized cell type: (i) trafficking of viral glycoproteins to the plasma membrane, (ii) exocytosis of viral light particles, and (iii) exocytosis of virions. We find that viral glycoproteins traffic to the cell surface in association with constitutive secretory Rab GTPases and exhibit free diffusion into the plasma membrane after exocytosis. Similarly, both virions and light particles use these same constitutive secretory mechanisms for egress from infected cells. Furthermore, we show that viral light particles are distinct from cellular exosomes. Together, these observations shed light on viral glycoprotein trafficking steps that precede virus particle assembly and reinforce the idea that virions and light particles share a biogenesis and trafficking pathway. The alphaherpesviruses, including the important human pathogens herpes simplex virus 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), are among the few viruses that have evolved to exploit the mammalian nervous system. These viruses typically cause mild recurrent herpetic or zosteriform lesions but can also cause debilitating herpes encephalitis, more frequently in very young, old, immunocompromised, or nonnatural hosts. Importantly, many of the molecular and cellular mechanisms of viral assembly and egress remain unclear. This study addresses the trafficking of viral glycoproteins to the plasma membrane, exocytosis of light particles, and exocytosis of virions. Trafficking of glycoproteins affects immune evasion and pathogenesis and may precede virus particle assembly. The release of light

  13. Structural lability of Barley stripe mosaic virus virions.

    Directory of Open Access Journals (Sweden)

    Valentin V Makarov

    Full Text Available Virions of Barley stripe mosaic virus (BSMV were neglected for more than thirty years after their basic properties were determined. In this paper, the physicochemical characteristics of BSMV virions and virion-derived viral capsid protein (CP were analyzed, namely, the absorption and intrinsic fluorescence spectra, circular dichroism spectra, differential scanning calorimetry curves, and size distributions by dynamic laser light scattering. The structural properties of BSMV virions proved to be intermediate between those of Tobacco mosaic virus (TMV, a well-characterized virus with rigid rod-shaped virions, and flexuous filamentous plant viruses. The BSMV virions were found to be considerably more labile than expected from their rod-like morphology and a distant sequence relation of the BSMV and TMV CPs. The circular dichroism spectra of BSMV CP subunits incorporated into the virions, but not subunits of free CP, demonstrated a significant proportion of beta-structure elements, which were proposed to be localized mostly in the protein regions exposed on the virion outer surface. These beta-structure elements likely formed during virion assembly can comprise the N- and C-terminal protein regions unstructured in the non-virion CP and can mediate inter-subunit interactions. Based on computer-assisted structure modeling, a model for BSMV CP subunit structural fold compliant with the available experimental data was proposed.

  14. Transmission Electron Microscopy Studies of Cellular Responses to Entry of Virions: One Kind of Natural Nanobiomaterial

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    Zheng Liu

    2012-01-01

    Full Text Available Virions are one kind of nanoscale pathogen and are able to infect living cells of animals, plants, and bacteria. The infection is an intrinsic property of the virions, and the biological process provides a good model for studying how these nanoparticles enter into cells. During the infection, the viruses employ different strategies to which the cells have developed respective responses. For this paper, we chose Bombyx mori cypovirus 1 (BmCPV-1 interactions with midgut cells from silkworm, and severe acute respiratory syndrome (SARS associated coronavirus interactions with Vero E6 cells, as examples to demonstrate the response of eukaryotic cells to two different types of virus from our previous studies. The bacteriophage-bacteria interactions are also introduced to elucidate how the bacteriophage conquers the barrier of cell walls in the prokaryotic cells to transport genome into the host.

  15. Characterization of the Determinants of NS2-3-Independent Virion Morphogenesis of Pestiviruses.

    Science.gov (United States)

    Klemens, O; Dubrau, D; Tautz, N

    2015-11-01

    , nonstructural protein NS2-3 is of critical importance to switch between these processes. While free NS3 is essential for RNA replication, uncleaved NS2-3, which accumulates over time in the infected cell, is required for virion morphogenesis. In contrast, the virion morphogenesis of the related hepatitis C virus is independent from uncleaved NS2-NS3. Here, we demonstrate that pestiviruses can adapt to virion morphogenesis in the absence of uncleaved NS2-3 by just two amino acid exchanges. While the mechanism behind this gain of function remains elusive, the fact that it can be achieved by such minor changes is in line with the assumption that an ancestral virus already used this mechanism but lost it in the course of adapting to a new host/infection strategy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. In a nutshell: structure and assembly of the vaccinia virion.

    Science.gov (United States)

    Condit, Richard C; Moussatche, Nissin; Traktman, Paula

    2006-01-01

    Poxviruses comprise a large family of viruses characterized by a large, linear dsDNA genome, a cytoplasmic site of replication and a complex virion morphology. The most notorious member of the poxvirus family is variola, the causative agent of smallpox. The laboratory prototype virus used for the study of poxviruses is vaccinia, the virus that was used as a live, naturally attenuated vaccine for the eradication of smallpox. Both the morphogenesis and structure of poxvirus virions are unique among viruses. Poxvirus virions apparently lack any of the symmetry features common to other viruses such as helical or icosahedral capsids or nucleocapsids. Instead poxvirus virions appear as "brick shaped" or "ovoid" membrane-bound particles with a complex internal structure featuring a walled, biconcave core flanked by "lateral bodies." The virion assembly pathway involves a remarkable fabrication of membrane-containing crescents and immature virions, which evolve into mature virions in a process that is unparalleled in virology. As a result of significant advances in poxvirus genetics and molecular biology during the past 15 years, we can now positively identify over 70 specific gene products contained in poxvirus virions, and we can describe the effects of mutations in over 50 specific genes on poxvirus assembly. This review summarizes these advances and attempts to assemble them into a comprehensible and thoughtful picture of poxvirus structure and assembly.

  17. 46 CFR 154.540 - Quick-closing shut-off valves: Emergency shut-down system.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Quick-closing shut-off valves: Emergency shut-down... shut-down system. The quick-closing shut-off valves under §§ 154.530, 154.532, and 154.538 must have an emergency shut-down system that: (a) Closes all the valves; (b) Is actuated by a single control in at least...

  18. UV-Sensitivity of Shiga Toxin-Converting Bacteriophage Virions Φ24B, 933W, P22, P27 and P32

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    Sylwia Bloch

    2015-09-01

    Full Text Available Shiga toxin-converting bacteriophages (Stx phages are present as prophages in Shiga toxin-producing Escherichia coli (STEC strains. Theses phages can be transmitted to previously non-pathogenic E. coli cells making them potential producers of Shiga toxins, as they bear genes for these toxins in their genomes. Therefore, sensitivity of Stx phage virions to various conditions is important in both natural processes of spreading of these viruses and potential prophylactic control of appearance of novel pathogenic E. coli strains. In this report we provide evidence that virions of Stx phages are significantly more sensitive to UV irradiation than bacteriophage λ. Following UV irradiation of Stx virions at the dose of 50 J/m2, their infectivity dropped by 1–3 log10, depending on the kind of phage. Under these conditions, a considerable release of phage DNA from virions was observed, and electron microscopy analyses indicated a large proportion of partially damaged virions. Infection of E. coli cells with UV-irradiated Stx phages resulted in significantly decreased levels of expression of N and cro genes, crucial for lytic development. We conclude that inactivation of Stx virions caused by relatively low dose of UV light is due to damage of capsids that prevents effective infection of the host cells.

  19. Host transcript accumulation during lytic KSHV infection reveals several classes of host responses.

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    Sanjay Chandriani

    Full Text Available Lytic infection by Kaposi's sarcoma-associated herpesvirus (KSHV is associated with an extensive shutoff of host gene expression, mediated chiefly by accelerated mRNA turnover due to expression of the viral SOX protein. We have previously identified a small number of host mRNAs that can escape SOX-mediated degradation. Here we present a detailed, transcriptome-wide analysis of host shutoff, with careful microarray normalization to allow rigorous determination of the magnitude and extent of transcript loss. We find that the extent of transcript reduction represents a continuum of susceptibilities of transcripts to virus-mediated shutoff. Our results affirm that the levels of over 75% of host transcripts are substantially reduced during lytic infection, but also show that another approximately 20% of cellular mRNAs declines only slightly (less than 2-fold during the course of infection. Approximately 2% of examined cellular genes are strongly upregulated during lytic infection, most likely due to transcriptional induction of mRNAs that display intrinsic SOX-resistance.

  20. Single-virion sequencing of lamivudine-treated HBV populations reveal population evolution dynamics and demographic history.

    Science.gov (United States)

    Zhu, Yuan O; Aw, Pauline P K; de Sessions, Paola Florez; Hong, Shuzhen; See, Lee Xian; Hong, Lewis Z; Wilm, Andreas; Li, Chen Hao; Hue, Stephane; Lim, Seng Gee; Nagarajan, Niranjan; Burkholder, William F; Hibberd, Martin

    2017-10-27

    Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients - once before antiviral treatment and once after viral rebound due to resistance. With single-virion sequencing, we obtained 248-8796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently through PacBio SMRT and Illumina Pooled deep sequencing. Overall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance and host adaptation, allows differentiation between soft or hard selective sweeps, and may be useful in the reconstruction of intra-host viral population demographic history.

  1. Proteomic analysis of the herpes simplex virus 1 virion protein 16 transactivator protein in infected cells.

    Science.gov (United States)

    Suk, Hyung; Knipe, David M

    2015-06-01

    The herpes simplex virus 1 virion protein 16 (VP16) tegument protein forms a transactivation complex with the cellular proteins host cell factor 1 (HCF-1) and octamer-binding transcription factor 1 (Oct-1) upon entry into the host cell. VP16 has also been shown to interact with a number of virion tegument proteins and viral glycoprotein H to promote viral assembly, but no comprehensive study of the VP16 proteome has been performed at early times postinfection. We therefore performed a proteomic analysis of VP16-interacting proteins at 3 h postinfection. We confirmed the interaction of VP16 with HCF-1 and a large number of cellular Mediator complex proteins, but most surprisingly, we found that the major viral protein associating with VP16 is the infected cell protein 4 (ICP4) immediate-early (IE) transactivator protein. These results raise the potential for a new function for VP16 in associating with the IE ICP4 and playing a role in transactivation of early and late gene expression, in addition to its well-documented function in transactivation of IE gene expression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Human cytomegalovirus exploits interferon-induced transmembrane proteins to facilitate morphogenesis of the virion assembly compartment.

    Science.gov (United States)

    Xie, Maorong; Xuan, Baoqin; Shan, Jiaoyu; Pan, Deng; Sun, Yamei; Shan, Zhao; Zhang, Jinping; Yu, Dong; Li, Bin; Qian, Zhikang

    2015-03-01

    Recently, interferon-induced transmembrane proteins (IFITMs) have been identified to be key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and knockdown of IFITMs by RNA interference reduced the virus titer by about 100-fold on day 8 postinfection, according to the findings of a virus yield assay at a low multiplicity of infection. Virus gene expression and DNA synthesis were not affected, but the typical round structure of the vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is closely related to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication. HCMV is known to repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication. Our results expand the range of ISGs that can be exploited by HCMV for its replication. This is also the first report of a proviral function of IFITMs in DNA virus replication. In addition, whereas previous studies showed that IFITMs modulate virus entry, which is a very early stage in the virus life cycle, we identified a new

  3. Incorporation of Spike and Membrane Glycoproteins into Coronavirus Virions

    Science.gov (United States)

    Ujike, Makoto; Taguchi, Fumihiro

    2015-01-01

    The envelopes of coronaviruses (CoVs) contain primarily three proteins; the two major glycoproteins spike (S) and membrane (M), and envelope (E), a non-glycosylated protein. Unlike other enveloped viruses, CoVs bud and assemble at the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). For efficient virion assembly, these proteins must be targeted to the budding site and to interact with each other or the ribonucleoprotein. Thus, the efficient incorporation of viral envelope proteins into CoV virions depends on protein trafficking and protein–protein interactions near the ERGIC. The goal of this review is to summarize recent findings on the mechanism of incorporation of the M and S glycoproteins into the CoV virion, focusing on protein trafficking and protein–protein interactions. PMID:25855243

  4. HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions

    OpenAIRE

    Qi, Qianqian; Wang, Qian; Chen, Weizao; Du, Lanying; Dimitrov, Dimiter S; Lu, Lu; Jiang, Shibo

    2017-01-01

    Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or ...

  5. Antigenic properties of the human immunodeficiency virus envelope glycoprotein gp120 on virions bound to target cells.

    Directory of Open Access Journals (Sweden)

    Meron Mengistu

    2015-03-01

    Full Text Available The HIV-1 envelope glycoprotein, gp120, undergoes multiple molecular interactions and structural rearrangements during the course of host cell attachment and viral entry, which are being increasingly defined at the atomic level using isolated proteins. In comparison, antigenic markers of these dynamic changes are essentially unknown for single HIV-1 particles bound to target cells. Such markers should indicate how neutralizing and/or non-neutralizing antibodies might interdict infection by either blocking infection or sensitizing host cells for elimination by Fc-mediated effector function. Here we address this deficit by imaging fluorescently labeled CCR5-tropic HIV-1 pseudoviruses using confocal and superresolution microscopy to track the exposure of neutralizing and non-neutralizing epitopes as they appear on single HIV-1 particles bound to target cells. Epitope exposure was followed under conditions permissive or non-permissive for viral entry to delimit changes associated with virion binding from those associated with post-attachment events. We find that a previously unexpected array of gp120 epitopes is exposed rapidly upon target cell binding. This array comprises both neutralizing and non-neutralizing epitopes, the latter being hidden on free virions yet capable of serving as potent targets for Fc-mediated effector function. Under non-permissive conditions for viral entry, both neutralizing and non-neutralizing epitope exposures were relatively static over time for the majority of bound virions. Under entry-permissive conditions, epitope exposure patterns changed over time on subsets of virions that exhibited concurrent variations in virion contents. These studies reveal that bound virions are distinguished by a broad array of both neutralizing and non-neutralizing gp120 epitopes that potentially sensitize a freshly engaged target cell for destruction by Fc-mediated effector function and/or for direct neutralization at a post-binding step

  6. Mechanism of Human Influenza Virus RNA Persistence and Virion Survival in Feces: Mucus Protects Virions From Acid and Digestive Juices.

    Science.gov (United States)

    Hirose, Ryohei; Nakaya, Takaaki; Naito, Yuji; Daidoji, Tomo; Watanabe, Yohei; Yasuda, Hiroaki; Konishi, Hideyuki; Itoh, Yoshito

    2017-07-01

    Although viral RNA or infectious virions have been detected in the feces of individuals infected with human influenza A and B viruses (IAV/IBV), the mechanism of viral survival in the gastrointestinal tract remains unclear. We developed a model that attempts to recapitulate the conditions encountered by a swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices (gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA and virions, allowing the virus to retain its infectivity. Our results suggest that virions and RNA present in swallowed mucus are not inactivated or degraded by the gastrointestinal environment, allowing their detection in feces. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  7. Virion-targeted viral inactivation: new therapy against viral infection.

    Science.gov (United States)

    Okui, N; Kitamura, Y; Kobayashi, N; Sakuma, R; Ishikawa, T; Kitamura, T

    2001-01-01

    Acquired immune deficiency syndrome (AIDS) is resistant to all current therapy. Gene therapy is an attractive alternative or additive to current, unsatisfactory AIDS therapy. To develop an antiviral molecule targeting viral integrase (HIV IN), we generated a single-chain antibody, termed scAb, which interacted with human immunodeficiency virus type 1 (HIV-1) IN and inhibited virus replication at the integration step when expressed intracellularly. To reduce infectivity from within the virus particles, we made expression plasmids (pC-scAbE-Vpr, pC-scAbE-CA, and pC-scAbE-WXXF), which expressed the anti-HIV IN scAb fused to the N-terminus of HIV-1-associated accessory protein R (Vpr), capsid protein (CA), and specific binding motif to Vpr (WXXF), respectively. All fusion proteins were tagged with a nine-amino acid peptide derived from influenza virus hemagglutinin (HA) at the C terminus. The fusion molecules, termed scAbE-Vpr, scAbE-CA, and scAbE-WXXF, interacted specifically with HIV IN immobilized on a nitrocellulose membrane. Immunoblot analysis showed that scAbE-Vpr, scAbE-CA, and scAbE-WXXF were incorporated into the virions produced by cotransfection of 293T cells with HIV-1 infectious clone DNA (pLAI) and pC-scAbE-Vpr, pC-scAbE-WXXF. A multinuclear activation galactosidase indicator (MAGI) assay revealed that the virions released from 293T cells cotransfected with pLAI and pC-scAbE-Vpr, pC-scAbE-WXXF had as little 1000-fold of the infectivity of the control wild-type virions, which were produced from the 293T cells transfected with pLAI alone. Furthermore, the virions produced from the 293T cells cotransfected with pLAI and an scAb expression vector (pC-scAb) showed only 1% of the infectivity of the control HIV-1 in a MAGI assay, although scAb was not incorporated into the virions. In either instance, the total quantity of the progeny virions released from the transfected 293T cells and the patterns of the virion proteins were hardly affected by the presence of

  8. Properties of virion transactivator proteins encoded by primate cytomegaloviruses

    Directory of Open Access Journals (Sweden)

    Barry Peter A

    2009-05-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1 genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action. Results The UL82 homolog encoded by simian cytomegalovirus (SCMV, strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All

  9. Native hepatitis B virions and capsids visualized by electron cryomicroscopy.

    Science.gov (United States)

    Dryden, Kelly A; Wieland, Stefan F; Whitten-Bauer, Christina; Gerin, John L; Chisari, Francis V; Yeager, Mark

    2006-06-23

    Hepatitis B virus (HBV) infects more than 350 million people, of which one million will die every year. The infectious virion is an enveloped capsid containing the viral polymerase and double-stranded DNA genome. The structure of the capsid assembled in vitro from expressed core protein has been studied intensively. However, little is known about the structure and assembly of native capsids present in infected cells, and even less is known about the structure of mature virions. We used electron cryomicroscopy (cryo-EM) and image analysis to examine HBV virions (Dane particles) isolated from patient serum and capsids positive and negative for HBV DNA isolated from the livers of transgenic mice. Both types of capsids assembled as icosahedral particles indistinguishable from previous image reconstructions of capsids. Likewise, the virions contained capsids with either T = 3 or T = 4 icosahedral symmetry. Projections extending from the lipid envelope were attributed to surface glycoproteins. Their packing was unexpectedly nonicosahedral but conformed to an ordered lattice. These structural features distinguish HBV from other enveloped viruses.

  10. Microplitis demolitor bracovirus genome segments vary in abundance and are individually packaged in virions.

    Science.gov (United States)

    Beck, Markus H; Inman, Ross B; Strand, Michael R

    2007-03-01

    Polydnaviruses (PDVs) are distinguished by their unique association with parasitoid wasps and their segmented, double-stranded (ds) DNA genomes that are non-equimolar in abundance. Relatively little is actually known, however, about genome packaging or segment abundance of these viruses. Here, we conducted electron microscopy (EM) and real-time polymerase chain reaction (PCR) studies to characterize packaging and segment abundance of Microplitis demolitor bracovirus (MdBV). Like other PDVs, MdBV replicates in the ovaries of females where virions accumulate to form a suspension called calyx fluid. Wasps then inject a quantity of calyx fluid when ovipositing into hosts. The MdBV genome consists of 15 segments that range from 3.6 (segment A) to 34.3 kb (segment O). EM analysis indicated that MdBV virions contain a single nucleocapsid that encapsidates one circular DNA of variable size. We developed a semi-quantitative real-time PCR assay using SYBR Green I. This assay indicated that five (J, O, H, N and B) segments of the MdBV genome accounted for more than 60% of the viral DNAs in calyx fluid. Estimates of relative segment abundance using our real-time PCR assay were also very similar to DNA size distributions determined from micrographs. Analysis of parasitized Pseudoplusia includens larvae indicated that copy number of MdBV segments C, B and J varied between hosts but their relative abundance within a host was virtually identical to their abundance in calyx fluid. Among-tissue assays indicated that each viral segment was most abundant in hemocytes and least abundant in salivary glands. However, the relative abundance of each segment to one another was similar in all tissues. We also found no clear relationship between MdBV segment and transcript abundance in hemocytes and fat body.

  11. Shut-Off Valves of Electric Drive with Thyristor Voltage Regulators and Software Implementation of the Indirect Determination of Moment

    Directory of Open Access Journals (Sweden)

    Vlasov Anton I.

    2017-01-01

    Full Text Available In this paper we consider the shut-off valve of electric drive with thyristor voltage regulator and microprocessor control which ensures a constant indirect control of torque value on the electric drive as well as its limitation in the case of the creation of an emergency on the main oil pipeline. It was found that the use of the integrated microprocessor control systems with software implementation calculating of given torque in the system of induction motor - thyristor voltage regulator, allows you to get the best performance of electric drive shut-off valve with the restrictions on the maximum current, torque whith deviations of voltage parameters and improve the safety of the process of oil pumping.

  12. HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions.

    Science.gov (United States)

    Qi, Qianqian; Wang, Qian; Chen, Weizao; Du, Lanying; Dimitrov, Dimiter S; Lu, Lu; Jiang, Shibo

    2017-06-21

    Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT). HIV-1 virions were separated from the inhibitors using PEG-6000, followed by testing of the residual infectivity of the HIV-1 virions. 2Dm2m and 4Dm2m exhibited significant inactivation activity against all HIV-1 strains tested with EC50 values at the low nanomolar level, whereas none of the gp41-targeting peptides showed inactivation activity at concentrations up to 250 nM. Notably, these three peptides significantly enhanced protein-mediated inactivation against cell-free HIV-1 virions, including HIV-1 laboratory-adapted and primary HIV-1 strains, as well as those resistant to T20 or T2635 and virions released from reactivated latently HIV-1-infected cells. These results indicate that the gp120-targeting bispecific multivalent proteins 2Dm2m and 4Dm2m have potential for further development as HIV-1 inactivator-based antiviral drugs for use in the clinic, either alone or in combination with a gp41-targeting HIV-1 fusion inhibitor such as T20, to treat patients with HIV-1 infection and AIDS.

  13. Modeling and analysis of hydraulic dashpot for impact free operation in a shut-off rod drive mechanism

    Directory of Open Access Journals (Sweden)

    Narendra K. Singh

    2016-09-01

    Full Text Available Rotary hydraulic dashpot used for shut-off rod drive mechanism application of a nuclear reactor has been studied in this paper for impact free operation. The rotary hydraulic dashpot has been modeled as a system with 1 degree of freedom (DOF and the simulation results are experimentally validated. The dashpot is modeled as a hinge joint with moving and fixed vanes as rigid bodies. Shut-off rods are used to shut-down a nuclear reactor and hydraulic dashpot absorbs the energy of freely falling shut-off rod at the end of rod travel. With the increase in the environmental temperature the dashpot becomes underdamped at a point because of reduction in the viscosity of oil and results into impact on mechanism components. Hydraulic dashpot designs are finalized with an optimum combination of dashpot clearances and oil viscosity to meet the drop time criterion and impact free operation at room temperature as well as at elevated temperature. Also with the change in mechanical loads the dashpot becomes underdamped. So the study is further extended to see the effects of various parameters such as moment of inertia, constraint angle and applied moment on the dashpot. Study is focused on obtaining dashpot responses in terms of relative rotation, relative angular velocity and relative angular acceleration at various environmental temperatures. Finite element commercial code COMSOL Multiphysics 5.1 has been used for numerical simulations. Equations for both rigid body dynamics and heat transfer in solids are solved simultaneously. Thus, energy absorbed and local temperature rise in the dashpot operation is also obtained. Both simulation and experimental results at wide range of environmental temperature are presented and compared in this paper. This study forms a good tool to design a hydraulic dashpot, which gives impact free operation in a shut-off rod free fall.

  14. Dense Array of Spikes on HIV-1 Virion Particles.

    Science.gov (United States)

    Stano, Armando; Leaman, Daniel P; Kim, Arthur S; Zhang, Lei; Autin, Ludovic; Ingale, Jidnyasa; Gift, Syna K; Truong, Jared; Wyatt, Richard T; Olson, Arthur J; Zwick, Michael B

    2017-07-15

    HIV-1 is rare among viruses for having a low number of envelope glycoprotein (Env) spikes per virion, i.e., ∼7 to 14. This exceptional feature has been associated with avoidance of humoral immunity, i.e., B cell activation and antibody neutralization. Virus-like particles (VLPs) with increased density of Env are being pursued for vaccine development; however, these typically require protein engineering that alters Env structure. Here, we used instead a strategy that targets the producer cell. We employed fluorescence-activated cell sorting (FACS) to sort for cells that are recognized by trimer cross-reactive broadly neutralizing antibody (bnAb) and not by nonneutralizing antibodies. Following multiple iterations of FACS, cells and progeny virions were shown to display higher levels of antigenically correct Env in a manner that correlated between cells and cognate virions (P = 0.027). High-Env VLPs, or hVLPs, were shown to be monodisperse and to display more than a 10-fold increase in spikes per particle by electron microscopy (average, 127 spikes; range, 90 to 214 spikes). Sequencing revealed a partial truncation in the C-terminal tail of Env that had emerged in the sort; however, iterative rounds of "cell factory" selection were required for the high-Env phenotype. hVLPs showed greater infectivity than standard pseudovirions but largely similar neutralization sensitivity. Importantly, hVLPs also showed superior activation of Env-specific B cells. Hence, high-Env HIV-1 virions, obtained through selection of producer cells, represent an adaptable platform for vaccine design and should aid in the study of native Env.IMPORTANCE The paucity of spikes on HIV is a unique feature that has been associated with evasion of the immune system, while increasing spike density has been a goal of vaccine design. Increasing the density of Env by modifying it in various ways has met with limited success. Here, we focused instead on the producer cell. Cells that stably express HIV

  15. Proteomic analysis of the EhV-86 virion

    OpenAIRE

    Lilley Kathryn S; Howard Julie A; Allen Michael J; Wilson William H

    2008-01-01

    Abstract Background Emiliania huxleyi virus 86 (EhV-86) is the type species of the genus Coccolithovirus within the family Phycodnaviridae. The fully sequenced 407,339 bp genome is predicted to encode 473 protein coding sequences (CDSs) and is the largest Phycodnaviridae sequenced to date. The majority of EhV-86 CDSs exhibit no similarity to proteins in the public databases. Results Proteomic analysis by 1-DE and then LC-MS/MS determined that the virion of EhV-86 is composed of at least 28 pr...

  16. Identification of the bacteriophage T4 unf ( = alc) gene product, a protein involved in the shutoff of host transcription.

    Science.gov (United States)

    Herman, R E; Haas, N; Snustad, D P

    1984-10-01

    The introduction of plasmid pR386 into E. coli cells renders them restrictive to the growth of phage T4 unf ( = alc) mutants. This system has been used to isolate Unf+ revertants, which, along with the mutant parental strains, have been used to identify the unf gene product by two-dimensional gel electrophoresis. Synthesis of the unf gene product, a polypeptide of just over 18,000 daltons in size, begins within 1 min after infection and terminates at about 12 min after infection at 30 degrees. Gene dosage experiments suggest that the unf protein functions catalytically.

  17. Subcellular Localization of HIV-1 gag-pol mRNAs Regulates Sites of Virion Assembly.

    Science.gov (United States)

    Becker, Jordan T; Sherer, Nathan M

    2017-03-15

    -1) virus particles at the plasma membrane (PM). Artificially tethering viral mRNAs encoding Gag capsid proteins (gag-pol mRNAs) to distinct non-PM subcellular locales, such as cytoplasmic vesicles or the actin cytoskeleton, markedly alters Gag subcellular distribution, relocates sites of assembly, and reduces net virus particle production. These observations support a model for native HIV-1 assembly wherein HIV-1 gag-pol mRNA localization helps to confine interactions between Gag, viral RNAs, and host determinants in order to ensure virion production at the right place and right time. Direct perturbation of HIV-1 mRNA subcellular localization may represent a novel antiviral strategy. Copyright © 2017 American Society for Microbiology.

  18. Rapid shut-off and burial of slope channel-levee systems: new imaging and analysis of the Rio Grande submarine fan

    Science.gov (United States)

    Swartz, J. M.; Mohrig, D. C.; Gulick, S. P. S.; Stockli, D. F.; Daniller-Varghese, M. S.; Fernandez, R.

    2016-12-01

    The continental slope of the western Gulf of Mexico is host to a major depositional system, the Rio Grande Fan. Unlike many submarine fans, the surface of the Rio Grande Fan lacks large submarine channels and associated levees. Prior analysis of continental shelf stratigraphy has identified the presence of past extensive shelf-edge delta systems, when the Rio Grande River system flowed across the modern shelf and delivered high volumes of sediment to the shelf/slope break. A major gap in understanding this system is how large volumes of sediment, particularly sands, are transported from the shelf edge systems down the slope and onto the basin-floor fan without constructional channel-levee systems. Over 500km of new high-resolution 2D multichannel seismic (MCS) and CHIRP echosounder data were collected over the shelf edge and upper slope of the Rio Grande fan. These new data provide unprecedented imaging of the shelf-edge delta systems and associated slope deposits. Our preliminary observations indicate that while the modern seafloor morphology of the fan is dominated by mass-transport deposits, slumps and minor inactive channels, buried below thick mud deposits are very large aggradational channels-levee systems. These systems have channel belts almost 1km wide, with confining levees that approach 10km in width. The main body of the fan is built from these channel complexes, which appear to have then rapidly buried in mud. We document the evolution, from initial channelization to burial, of these massive slope systems. Regional correlation suggests that this most recent episode of channel-levee growth and shutoff occurred very rapidly, and could indicate drastically higher sediment flux through the paleo-Rio Grande River than that of the modern. Our results highlight an example of a slope-channel system that is subject to significant variations in sediment supply. Such systems can apparently build large late Pleistocene submarine fan deposits that can be difficult

  19. Capillarity-induced disassembly of virions in carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Fan Xiaobin; Peng Wenchao; Li Yang; Li Xianyu; Zhang Guoliang; Zhang Fengbao [School of Chemical Engineering and Technology, Tianjin University, Tianjin (China); Barclay, J Elaine; Evans, David J [Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH (United Kingdom)], E-mail: fbzhang@tju.edu.cn

    2008-04-23

    Studying the transport and fate of viruses through nanochannels is of great importance. By using the nanochannel of a carbon nanotube (CNT) as an ideal model, we evaluated the possibility of capillarity-induced viral transport through a closely fitting nanochannel and explored the mechanisms involved. It is shown both experimentally and theoretically that Cowpea mosaic virus can enter CNTs by capillarity. However, when introduced into a nanotube the protein capsid may disassemble. During the initial capillary filling stage, anomalous needle-shaped high pressure exists in the centre of the nanotube's entrance. This high pressure, combining with the significant negative pressure within the nanotube, may account for the disassembly of the virions.

  20. Fusion between perinuclear virions and the outer nuclear membrane requires the fusogenic activity of herpes simplex virus gB.

    Science.gov (United States)

    Wright, Catherine C; Wisner, Todd W; Hannah, Brian P; Eisenberg, Roselyn J; Cohen, Gary H; Johnson, David C

    2009-11-01

    Herpesviruses cross nuclear membranes (NMs) in two steps, as follows: (i) capsids assemble and bud through the inner NM into the perinuclear space, producing enveloped virus particles, and (ii) the envelopes of these virus particles fuse with the outer NM. Two herpes simplex virus (HSV) glycoproteins, gB and gH (the latter, likely complexed as a heterodimer with gL), are necessary for the second step of this process. Mutants lacking both gB and gH accumulate in the perinuclear space or in herniations (membrane vesicles derived from the inner NM). Both gB and gH/gL are also known to act directly in fusing the virion envelope with host cell membranes during HSV entry into cells, i.e., both glycoproteins appear to function directly in different aspects of the membrane fusion process. We hypothesized that HSV gB and gH/gL also act directly in the membrane fusion that occurs during virus egress from the nucleus. Previous studies of the role of gB and gH/gL in nuclear egress involved HSV gB and gH null mutants that could potentially also possess gross defects in the virion envelope. Here, we produced recombinant HSV-expressing mutant forms of gB with single amino acid substitutions in the hydrophobic "fusion loops." These fusion loops are thought to play a direct role in membrane fusion by insertion into cellular membranes. HSV recombinants expressing gB with any one of four fusion loop mutations (W174R, W174Y, Y179K, and A261D) were unable to enter cells. Moreover, two of the mutants, W174Y and Y179K, displayed reduced abilities to mediate HSV cell-to-cell spread, and W174R and A261D exhibited no spread. All mutant viruses exhibited defects in nuclear egress, enveloped virions accumulated in herniations and in the perinuclear space, and fewer enveloped virions were detected on cell surfaces. These results support the hypothesis that gB functions directly to mediate the fusion between perinuclear virus particles and the outer NM.

  1. Parvoviral host range and cell entry mechanisms.

    Science.gov (United States)

    Cotmore, Susan F; Tattersall, Peter

    2007-01-01

    Parvoviruses elaborate rugged nonenveloped icosahedral capsids of approximately 260 A in diameter that comprise just 60 copies of a common core structural polypeptide. While serving as exceptionally durable shells, capable of protecting the single-stranded DNA genome from environmental extremes, the capsid also undergoes sequential conformational changes that allow it to translocate the genome from its initial host cell nucleus all the way into the nucleus of its subsequent host. Lacking a duplex transcription template, the virus must then wait for its host to enter S-phase before it can initiate transcription and usurp the cell's synthetic pathways. Here we review cell entry mechanisms used by parvoviruses. We explore two apparently distinct modes of host cell specificity, first that used by Minute virus of mice, where subtle glycan-specific interactions between host receptors and residues surrounding twofold symmetry axes on the virion surface mediate differentiated cell type target specificity, while the second involves novel protein interactions with the canine transferrin receptor that allow a mutant of the feline leukopenia serotype, Canine parvovirus, to bind to and infect dog cells. We then discuss conformational shifts in the virion that accompany cell entry, causing exposure of a capsid-tethered phospholipase A2 enzymatic core that acts as an endosomolytic agent to mediate virion translocation across the lipid bilayer into the cell cytoplasm. Finally, we discuss virion delivery into the nucleus, and consider the nature of transcriptionally silent DNA species that, escaping detection by the cell, might allow unhampered progress into S-phase and hence unleash the parvoviral Trojan horse.

  2. The vaccinia virus E6 protein influences virion protein localization during virus assembly

    Energy Technology Data Exchange (ETDEWEB)

    Condit, Richard C., E-mail: condit@mgm.ufl.edu; Moussatche, Nissin

    2015-08-15

    Vaccinia virus mutants in which expression of the virion core protein gene E6R is repressed are defective in virion morphogenesis. E6 deficient infections fail to properly package viroplasm into viral membranes, resulting in an accumulation of empty immature virions and large aggregates of viroplasm. We have used immunogold electron microscopy and immunofluorescence confocal microscopy to assess the intracellular localization of several virion structural proteins and enzymes during E6R mutant infections. We find that during E6R mutant infections virion membrane proteins and virion transcription enzymes maintain a normal localization within viral factories while several major core and lateral body proteins accumulate in aggregated virosomes. The results support a model in which vaccinia virions are assembled from at least three substructures, the membrane, the viroplasm and a “pre-nucleocapsid”, and that the E6 protein is essential for maintaining proper localization of the seven-protein complex and the viroplasm during assembly. - Highlights: • Mutation of E6 disrupts association of viral membranes with viral core proteins • Mutation of E6 does not perturb viral membrane biosynthesis • Mutation of E6 does not perturb localization of viral transcription enzymes • Mutation of E6 causes mis-localization and aggregation of viral core proteins • Vaccinia assembly uses three subassemblies: membranes, viroplasm, prenucleocapsid.

  3. Architects of assembly: roles of Flaviviridae non-structural proteins in virion morphogenesis.

    Science.gov (United States)

    Murray, Catherine L; Jones, Christopher T; Rice, Charles M

    2008-09-01

    Viruses of the Flaviviridae family, including hepatitis C, dengue and bovine viral diarrhoea, are responsible for considerable morbidity and mortality worldwide. Recent advances in our understanding of virion assembly have uncovered commonalities among distantly related members of this family. We discuss the emerging hypothesis that physical virion components are not alone in forming the infectious particle, but that non-structural proteins are intimately involved in orchestrating morphogenesis. Pinpointing the roles of Flaviviridae proteins in virion production could reveal new avenues for antiviral therapeutics.

  4. y Human herpesvirus 6 envelope components enriched in lipid rafts: evidence for virion-associated lipid rafts

    Directory of Open Access Journals (Sweden)

    Yamanishi Koichi

    2009-08-01

    Full Text Available Abstract In general, enveloped viruses are highly dependent on their lipid envelope for entry into host cells. Here, we demonstrated that during the course of virus maturation, a significant proportion of human herpesvirus 6 (HHV-6 envelope proteins were selectively concentrated in the detergent-resistant glycosphingolipid- and cholesterol-rich membranes (rafts in HHV-6-infected cells. In addition, the ganglioside GM1, which is known to partition preferentially into lipid rafts, was detected in purified virions, along with viral envelope glycoproteins, gH, gL, gB, gQ1, gQ2 and gO indicating that at least one raft component was included in the viral particle during the assembly process.

  5. Mapping the small RNA content of simian immunodeficiency virions (SIV.

    Directory of Open Access Journals (Sweden)

    Markus Brameier

    Full Text Available Recent evidence indicates that regulatory small non-coding RNAs are not only components of eukaryotic cells and vesicles, but also reside within a number of different viruses including retroviral particles. Using ultra-deep sequencing we have comprehensively analyzed the content of simian immunodeficiency virions (SIV, which were compared to mock-control preparations. Our analysis revealed that more than 428,000 sequence reads matched the SIV mac239 genome sequence. Among these we could identify 12 virus-derived small RNAs (vsRNAs that were highly abundant. Beside known retrovirus-enriched small RNAs, like 7SL-RNA, tRNA(Lys3 and tRNA(Lys isoacceptors, we also identified defined fragments derived from small ILF3/NF90-associated RNA snaR-A14, that were enriched more than 50 fold in SIV. We also found evidence that small nucleolar RNAs U2 and U12 were underrepresented in the SIV preparation, indicating that the relative number or the content of co-isolated exosomes was changed upon infection. Our comprehensive atlas of SIV-incorporated small RNAs provides a refined picture of the composition of retrovirions, which gives novel insights into viral packaging.

  6. Quantitative real-time single particle analysis of virions

    Energy Technology Data Exchange (ETDEWEB)

    Heider, Susanne; Metzner, Christoph, E-mail: christoph.metzner@vetmeduni.ac.at

    2014-08-15

    Providing information about single virus particles has for a long time been mainly the domain of electron microscopy. More recently, technologies have been developed—or adapted from other fields, such as nanotechnology—to allow for the real-time quantification of physical virion particles, while supplying additional information such as particle diameter concomitantly. These technologies have progressed to the stage of commercialization increasing the speed of viral titer measurements from hours to minutes, thus providing a significant advantage for many aspects of virology research and biotechnology applications. Additional advantages lie in the broad spectrum of virus species that may be measured and the possibility to determine the ratio of infectious to total particles. A series of disadvantages remain associated with these technologies, such as a low specificity for viral particles. In this review we will discuss these technologies by comparing four systems for real-time single virus particle analysis and quantification. - Highlights: • We introduce four methods for virus particle-based quantification of viruses. • They allow for quantification of a wide range of samples in under an hour time. • The additional measurement of size and zeta potential is possible for some.

  7. Integration of Polydnavirus DNA into Host Cellular Genomic DNA

    Science.gov (United States)

    Polydnaviruses are unique insect viruses that are obligately associated with thousands of parasitoid wasp species in intimate mutualistic symbioses. Whereas most cases of virus infection of host cells leads to production of progeny virions, polydnaviruses have evolved by atypical lifecycle and repli...

  8. Studies of archaeal virus-host systems in thermal environments

    DEFF Research Database (Denmark)

    Erdmann, Susanne

    features. Most of the isolated archaeal viruses infecting members of the Crenarchaeota have been characterized regarding their genome, the structure of their virions and their influence on the host viability. Only a few, SIRV a rod-shaped and STIV an icosahedrical virus, have been subjected to more...

  9. Human Papillomavirus (HPV) virion induced cancer and subfertility, two sides of the same coin.

    Science.gov (United States)

    Depuydt, C E; Beert, J; Bosmans, E; Salembier, G

    2016-12-01

    In the natural history of HPV infections, the HPV virions can induce two different pathways, namely the infec- tious virion producing pathway and the clonal transforming pathway. An overview is given of the burden that is associated with HPV infections that can both lead to cervical cancer and/or temporal subfertility. That HPV infections cause serious global health burden due to HPV-associated cancers is common knowledge, but that it is also responsible for a substantial part of idiopathic subfertility is greatly underestimated. The bulk of the detected HPV DNA whether in men or women is however infectious from origin. Because the dissociation between HPV viruses and HPV virions or infection and disease remains difficult for clinicians as well as for HPV detection, we propose a review of the different effects caused by the two different HPV virion induced pathways, and highlight the mechanisms that are responsible for causing transient subfertility and cancer.

  10. Engineering of Baculovirus Vectors for the Manufacture of Virion-Free Biopharmaceuticals

    NARCIS (Netherlands)

    Marek, M.; Oers, van M.M.; Devaraj, F.F.; Vlak, J.M.; Merten, O.W.

    2011-01-01

    A novel baculovirus-based protein expression strategy was developed to produce recombinant proteins in insect cells without contaminating baculovirus virions. This novel strategy greatly simplifies the downstream processing of biopharmaceuticals produced in insect cells. The formation of these

  11. A monoclonal antibody that neutralizes poliovirus by cross-linking virions.

    OpenAIRE

    Thomas, A A; Brioen, P; Boeyé, A

    1985-01-01

    The neutralization of type 1 poliovirus by monoclonal antibody 35-1f4 was studied. The virions were rapidly linked by antibody into oligomers and larger aggregates, followed by slow redistribution of antibody between the immune complexes. The antibody content and infectivity of immune complexes were determined. Remaining single virions were fully infectious and free of antibody. The oligomers and larger aggregates did not significantly contribute to the residual infectivity, which therefore c...

  12. A previously unidentified host protein protects retroviral DNA from autointegration

    OpenAIRE

    Lee, Myung Soo; Craigie, Robert

    1998-01-01

    Integration of a DNA copy of the viral genome into a host chromosome is an essential step in the retrovirus life cycle. The machinery that carries out the integration reaction is a nucleoprotein complex derived from the core of the infecting virion. To successfully integrate into host DNA, the viral DNA within this complex must avoid self-destructive integration into itself, a reaction termed autointegration. We have previously shown [Lee, M. S. and Craigie, R. (1994) Proc. Natl. Acad. Sci. U...

  13. Enterovirus 71 virion-associated galectin-1 facilitates viral replication and stability.

    Directory of Open Access Journals (Sweden)

    Pei-Huan Lee

    Full Text Available Enterovirus 71 (EV71 infection causes a myriad of diseases from mild hand-foot-and-mouth disease or herpangina to fatal brain stem encephalitis complicated with pulmonary edema. Several severe EV71 endemics have occurred in Asia-Pacific region, including Taiwan, and have become a serious threat to children's health. EV71 infection is initiated by the attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between viruses and cell surface receptors, soluble factors may also influence the binding of EV71 to host cells. Galectin-1 has been reported to participate in several virus infections, but is not addressed in EV71. In this study, we found that the serum levels of galectin-1 in EV71-infected children were higher than those in non-infected people. In EV71 infected cells, galectin-1 was found to be associated with the EV71 VP1 and VP3 via carbohydrate residues and subsequently released and bound to another cell surface along with the virus. EV71 propagated from galectin-1 knockdown SK-N-SH cells exhibited lower infectivity in cultured cells and less pathogenicity in mice than the virus propagated from parental cells. In addition, this galectin-1-free EV71 virus was sensitive to high temperature and lost its viability after long-term storage, which could be restored following supplement of recombinant galectin-1. Taken together, our findings uncover a new role of galectin-1 in facilitating EV71 virus infection.

  14. Cytopathogenesis of Vesicular Stomatitis virus is regulated by the PSAP motif of M protein in a species-dependent manner

    Science.gov (United States)

    Vesicular stomatitis virus (VSV) is an important vector-borne pathogen of bovine and equine species, causing a reportable vesicular disease. The matrix (M) protein of VSV is multifunctional and plays a key role in cytopathogenesis, apoptosis, host protein shut-off, and virion assembly/budding. Our ...

  15. Mixed genotype transmission bodies and virions contribute to the maintenance of diversity in an insect virus

    Science.gov (United States)

    Clavijo, Gabriel; Williams, Trevor; Muñoz, Delia; Caballero, Primitivo; López-Ferber, Miguel

    2010-01-01

    An insect nucleopolyhedrovirus naturally survives as a mixture of at least nine genotypes. Infection by multiple genotypes results in the production of virus occlusion bodies (OBs) with greater pathogenicity than those of any genotype alone. We tested the hypothesis that each OB contains a genotypically diverse population of virions. Few insects died following inoculation with an experimental two-genotype mixture at a dose of one OB per insect, but a high proportion of multiple infections were observed (50%), which differed significantly from the frequencies predicted by a non-associated transmission model in which genotypes are segregated into distinct OBs. By contrast, insects that consumed multiple OBs experienced higher mortality and infection frequencies did not differ significantly from those of the non-associated model. Inoculation with genotypically complex wild-type OBs indicated that genotypes tend to be transmitted in association, rather than as independent entities, irrespective of dose. To examine the hypothesis that virions may themselves be genotypically heterogeneous, cell culture plaques derived from individual virions were analysed to reveal that one-third of virions was of mixed genotype, irrespective of the genotypic composition of the OBs. We conclude that co-occlusion of genotypically distinct virions in each OB is an adaptive mechanism that favours the maintenance of virus diversity during insect-to-insect transmission. PMID:19939845

  16. Hepatitis C Virus-Induced Rab32 Aggregation and Its Implications for Virion Assembly

    Science.gov (United States)

    Pham, Tu M.; Tran, Si C.; Lim, Yun-Sook

    2016-01-01

    ABSTRACT Hepatitis C virus (HCV) is highly dependent on cellular factors for viral propagation. Using high-throughput next-generation sequencing, we analyzed the host transcriptomic changes and identified 30 candidate genes which were upregulated in cell culture-grown HCV (HCVcc)-infected cells. Of these candidates, we selected Rab32 for further investigation. Rab32 is a small GTPase that regulates a variety of intracellular membrane-trafficking events in various cell types. In this study, we demonstrated that both mRNA and protein levels of Rab32 were increased in HCV-infected cells. Furthermore, we showed that HCV infection converted the predominantly expressed GTP-bound Rab32 to GDP-bound Rab32, contributing to the aggregation of Rab32 and thus making it less sensitive to cellular degradation machinery. In addition, GDP-bound Rab32 selectively interacted with HCV core protein and deposited core protein into the endoplasmic reticulum (ER)-associated Rab32-derived aggregated structures in the perinuclear region, which were likely to be viral assembly sites. Using RNA interference technology, we demonstrated that Rab32 was required for the assembly step but not for other stages of the HCV life cycle. Taken together, these data suggest that HCV may modulate Rab32 activity to facilitate virion assembly. IMPORTANCE Rab32, a member of the Ras superfamily of small GTPases, regulates various intracellular membrane-trafficking events in many cell types. In this study, we showed that HCV infection concomitantly increased Rab32 expression at the transcriptional level and altered the balance between GDP- and GTP-bound Rab32 toward production of Rab32-GDP. GDP-bound Rab32 selectively interacted with HCV core protein and enriched core in the ER-associated Rab32-derived aggregated structures that were probably necessary for viral assembly. Indeed, we showed that Rab32 was specifically required for the assembly of HCV. Collectively, our study identifies that Rab32 is a novel

  17. Concepts of papillomavirus entry into host cells.

    Science.gov (United States)

    Day, Patricia M; Schelhaas, Mario

    2014-02-01

    Papillomaviruses enter basal cells of stratified epithelia. Assembly of new virions occurs in infected cells during terminal differentiation. This unique biology is reflected in the mechanism of entry. Extracellularly, the interaction of nonenveloped capsids with several host cell proteins, after binding, results in discrete conformational changes. Asynchronous internalization occurs over several hours by an endocytic mechanism related to, but distinct from macropinocytosis. Intracellular trafficking leads virions through the endosomal system, and from late endosomes to the trans-Golgi-network, before nuclear delivery. Here, we discuss the existing data with the aim to synthesize an integrated model of the stepwise process of entry, thereby highlighting key open questions. Additionally, we relate data from experiments with cultured cells to in vivo results. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Comparison of the Cowpox Virus and Vaccinia Virus Mature Virion Proteome: Analysis of the Species- and Strain-Specific Proteome.

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    Joerg Doellinger

    Full Text Available Cowpox virus (CPXV causes most zoonotic orthopoxvirus (OPV infections in Europe and Northern as well as Central Asia. The virus has the broadest host range of OPV and is transmitted to humans from rodents and other wild or domestic animals. Increasing numbers of human CPXV infections in a population with declining immunity have raised concerns about the virus' zoonotic potential. While there have been reports on the proteome of other human-pathogenic OPV, namely vaccinia virus (VACV and monkeypox virus (MPXV, the protein composition of the CPXV mature virion (MV is unknown. This study focused on the comparative analysis of the VACV and CPXV MV proteome by label-free single-run proteomics using nano liquid chromatography and high-resolution tandem mass spectrometry (nLC-MS/MS. The presented data reveal that the common VACV and CPXV MV proteome contains most of the known conserved and essential OPV proteins and is associated with cellular proteins known to be essential for viral replication. While the species-specific proteome could be linked mainly to less genetically-conserved gene products, the strain-specific protein abundance was found to be of high variance in proteins associated with entry, host-virus interaction and protein processing.

  19. Concanavalin A-mediated cell agglutinability induced by Vaccinia virions. [Uv radiation, /sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Mbuy, G.; Bubel, H.C.

    1978-12-01

    The induction of enhanced concanavalin A (Con A)-mediated cellular agglutinability by purified vaccinia virus was examined quantitatively. Increased HEp-2 cell agglutinability by the lectin occurred within the first hour of infection and persisted without further change throughout the virus infectious cycle. Ultraviolet, but not heat-inactivated, virus was as effective as infectious virus in causing increased Con A agglutinability. Inhibition of viral and host cell protein synthesis by Streptovitacin A failed to alter the lectin response to vaccinia virus infection. Fluorescein-labeled Con A was observed to form clusters and large fluorescent patches on the infected cell surface during the earliest stage of infection. Studies with /sup 125/I-labeled Con A revealed an early but minimal increase in lectin binding to infected cells. After the first hour of infection, no further increase in Con A binding was observed. When cells were exposed to purified vaccinia virus surface tubules increased Con A agglutinability comparable to that obtained with native virus was demonstrated. Con A-mediated agglutinability of cells was temperature-dependent and displayed a higher temperature transition in infected cells. These data suggest that upon contact with the host cell, vaccinia virions or surface tubules induce alterations in the plasma membrane which are reflected in an enhanced agglutinability by Con A.

  20. Interactions Between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly

    DEFF Research Database (Denmark)

    Dilley, Kari A; Nikolaitchik, Olga A; Galli, Andrea

    2017-01-01

    in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle......Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable...... into each nascent virion. These studies shed light on the mechanism by which HIV-1 achieves efficient genome packaging during virus assembly.IMPORTANCE Retrovirus assembly is a well-choreographed event, during which many viral and cellular components come together to generate infectious virions. The viral...

  1. Interactions Between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly

    DEFF Research Database (Denmark)

    Dilley, Kari A; Nikolaitchik, Olga A; Galli, Andrea

    2017-01-01

    Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable...... in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle...... into each nascent virion. These studies shed light on the mechanism by which HIV-1 achieves efficient genome packaging during virus assembly.IMPORTANCE Retrovirus assembly is a well-choreographed event, during which many viral and cellular components come together to generate infectious virions. The viral...

  2. Temperature range extension of an organically crosslinked polymer system and its successful field application for water and gas shutoff

    Energy Technology Data Exchange (ETDEWEB)

    Vasquez, Julio; Eoff, Larry; Dalrymple, Dwyann [Halliburton, Rio de Janeiro. RJ (Brazil)

    2008-07-01

    Excessive water production from hydrocarbon reservoirs is one of the most serious problems in the oil industry. Water production greatly affects the economic life of producing wells and brings along secondary problems such as sand production, corrosion, and tubular scale. Remediation techniques for controlling water production, generally referred to as conformance control, include the use of polymer systems to reduce or plug permeability to water. This paper presents the laboratory evaluation of an organically crosslinked polymer (OCP) system used as a sealant for water control problems in hydrocarbon wells. Originally, the OCP system had a limited working temperature range (140 deg to 260 deg F). Recently, an alternative base polymer (for low temperatures) and a retarder (for high temperatures) have been introduced to expand the temperature range of applicability of the OCP system from 70 deg F to 350 deg F without compromising its effectiveness or thermal stability. More than 400 jobs have been performed with the OCP system around the world to address conformance problems such as water coning/cresting, high-permeability streaks, gravel pack isolation, fracture shutoff, and casing leak repairs. This paper presents an overview of case histories that used the OCP system in various regions of the world for a wide variety of applications. (author)

  3. Swine adipose stromal cells loaded with recombinant bovine herpesvirus 4 virions expressing a foreign antigen induce potent humoral immune responses in pigs.

    Science.gov (United States)

    Donofrio, Gaetano; Taddei, Simone; Franceschi, Valentina; Capocefalo, Antonio; Cavirani, Sandro; Martinelli, Nicola; Ottonello, Simone; Ferrari, Maura

    2011-01-29

    Increasingly effective vaccination strategies are needed to counteract the high incidence of contagious diseases associated with intensive swine breeding. Recombinant viral vaccines are a promising new avenue in this direction. Key features of viral vectors suitable for immunoprophylaxis are safety, ease of manipulation and the ability to replicate in a variety of hosts. Most of the above requirements are met by bovine herpesvirus 4 (BoHV-4), a non-pathogenic dsDNA virus capable of infecting a broad range of cell types in vitro. Here we report the results of an exploratory study using an engineered BoHV-4 virus (eBoHV-4) expressing two unrelated glycoprotein antigens from bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BoHV-1), to assess the potential of recombinant BoHV-4 as a self-adjuvanted immunogen in pigs. Free eBoHV-4 virions and virions preloaded into homologous swine adipose-derived stromal cells (SADSC) were tested. Neither virus formulation elicited neutralizing anti-BoHV-4 antibodies, nor any disease symptom, yet both induced specific immune responses against the heterologous antigens. However, a much earlier (18 vs 28 days post-infection) and more robust neutralizing response against BVDV and BoHV-1 viruses was elicited by eBoHV-4-preinfected SADSCs compared to free virions. The data validate BoHV-4 as a safe and effective heterologous antigen carrier/producer and identify SADSCs as helpful tools for the formulation of increasingly efficacious recombinant immunogens for pig vaccination. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Physicochemical properties of the Ljungan virus prototype virion in different environments: inactivated by heat but resistant to acidic pH, detergents and non-physiological environments such as Virkon-containing solutions.

    Science.gov (United States)

    Ekström, Jens-Ola; Tolf, Conny; Edman, Kjell-A; Lindberg, A Michael

    2007-01-01

    It is of great importance to know how a virus particle is affected by environmental conditions. Physicochemical properties of the virion will affect the virus viability in different environments, viral transmission between hosts, and will also be important for safe handling of the virus. The physicochemical properties of the Ljungan virus (LV) prototype, 87-012, adapted to grow in cell culture were evaluated using both LV in crude cell extracts and purified virions. Replication of LV was completely inhibited by heat. Titers of LV were unaffected by acidic pH, reduced but not completely abolished by alkaline pH, and unaffected by exposure to the detergents Triton X-100 and SDS. Surprisingly, viable LV was still detected after incubation in the acidic, oxidising and detergent-containing environment produced by the commonly used disinfectant Virkon. In conclusion, LV is resilient to extreme pH, detergents and also to oxidising environments, but is sensitive to heat treatment.

  5. Dynamics of HIV-containing compartments in macrophages reveal sequestration of virions and transient surface connections.

    Directory of Open Access Journals (Sweden)

    Raphaël Gaudin

    Full Text Available During HIV pathogenesis, infected macrophages behave as "viral reservoirs" that accumulate and retain virions within dedicated internal Virus-Containing Compartments (VCCs. The nature of VCCs remains ill characterized and controversial. Using wild-type HIV-1 and a replication-competent HIV-1 carrying GFP internal to the Gag precursor, we analyzed the biogenesis and evolution of VCCs in primary human macrophages. VCCs appear roughly 14 hours after viral protein synthesis is detected, initially contain few motile viral particles, and then mature to fill up with virions that become packed and immobile. The amount of intracellular Gag, the proportion of dense VCCs, and the density of viral particles in their lumen increased with time post-infection. In contrast, the secretion of virions, their infectivity and their transmission to T cells decreased overtime, suggesting that HIV-infected macrophages tend to pack and retain newly formed virions into dense compartments. A minor proportion of VCCs remains connected to the plasma membrane overtime. Surprisingly, live cell imaging combined with correlative light and electron microscopy revealed that such connections can be transient, highlighting their dynamic nature. Together, our results shed light on the late phases of the HIV-1 cycle and reveal some of its macrophage specific features.

  6. Electron cryomicroscopy reveals different F1+F2 protein States in intact parainfluenza virions.

    Science.gov (United States)

    Ludwig, Kai; Schade, Boris; Böttcher, Christoph; Korte, Thomas; Ohlwein, Nina; Baljinnyam, Bolormaa; Veit, Michael; Herrmann, Andreas

    2008-04-01

    Electron cryomicrographs of intact parainfluenza virus 5 (PIV5) virions revealed two different surface structures, namely, a continuous layer and distinct individual spikes. The structure of these spikes reconstructed from intact virions was compared with known F ectodomain structures and was found to be different from the prefusion PIV5 F0 structure but, surprisingly, very similar to the human PIV3 F postfusion structure. Hence, we conclude that the individual F1+F2 spikes in intact PIV5 virions also correspond to the postfusion state. Since the observed fusion activity of PIV5 virions has to be associated with prefusion F1+F2 proteins, they have necessarily to be localized in the continuous surface structure. The data therefore strongly suggest that the prefusion state of the F1+F2 protein requires stabilization, most probably by the association with hemagglutinin-neuraminidase. The conversion of F1+F2 proteins from the prefusion toward the postfusion state while embedded in the virus membrane is topologically difficult to comprehend on the basis of established models and demands reconsideration of our current understanding.

  7. Kinetics of proton transport into influenza virions by the viral M2 channel.

    Directory of Open Access Journals (Sweden)

    Tijana Ivanovic

    Full Text Available M2 protein of influenza A viruses is a tetrameric transmembrane proton channel, which has essential functions both early and late in the virus infectious cycle. Previous studies of proton transport by M2 have been limited to measurements outside the context of the virus particle. We have developed an in vitro fluorescence-based assay to monitor internal acidification of individual virions triggered to undergo membrane fusion. We show that rimantadine, an inhibitor of M2 proton conductance, blocks the acidification-dependent dissipation of fluorescence from a pH-sensitive virus-content probe. Fusion-pore formation usually follows internal acidification but does not require it. The rate of internal virion acidification increases with external proton concentration and saturates with a pK(m of ∼4.7. The rate of proton transport through a single, fully protonated M2 channel is approximately 100 to 400 protons per second. The saturating proton-concentration dependence and the low rate of internal virion acidification derived from authentic virions support a transporter model for the mechanism of proton transfer.

  8. Identification of two major virion protein genes of white spot syndrome virus of shrimp

    NARCIS (Netherlands)

    Hulten, van M.C.W.; Westenberg, M.; Goodall, S.D.; Vlak, J.M.

    2000-01-01

    White Spot Syndrome Virus (WSSV) is an invertebrate virus, causing considerable mortality in shrimp. Two structural proteins of WSSV were identified. WSSV virions are enveloped nucleocapsids with a bacilliform morphology with an approximate size of 275 x 120 nm, and a tail-like extension at one end.

  9. Human Ubc9 contributes to production of fully infectious human immunodeficiency virus type 1 virions.

    Science.gov (United States)

    Jaber, Tareq; Bohl, Christopher R; Lewis, Gentry L; Wood, Charles; West, John T; Weldon, Robert A

    2009-10-01

    Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold less infectious than those produced in the presence of Ubc9. The nature of this defect was assayed for dependence on Ubc9 during viral assembly, trafficking, and Env incorporation. The Gag-mediated assembly of virus particles and protease-mediated processing of Gag and Gag-Pol were unchanged in the absence of Ubc9. However, the stability of the cell-associated Env glycoprotein was decreased and Env incorporation into released virions was altered. Interestingly, overexpression of the Ubc9 trans-dominant-negative mutant C93A, which is a defective E2-SUMO-1 conjugase, suggests that this activity may not be required for interaction with Gag, virion assembly, or infectivity. This finding demonstrates that Ubc9 plays an important role in the production of infectious HIV-1 virions.

  10. Envelope protein requirements for the assembly of infectious virions of porcine reproductive and respiratory syndrome virus

    NARCIS (Netherlands)

    Wissink, E.H.J.; Kroese, M.V.; Wijk, van H.A.; Rijsewijk, F.A.M.; Meulenberg, J.J.; Rottier, P.J.M.

    2005-01-01

    Virions of porcine reproductive and respiratory syndrome virus (PRRSV) contain six membrane proteins: the major proteins GP5 and M and the minor proteins GP2a, E, GP3, and GP4. Here, we studied the envelope protein requirements for PRRSV particle formation and infectivity using full-length cDNA

  11. Identification of a novel Lymantria dispar nucleopolyhedrovirus mutant that exhibits abnormal polyhedron formation and virion occlusion

    Science.gov (United States)

    James M. Slavicek; Melissa J. Mercer; Dana Pohlman; Mary Ellen Kelly; David S. Bischoff

    1998-01-01

    In previous studies on the formation of Lymantria dispar nuclear polyhedrosis virus (LdMNPV) few polyhedra (FP) mutants, several polyhedron formation mutants (PFM) were identified that appeared to be unique. These viral mutants are being characterized to investigate the processes of polyhedron formation and virion occlusion. Ld

  12. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses

    Science.gov (United States)

    McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T.; Dennison, S. Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S. Munir; Haynes, Barton F.; Tomaras, Georgia D.

    2016-01-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  13. Pox proteomics: mass spectrometry analysis and identification of Vaccinia virion proteins

    Directory of Open Access Journals (Sweden)

    Vemulapalli Srilakshmi

    2006-03-01

    Full Text Available Abstract Background Although many vaccinia virus proteins have been identified and studied in detail, only a few studies have attempted a comprehensive survey of the protein composition of the vaccinia virion. These projects have identified the major proteins of the vaccinia virion, but little has been accomplished to identify the unknown or less abundant proteins. Obtaining a detailed knowledge of the viral proteome of vaccinia virus will be important for advancing our understanding of orthopoxvirus biology, and should facilitate the development of effective antiviral drugs and formulation of vaccines. Results In order to accomplish this task, purified vaccinia virions were fractionated into a soluble protein enriched fraction (membrane proteins and lateral bodies and an insoluble protein enriched fraction (virion cores. Each of these fractions was subjected to further fractionation by either sodium dodecyl sulfate-polyacrylamide gel electophoresis, or by reverse phase high performance liquid chromatography. The soluble and insoluble fractions were also analyzed directly with no further separation. The samples were prepared for mass spectrometry analysis by digestion with trypsin. Tryptic digests were analyzed by using either a matrix assisted laser desorption ionization time of flight tandem mass spectrometer, a quadrupole ion trap mass spectrometer, or a quadrupole-time of flight mass spectrometer (the latter two instruments were equipped with electrospray ionization sources. Proteins were identified by searching uninterpreted tandem mass spectra against a vaccinia virus protein database created by our lab and a non-redundant protein database. Conclusion Sixty three vaccinia proteins were identified in the virion particle. The total number of peptides found for each protein ranged from 1 to 62, and the sequence coverage of the proteins ranged from 8.2% to 94.9%. Interestingly, two vaccinia open reading frames were confirmed as being expressed

  14. Structure of avian orthoreovirus virion by electron cryomicroscopy and image reconstruction.

    Science.gov (United States)

    Zhang, Xing; Tang, Jinghua; Walker, Stephen B; O'Hara, David; Nibert, Max L; Duncan, Roy; Baker, Timothy S

    2005-12-05

    Among members of the genus Orthoreovirus, family Reoviridae, a group of non-enveloped viruses with genomes comprising ten segments of double-stranded RNA, only the "non-fusogenic" mammalian orthoreoviruses (MRVs) have been studied to date by electron cryomicroscopy and three-dimensional image reconstruction. In addition to MRVs, this genus comprises other species that induce syncytium formation in cultured cells, a property shared with members of the related genus Aquareovirus. To augment studies of these "fusogenic" orthoreoviruses, we used electron cryomicroscopy and image reconstruction to analyze the virions of a fusogenic avian orthoreovirus (ARV). The structure of the ARV virion, determined from data at an effective resolution of 14.6 A, showed strong similarities to that of MRVs. Of particular note, the ARV virion has its pentameric lambda-class core turret protein in a closed conformation as in MRVs, not in a more open conformation as reported for aquareovirus. Similarly, the ARV virion contains 150 copies of its monomeric sigma-class core-nodule protein as in MRVs, not 120 copies as reported for aquareovirus. On the other hand, unlike that of MRVs, the ARV virion lacks "hub-and-spokes" complexes within the solvent channels at sites of local sixfold symmetry in the incomplete T=13l outer capsid. In MRVs, these complexes are formed by C-terminal sequences in the trimeric mu-class outer-capsid protein, sequences that are genetically missing from the homologous protein of ARVs. The channel structures and C-terminal sequences of the homologous outer-capsid protein are also genetically missing from aquareoviruses. Overall, the results place ARVs between MRVs and aquareoviruses with respect to the highlighted features.

  15. Evaluation of polyacrylamide gels with accelerator ammonium salts for water shutoff in ultralow temperature reservoirs: Gelation performance and application recommendations

    Directory of Open Access Journals (Sweden)

    Hu Jia

    2016-03-01

    Full Text Available Water shutoff in ultralow temperature reservoirs has received great attention in recent years. In previous study, we reported a phenol-formaldehyde-based gel formula with ammonium salt which can provide a gelation time between 2 hrs and 2 days at 25 °C. However, systematic evaluation and field recommendations of this gel formula when encountering complex reservoirs environment are not addressed. In this paper, how and why such practical considerations as water composition, temperature, pH, weight ratio of formaldehyde to resorcinol and contaminant Fe3+ to affect the gelation performance are examined. Brookfield DV-III and scanning electron microscopy (SEM are employed respectively for viscosity measurement and microstructure analysis. SEM results further illustrate the mechanism of the effect of salinity on gelation performance. It reveals that crosslinking done by covalent bond has great advantage for gel stability under high salinity environment. The target gel formula can provide desirable gelation time below 60 °C, perfect for 15–45 °C, while it is unfeasible to use high salinity to delay gelation at 60 °C. We summarized the effect of salinity on gelation performance of different gel formulas from the present study and published literature. The summarized data can provide important guideline for gel formula design before conducting any kinds of experiments. The variation of gelation performance at different salinity may be dominated by the interaction between crosslinker-salt-polymer, not only limited to “charge-screening effect” and “ion association” proposed by several authors. We hope the analysis encouraging further investigations. Some recommendations for field application of this gel are given in the end of this paper.

  16. Probing the HIV-1 genomic RNA trafficking pathway and dimerization by genetic recombination and single virion analyses.

    Directory of Open Access Journals (Sweden)

    Michael D Moore

    2009-10-01

    Full Text Available Once transcribed, the nascent full-length RNA of HIV-1 must travel to the appropriate host cell sites to be translated or to find a partner RNA for copackaging to form newly generated viruses. In this report, we sought to delineate the location where HIV-1 RNA initiates dimerization and the influence of the RNA transport pathway used by the virus on downstream events essential to viral replication. Using a cell-fusion-dependent recombination assay, we demonstrate that the two RNAs destined for copackaging into the same virion select each other mostly within the cytoplasm. Moreover, by manipulating the RNA export element in the viral genome, we show that the export pathway taken is important for the ability of RNA molecules derived from two viruses to interact and be copackaged. These results further illustrate that at the point of dimerization the two main cellular export pathways are partially distinct. Lastly, by providing Gag in trans, we have demonstrated that Gag is able to package RNA from either export pathway, irrespective of the transport pathway used by the gag mRNA. These findings provide unique insights into the process of RNA export in general, and more specifically, of HIV-1 genomic RNA trafficking.

  17. Glycosylation and oligomeric state of envelope protein might influence HIV-1 virion capture by α4β7 integrin.

    Science.gov (United States)

    Chand, Subhash; Messina, Emily L; AlSalmi, Wadad; Ananthaswamy, Neeti; Gao, Guofen; Uritskiy, Gherman; Padilla-Sanchez, Victor; Mahalingam, Marthandan; Peachman, Kristina K; Robb, Merlin L; Rao, Mangala; Rao, Venigalla B

    2017-08-01

    The α4ß7 integrin present on host cells recognizes the V1V2 domain of the HIV-1 envelope protein. This interaction might be involved in virus transmission. Administration of α4ß7-specific antibodies inhibit acquisition of SIV in a macaque challenge model. But the molecular details of V1V2: α4ß7 interaction are unknown and its importance in HIV-1 infection remains controversial. Our biochemical and mutational analyses show that glycosylation is a key modulator of V1V2 conformation and binding to α4ß7. Partially glycosylated, but not fully glycosylated, envelope proteins are preferred substrates for α4ß7 binding. Surprisingly, monomers of the envelope protein bound strongly to α4ß7 whereas trimers bound poorly. Our results suggest that a conformationally flexible V1V2 domain allows binding of the HIV-1 virion to the α4ß7 integrin, which might impart selectivity for the poorly glycosylated HIV-1 envelope containing monomers to be more efficiently captured by α4ß7 integrin present on mucosal cells at the time of HIV-1 transmission. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. The Host RNAs in Retroviral Particles

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    Alice Telesnitsky

    2016-08-01

    Full Text Available As they assemble, retroviruses encapsidate both their genomic RNAs and several types of host RNA. Whereas limited amounts of messenger RNA (mRNA are detectable within virion populations, the predominant classes of encapsidated host RNAs do not encode proteins, but instead include endogenous retroelements and several classes of non-coding RNA (ncRNA, some of which are packaged in significant molar excess to the viral genome. Surprisingly, although the most abundant host RNAs in retroviruses are also abundant in cells, unusual forms of these RNAs are packaged preferentially, suggesting that these RNAs are recruited early in their biogenesis: before associating with their cognate protein partners, and/or from transient or rare RNA populations. These RNAs’ packaging determinants differ from the viral genome’s, and several of the abundantly packaged host ncRNAs serve cells as the scaffolds of ribonucleoprotein particles. Because virion assembly is equally efficient whether or not genomic RNA is available, yet RNA appears critical to the structural integrity of retroviral particles, it seems possible that the selectively encapsidated host ncRNAs might play roles in assembly. Indeed, some host ncRNAs appear to act during replication, as some transfer RNA (tRNA species may contribute to nuclear import of human immunodeficiency virus 1 (HIV-1 reverse transcription complexes, and other tRNA interactions with the viral Gag protein aid correct trafficking to plasma membrane assembly sites. However, despite high conservation of packaging for certain host RNAs, replication roles for most of these selectively encapsidated RNAs—if any—have remained elusive.

  19. Thermotropic nanostructured gels with complex hierarchical structure and two gelling components for water shut-off and enhance of oil recovery

    Science.gov (United States)

    Altunina, L. K.; Kuvshinov, I. V.; Kuvshinov, V. A.; Kozlov, V. V.; Stasyeva, L. A.

    2017-12-01

    This work presents the results of laboratory and field tests of thermotropic composition MEGA with two simultaneously acting gelling components, polymer and inorganic. The composition is intended for improving oil recovery and water shut-off at oilfields developed by thermal flooding, and cyclic-steam stimulated oil production wells. The composition forms an in-situ "gel-in-gel" system with improved structural-mechanical properties, using reservoir or carrier fluid heat for gelling. The gel blocks water breakthrough into producing wells and redistribute fluid flows, thus increasing the oil recovery factor.

  20. Immunoelectron microscopic evidence for Tetherin/BST2 as the physical bridge between HIV-1 virions and the plasma membrane.

    Directory of Open Access Journals (Sweden)

    Jason Hammonds

    2010-02-01

    Full Text Available Tetherin/BST2 was identified in 2008 as the cellular factor responsible for restricting HIV-1 replication at a very late stage in the lifecycle. Tetherin acts to retain virion particles on the plasma membrane after budding has been completed. Infected cells that express large amounts of tetherin display large strings of HIV virions that remain attached to the plasma membrane. Vpu is an HIV-1 accessory protein that specifically counteracts the restriction to virus release contributed by tetherin. Tetherin is an unusual Type II transmembrane protein that contains a GPI anchor at its C-terminus and is found in lipid rafts. The leading model for the mechanism of action of tetherin is that it functions as a direct physical tether bridging virions and the plasma membrane. However, evidence that tetherin functions as a physical tether has thus far been indirect. Here we demonstrate by biochemical and immunoelectron microscopic methods that endogenous tetherin is present on the viral particle and forms a bridge between virion particles and the plasma membrane. Endogenous tetherin was found on HIV particles that were released by partial proteolytic digestion. Immunoelectron microscopy performed on HIV-infected T cells demonstrated that tetherin forms an apparent physical link between virions and connects patches of virions to the plasma membrane. Linear filamentous strands that were highly enriched in tetherin bridged the space between some virions. We conclude that tetherin is the physical tether linking HIV-1 virions and the plasma membrane. The presence of filaments with which multiple molecules of tetherin interact in connecting virion particles is strongly suggested by the morphologic evidence.

  1. Virion Structure of Iflavirus Slow Bee Paralysis Virus at 2.6-Angstrom Resolution.

    Science.gov (United States)

    Kalynych, Sergei; Přidal, Antonín; Pálková, Lenka; Levdansky, Yevgen; de Miranda, Joachim R; Plevka, Pavel

    2016-08-15

    The western honeybee (Apis mellifera) is the most important commercial insect pollinator. However, bees are under pressure from habitat loss, environmental stress, and pathogens, including viruses that can cause lethal epidemics. Slow bee paralysis virus (SBPV) belongs to the Iflaviridae family of nonenveloped single-stranded RNA viruses. Here we present the structure of the SBPV virion determined from two crystal forms to resolutions of 3.4 Å and 2.6 Å. The overall structure of the virion resembles that of picornaviruses, with the three major capsid proteins VP1 to 3 organized into a pseudo-T3 icosahedral capsid. However, the SBPV capsid protein VP3 contains a C-terminal globular domain that has not been observed in other viruses from the order Picornavirales The protruding (P) domains form "crowns" on the virion surface around each 5-fold axis in one of the crystal forms. However, the P domains are shifted 36 Å toward the 3-fold axis in the other crystal form. Furthermore, the P domain contains the Ser-His-Asp triad within a surface patch of eight conserved residues that constitutes a putative catalytic or receptor-binding site. The movements of the domain might be required for efficient substrate cleavage or receptor binding during virus cell entry. In addition, capsid protein VP2 contains an RGD sequence that is exposed on the virion surface, indicating that integrins might be cellular receptors of SBPV. Pollination by honeybees is needed to sustain agricultural productivity as well as the biodiversity of wild flora. However, honeybee populations in Europe and North America have been declining since the 1950s. Honeybee viruses from the Iflaviridae family are among the major causes of honeybee colony mortality. We determined the virion structure of an Iflavirus, slow bee paralysis virus (SBPV). SBPV exhibits unique structural features not observed in other picorna-like viruses. The SBPV capsid protein VP3 has a large C-terminal domain, five of which form

  2. Structure of Hepatitis E Virion-Sized Particle Reveals an RNA-Dependent Viral Assembly Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xing, L.; Wall, J.; Li, T.-C.; Mayazaki, N.; Simon, M. N.; Moore, M.; Wang, C.-Y.; Takeda, N.; Wakita, T.; Miyamura, T.; Cheng, R. H.

    2010-10-22

    Hepatitis E virus (HEV) induces acute hepatitis in humans with a high fatality rate in pregnant women. There is a need for anti-HEV research to understand the assembly process of HEV native capsid. Here, we produced a large virion-sized and a small T=1 capsid by expressing the HEV capsid protein in insect cells with and without the N-terminal 111 residues, respectively, for comparative structural analysis. The virion-sized capsid demonstrates a T=3 icosahedral lattice and contains RNA fragment in contrast to the RNA-free T=1 capsid. However, both capsids shared common decameric organization. The in vitro assembly further demonstrated that HEV capsid protein had the intrinsic ability to form decameric intermediate. Our data suggest that RNA binding is the extrinsic factor essential for the assembly of HEV native capsids.

  3. IFITM proteins incorporated into HIV-1 virions impair viral fusion and spread.

    Science.gov (United States)

    Compton, Alex A; Bruel, Timothée; Porrot, Françoise; Mallet, Adeline; Sachse, Martin; Euvrard, Marine; Liang, Chen; Casartelli, Nicoletta; Schwartz, Olivier

    2014-12-10

    The interferon-induced transmembrane (IFITM) proteins protect cells from diverse virus infections by inhibiting virus-cell fusion. IFITM proteins also inhibit HIV-1 replication through mechanisms only partially understood. We show that when expressed in uninfected lymphocytes, IFITM proteins exert protective effects during cell-free virus infection, but this restriction can be overcome upon HIV-1 cell-to-cell spread. However, when present in virus-producing lymphocytes, IFITM proteins colocalize with viral Env and Gag proteins and incorporate into nascent HIV-1 virions to limit entry into new target cells. IFITM in viral membranes is associated with impaired virion fusion, offering additional and more potent defense against virus spread. Thus, IFITM proteins act additively in both productively infected cells and uninfected target cells to inhibit HIV-1 spread, potentially conferring these proteins with greater breadth and potency against enveloped viruses. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Impeller radial force evolution in a large double-suction centrifugal pump during startup at the shut-off condition

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Zhichao [College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083 (China); Wang, Fujun, E-mail: wangfj@cau.edu.cn [College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083 (China); Beijing Engineering Research Center of Safety and Energy Saving Technology for Water Supply Network System, China Agricultural University, Beijing 100083 (China); Yao, Zhifeng [College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083 (China); Beijing Engineering Research Center of Safety and Energy Saving Technology for Water Supply Network System, China Agricultural University, Beijing 100083 (China); Tao, Ran [College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083 (China); Xiao, Ruofu [College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083 (China); Beijing Engineering Research Center of Safety and Energy Saving Technology for Water Supply Network System, China Agricultural University, Beijing 100083 (China); Li, Huaicheng [Shanghai Liancheng (Group) Co., Ltd., Shanghai 201812 (China)

    2016-12-15

    Highlights: • Conclude the characteristics of transient radial force in the startup process for a large double-suction centrifugal pump. • The overall direction of the radial force during startup process is also confirmed. • A formula used to calculate the transient radial force during startup process is proposed. • A relationship between radial force variation and axial vortex development in blade channel during the startup process is established. The mechanism of the radial force evolution is revealed. - Abstract: Double-suction centrifugal pumps play an important role in the main feedwater systems of nuclear power plant. The impeller radial force in a centrifugal pump varies dramatically during startup at the shut-off condition. In this study, the startup process of a large double-suction centrifugal pump is investigated using CFD. During testing, the impeller speed is accelerated from zero to its rated speed in 1.0 s (marked as t{sub 0}) and is then maintained at the rated speed. The results show that the radial force increase lags behind the impeller speed increase. At 0–0.4t{sub 0}, the radial force is small (approaching zero). At 0.4–1.4t{sub 0}, the radial force increases rapidly. After 1.4t{sub 0}, the average radial force stabilizes and reaches its maximum value of 55,619 N. The observed maximum radial force value during startup is approximately nine times as high as the radial force under rated condition. During startup, the overall radial force direction is proximate to the radial line located 25° from the volute tongue along circumferential direction. A transient radial force formula is proposed to evaluate the changes in radial force during startup. The streamline distribution in impeller passages and the impeller outlet pressure profile varying over time are produced. The relationship between radial force evolution and the varying axial-to-spiral vortex structure is analyzed. The radial force change mechanism is revealed. This research

  5. The T7-Related Pseudomonas putida Phage ϕ15 Displays Virion-Associated Biofilm Degradation Properties

    OpenAIRE

    Cornelissen, Anneleen; Ceyssens, Pieter-Jan; T'Syen, Jeroen; Van Praet, Helena; Noben, Jean-Paul; Shaburova, Olga V; Krylov, Victor N; Volckaert, Guido; Lavigne, Rob

    2011-01-01

    Formation of a protected biofilm environment is recognized as one of the major causes of the increasing antibiotic resistance development and emphasizes the need to develop alternative antibacterial strategies, like phage therapy. This study investigates the in vitro degradation of single-species Pseudomonas putida biofilms, PpG1 and RD5PR2, by the novel phage phi 15, a 'T7-like virus' with a virion-associated exopolysaccharide (EPS) depolymerase. Phage phi 15 forms plaques surrounded by grow...

  6. Vaccinia virus protein F12 associates with intracellular enveloped virions through an interaction with A36.

    Science.gov (United States)

    Johnston, Sara C; Ward, Brian M

    2009-02-01

    Vaccinia virus is the prototypical member of the family Poxviridae. Three morphologically distinct forms are produced during infection: intracellular mature virions (IMV), intracellular enveloped virions (IEV), and extracellular enveloped virions (EEV). Two viral proteins, F12 and A36, are found exclusively on IEV but not on IMV and EEV. Analysis of membranes from infected cells showed that F12 was only associated with membranes and is not an integral membrane protein. A yeast two-hybrid assay revealed an interaction between amino acids 351 to 458 of F12 and amino acids 91 to 111 of A36. We generated a recombinant vaccinia virus that expresses an F12, which lacks residues 351 to 458. Characterization of this recombinant revealed a small-plaque phenotype and a subsequent defect in virus release similar to a recombinant virus that had F12L deleted. In addition, F12 lacking residues 351 to 458 was unable to associate with membranes in infected cells. These results suggest that F12 associates with IEV through an interaction with A36 and that this interaction is critical for the function of F12 during viral egress.

  7. Exocytosis of Alphaherpesvirus Virions, Light Particles, and Glycoproteins Uses Constitutive Secretory Mechanisms

    Directory of Open Access Journals (Sweden)

    Ian B. Hogue

    2016-06-01

    Full Text Available Many molecular and cell biological details of the alphaherpesvirus assembly and egress pathway remain unclear. Recently we developed a live-cell fluorescence microscopy assay of pseudorabies virus (PRV exocytosis, based on total internal reflection fluorescence (TIRF microscopy and a virus-encoded pH-sensitive fluorescent probe. Here, we use this assay to distinguish three classes of viral exocytosis in a nonpolarized cell type: (i trafficking of viral glycoproteins to the plasma membrane, (ii exocytosis of viral light particles, and (iii exocytosis of virions. We find that viral glycoproteins traffic to the cell surface in association with constitutive secretory Rab GTPases and exhibit free diffusion into the plasma membrane after exocytosis. Similarly, both virions and light particles use these same constitutive secretory mechanisms for egress from infected cells. Furthermore, we show that viral light particles are distinct from cellular exosomes. Together, these observations shed light on viral glycoprotein trafficking steps that precede virus particle assembly and reinforce the idea that virions and light particles share a biogenesis and trafficking pathway.

  8. Bioluminescent virion shells: new tools for quantitation of AAV vector dynamics in cells and live animals.

    Science.gov (United States)

    Asokan, A; Johnson, J S; Li, C; Samulski, R J

    2008-12-01

    Current technologies for visualizing infectious pathways of viruses rely on fluorescent labeling of capsid proteins by chemical conjugation or genetic manipulation. For noninvasive in vivo imaging of such agents in mammalian tissue, we engineered bioluminescent Gaussia luciferase-tagged Adeno-associated viral (gLuc/AAV) vectors. The enzyme was incorporated into recombinant AAV serotypes 1, 2 and 8 capsids by fusing to the N-terminus of the VP2 capsid subunit to yield bioluminescent virion shells. The gLuc/AAV vectors were used to quantify kinetics of cell-surface-binding by AAV2 capsids in vitro. Bioluminescent virion shells displayed an exponential decrease in luminescent signal following cellular uptake in vitro. A similar trend was observed following intramuscular injection in vivo, although the rate of decline in bioluminescent signal varied markedly between AAV serotypes. gLuc/AAV1 and gLuc/AAV8 vectors displayed rapid decrease in bioluminescent signal to background levels within 30 min, whereas the signal from gLuc/AAV2 vectors persisted for over 2 h. Bioluminescent virion shells might be particularly useful in quantifying dynamics of viral vector uptake in cells and peripheral tissues in live animals.

  9. The in situ structural characterization of the influenza A virus matrix M1 protein within a virion.

    Science.gov (United States)

    Shishkov, Alexander V; Bogacheva, Elena N; Dolgov, Alexey A; Chulichkov, Alexey L; Knyazev, Denis G; Fedorova, Natalia V; Ksenofontov, Alexander L; Kordyukova, Larisa V; Lukashina, Elena V; Mirsky, Vladimir M; Baratova, Lyudmila A

    2009-01-01

    The first attempt has been made to suggest a model of influenza A virus matrix M1 protein spatial structure and molecule orientation within a virion on the basis of tritium planigraphy data and theoretical prediction results. Limited in situ proteolysis of the intact virions with bromelain and surface plasmon resonance spectroscopy study of the M1 protein interaction with lipid coated surfaces were used for independent confirmation of the proposed model.

  10. Tritium planigraphy comparative structural study of tobacco mosaic virus and its mutant with altered host specificity.

    Science.gov (United States)

    Dobrov, Eugenie N; Badun, Gennadii A; Lukashina, Elena V; Fedorova, Nataliya V; Ksenofontov, Alexander L; Fedoseev, Vladimir M; Baratova, Ludmila A

    2003-08-01

    Spatial organization of wild-type (strain U1) tobacco mosaic virus (TMV) and of the temperature-sensitive TMV ts21-66 mutant was compared by tritium planigraphy. The ts21-66 mutant contains two substitutions in the coat protein (Ile21-->Thr and Asp66-->Gly) and, in contrast with U1, induces a hypersensitive response (formation of necroses) on the leaves of plants bearing a host resistance gene N' (for example Nicotiana sylvestris); TMV U1 induces systemic infection (mosaic) on the leaves of such plants. Tritium distribution along the coat protein (CP) polypeptide chain was determined after labelling of both isolated CP preparations and intact virions. In the case of the isolated low-order (3-4S) CP aggregates no reliable differences in tritium distribution between U1 and ts21-66 were found. But in labelling of the intact virions a significant difference between the wild-type and mutant CPs was observed: the N-terminal region of ts21-66 CP incorporated half the amount of tritium than the corresponding region of U1 CP. This means that in U1 virions the CP N-terminal segment is more exposed on the virion surface than in ts21-66 virions. The possibility of direct participation of the N-terminal tail of U1 CP subunits in the process of the N' hypersensitive response suppression is discussed.

  11. Cleavage of the HPV16 Minor Capsid Protein L2 during Virion Morphogenesis Ablates the Requirement for Cellular Furin during De Novo Infection

    Directory of Open Access Journals (Sweden)

    Linda Cruz

    2015-11-01

    Full Text Available Infections by high-risk human papillomaviruses (HPV are the causative agents for the development of cervical cancer. As with other non-enveloped viruses, HPVs are taken up by the cell through endocytosis following primary attachment to the host cell. Through studies using recombinant pseudovirus particles (PsV, many host cellular proteins have been implicated in the process. The proprotein convertase furin has been demonstrated to cleave the minor capsid protein, L2, post-attachment to host cells and is required for infectious entry by HPV16 PsV. In contrast, using biochemical inhibition by a furin inhibitor and furin-negative cells, we show that tissue-derived HPV16 native virus (NV initiates infection independent of cellular furin. We show that HPV16 L2 is cleaved during virion morphogenesis in differentiated tissue. In addition, HPV45 is also not dependent on cellular furin, but two other alpha papillomaviruses, HPV18 and HPV31, are dependent on the activity of cellular furin for infection.

  12. Fire fighting with high risk. Firemen demand an emergency shutoff option for PV systems; Loeschen mit Risiko. Die Feuerwehr fordert von der Solarbranche ein 'Not-Aus' fuer Photovoltaikanlagen

    Energy Technology Data Exchange (ETDEWEB)

    Beneking, Andreas

    2011-01-15

    It is a horror scenario for home owners with PV systems: Firemen cannot fight a fire in a burning house because free PV cables make it too risky. Emergency shutoff technologies may offer a way out. There are several technologies already commercially available but there is no legal regulation as yet, and experts are not in agreement about the optimum concepts.

  13. CD40 ligand (CD154) incorporated into HIV virions induces activation-induced cytidine deaminase (AID) expression in human B lymphocytes.

    Science.gov (United States)

    Epeldegui, Marta; Thapa, Dharma R; De la Cruz, Justin; Kitchen, Scott; Zack, Jerome A; Martínez-Maza, Otoniel

    2010-07-06

    Most AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) arises from errors in immunoglobulin heavy-chain gene (IgH) class switch recombination (CSR) or somatic hypermutation (SHM), events that occur in germinal center (GC) B cells and require the activity of activation induced cytidine deaminase (AID). Several oncogenic viruses (EBV, HCV, HPV) can induce AID gene (AID) expression, and elevated AID expression is seen in circulating lymphocytes prior to AIDS-NHL diagnosis. Here, we report that HIV produced in peripheral blood mononuclear cells (PBMC) induced AID expression in normal human B cells. Since HIV produced in PBMC contains host cell CD40 ligand (CD40L) incorporated into the viral membrane, and CD40L is known to induce AID expression in human B cells, the role of virion-associated CD40L in HIV-induced AID expression was examined. Only viruses expressing functional CD40L were seen to induce AID expression; CD40L-negative HIV did not induce AID expression. The induction of AID expression by CD40L+ HIV was abrogated by addition of blocking anti-CD40L antibody. AID protein was detected in B cells exposed to CD40L+ HIV using intracellular multicolor flow cytometry, with most AID producing B cells expressing the CD71 activation marker on their surface. Therefore, HIV virions that express CD40L induce AID expression in B cells, and this induction appears to be due to a direct interaction between CD40L on these viruses and CD40 on B cells. These findings are consistent with a role for HIV in the direct stimulation of B cells, potentially leading to the accumulation of molecular lesions that have the potential to contribute to the development of NHL.

  14. CD40 ligand (CD154 incorporated into HIV virions induces activation-induced cytidine deaminase (AID expression in human B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Marta Epeldegui

    2010-07-01

    Full Text Available Most AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL arises from errors in immunoglobulin heavy-chain gene (IgH class switch recombination (CSR or somatic hypermutation (SHM, events that occur in germinal center (GC B cells and require the activity of activation induced cytidine deaminase (AID. Several oncogenic viruses (EBV, HCV, HPV can induce AID gene (AID expression, and elevated AID expression is seen in circulating lymphocytes prior to AIDS-NHL diagnosis. Here, we report that HIV produced in peripheral blood mononuclear cells (PBMC induced AID expression in normal human B cells. Since HIV produced in PBMC contains host cell CD40 ligand (CD40L incorporated into the viral membrane, and CD40L is known to induce AID expression in human B cells, the role of virion-associated CD40L in HIV-induced AID expression was examined. Only viruses expressing functional CD40L were seen to induce AID expression; CD40L-negative HIV did not induce AID expression. The induction of AID expression by CD40L+ HIV was abrogated by addition of blocking anti-CD40L antibody. AID protein was detected in B cells exposed to CD40L+ HIV using intracellular multicolor flow cytometry, with most AID producing B cells expressing the CD71 activation marker on their surface. Therefore, HIV virions that express CD40L induce AID expression in B cells, and this induction appears to be due to a direct interaction between CD40L on these viruses and CD40 on B cells. These findings are consistent with a role for HIV in the direct stimulation of B cells, potentially leading to the accumulation of molecular lesions that have the potential to contribute to the development of NHL.

  15. Effect of the deletion of genes encoding proteins of the extracellular virion form of vaccinia virus on vaccine immunogenicity and protective effectiveness in the mouse model.

    Directory of Open Access Journals (Sweden)

    Clement A Meseda

    Full Text Available Antibodies to both infectious forms of vaccinia virus, the mature virion (MV and the enveloped virion (EV, as well as cell-mediated immune response appear to be important for protection against smallpox. EV virus particles, although more labile and less numerous than MV, are important for dissemination and spread of virus in infected hosts and thus important in virus pathogenesis. The importance of the EV A33 and B5 proteins for vaccine induced immunity and protection in a murine intranasal challenge model was evaluated by deletion of both the A33R and B5R genes in a vaccine-derived strain of vaccinia virus. Deletion of either A33R or B5R resulted in viruses with a small plaque phenotype and reduced virus yields, as reported previously, whereas deletion of both EV protein-encoding genes resulted in a virus that formed small infection foci that were detectable and quantifiable only by immunostaining and an even more dramatic decrease in total virus yield in cell culture. Deletion of B5R, either as a single gene knockout or in the double EV gene knockout virus, resulted in a loss of EV neutralizing activity, but all EV gene knockout viruses still induced a robust neutralizing activity against the vaccinia MV form of the virus. The effect of elimination of A33 and/or B5 on the protection afforded by vaccination was evaluated by intranasal challenge with a lethal dose of either vaccinia virus WR or IHD-J, a strain of vaccinia virus that produces relatively higher amounts of EV virus. The results from multiple experiments, using a range of vaccination doses and virus challenge doses, and using mortality, morbidity, and virus dissemination as endpoints, indicate that the absence of A33 and B5 have little effect on the ability of a vaccinia vaccine virus to provide protection against a lethal intranasal challenge in a mouse model.

  16. Tagging of the vaccinia virus protein F13 with mCherry causes aberrant virion morphogenesis.

    Science.gov (United States)

    Carpentier, David C J; Hollinshead, Michael S; Ewles, Helen A; Lee, Stacey-Ann; Smith, Geoffrey L

    2017-09-20

    Vaccinia virus produces two distinct infectious virions; the single-enveloped intracellular mature virus (IMV), which remains in the cell until cell lysis, and the double-enveloped extracellular enveloped virus (EEV), which mediates virus spread. The latter is derived from a triple-enveloped intracellular enveloped virus (IEV) precursor, which is transported to the cell periphery by the kinesin-1 motor complex. This transport involves the viral protein A36 as well as F12 and E2. A36 is an integral membrane protein associated with the outer virus envelope and is the only known direct link between virion and kinesin-1 complex. Yet in the absence of A36 virion egress still occurs on microtubules, albeit at reduced efficiency. In this paper double-fluorescent labelling of the capsid protein A5 and outer-envelope protein F13 was exploited to visualize IEV transport by live-cell imaging in the absence of either A36 or F12. During the generation of recombinant viruses expressing both A5-GFP and F13-mCherry a plaque size defect was identified that was particularly severe in viruses lacking A36. Electron microscopy showed that this phenotype was caused by abnormal wrapping of IMV to form IEV, and this resulted in reduced virus egress to the cell surface. The aberrant wrapping phenotype suggests that the fluorescent fusion protein interferes with an interaction of F13 with the IMV surface that is required for tight association between IMVs and wrapping membranes. The severity of this defect suggests that these viruses are imperfect tools for characterizing virus egress.

  17. Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression.

    Directory of Open Access Journals (Sweden)

    Victoria Wahl-Jensen

    2011-10-01

    Full Text Available Zaire ebolavirus (ZEBOV infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP(1,2 is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP(1,2 (VLP(VP40-GP triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLP(VP40 (particles lacking GP(1,2 caused an aberrant response. This suggests that GP(1,2 binding to macrophages plays an important role in the immediate cellular response.

  18. The brome mosaic virus 3' untranslated sequence regulates RNA replication, recombination, and virion assembly.

    Science.gov (United States)

    Rao, A L N; Cheng Kao, C

    2015-08-03

    The 3' untranslated region in each of the three genomic RNAs of Brome mosaic virus (BMV) is highly homologous and contains a sequence that folds into a tRNA-like structure (TLS). Experiments performed over the past four decades revealed that the BMV 3' TLS regulates many important steps in BMV infection. This review summarizes in vitro and in vivo studies of the roles of the BMV 3' TLS functioning as a minus-strand promoter, in RNA recombination, and to nucleate virion assembly. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Initiation and Direction of RNA Transcription by Vesicular Stomatitis Virus Virion Transcriptase

    Science.gov (United States)

    Roy, Polly; Bishop, D. H. L.

    1973-01-01

    The initiation of RNA transcription by the virion-bound RNA transcriptase of vesicular stomatitis virus has been examined. Multiple initiation sequences have been observed, two of which have been characterized (pppApCpGp... and pppGpCp...) suggestive of a transcription process which can start at different sites along the template RNA. By the use of sequential labeling techniques and exonucleases, it has been determined that there is a 5′ to 3′ direction of product RNA synthesis. PMID:4349490

  20. Exocytosis of Varicella-Zoster Virus Virions Involves a Convergence of Endosomal and Autophagy Pathways.

    Science.gov (United States)

    Buckingham, Erin M; Jarosinski, Keith W; Jackson, Wallen; Carpenter, John E; Grose, Charles

    2016-10-01

    Varicella-zoster virus (VZV) is an extremely cell-associated herpesvirus with limited egress of viral particles. The induction of autophagy in VZV-infected monolayers is easily detectable; inhibition of autophagy leads to decreased VZV glycoprotein biosynthesis and diminished viral titers. To explain how autophagic flux could exert a proviral effect on the VZV infectious cycle, we postulated that the VZV exocytosis pathway following secondary envelopment may converge with the autophagy pathway. This hypothesis depended on known similarities between VZV gE and autophagy-related (Atg) Atg9/Atg16L1 trafficking pathways. Investigations were carried out with highly purified fractions of VZV virions. When the virion fraction was tested for the presence of autophagy and endosomal proteins, microtubule-associated protein 1 light chain (MAP1LC3B) and Ras-like GTPase 11 (Rab11) were detected. By two-dimensional (2D) and 3D imaging after immunolabeling, both proteins also colocalized with VZV gE in a proportion of cytoplasmic vesicles. When purified VZV virions were enumerated after immunoelectron microscopy, gold beads were detected on viruses following incubation with antibodies to VZV gE (∼100%), Rab11 (50%), and LC3B (30%). Examination of numerous electron micrographs demonstrated that enveloped virions were housed in single-membraned vesicles; viral particles were not observed in autophagosomes. Taken together, our data suggested that some viral particles after secondary envelopment accumulated in a heterogeneous population of single-membraned vesicular compartments, which were decorated with components from both the endocytic pathway (Rab11) and the autophagy pathway (LC3B). The latter cytoplasmic viral vesicles resembled an amphisome. VZV infection leads to increased autophagic flux, while inhibition of autophagy leads to a marked reduction in virus spread. In this investigation of the proviral role of autophagy, we found evidence for an intersection of viral

  1. Thermal conversion of filamentous potato virus X into spherical particles with different properties from virions.

    Science.gov (United States)

    Nikitin, Nikolai; Ksenofontov, Alexander; Trifonova, Ekaterina; Arkhipenko, Marina; Petrova, Ekaterina; Kondakova, Olga; Kirpichnikov, Mikhail; Atabekov, Joseph; Dobrov, Evgeny; Karpova, Olga

    2016-05-01

    We developed a method for the fast transformation of virions of tobacco mosaic virus (TMV) in so-called spherical particles (SPs) of different sizes. These SPs turned out to be highly useful for the preparation of different kinds of important biotechnological products. In this communication, we report that a representative of the flexuous helical virus group-potato virus X (PVX), produces SPs as well, but these SPs differ from TMV SPs in several important aspects. PVX SPs may be useful biotechnological devices. © 2016 Federation of European Biochemical Societies.

  2. The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress.

    Science.gov (United States)

    Newcomb, William W; Fontana, Juan; Winkler, Dennis C; Cheng, Naiqian; Heymann, J Bernard; Steven, Alasdair C

    2017-06-13

    Many viruses migrate between different cellular compartments for successive stages of assembly. The HSV-1 capsid assembles in the nucleus and then transfers into the cytoplasm. First, the capsid buds through the inner nuclear membrane, becoming coated with nuclear egress complex (NEC) protein. This yields a primary enveloped virion (PEV) whose envelope fuses with the outer nuclear membrane, releasing the capsid into the cytoplasm. We investigated the associated molecular mechanisms by isolating PEVs from US3-null-infected cells and imaging them by cryo-electron microscopy and tomography. (pUS3 is a viral protein kinase in whose absence PEVs accumulate in the perinuclear space.) Unlike mature extracellular virions, PEVs have very few glycoprotein spikes. PEVs are ~20% smaller than mature virions, and the little space available between the capsid and the NEC layer suggests that most tegument proteins are acquired later in the egress pathway. Previous studies have proposed that NEC is organized as hexamers in honeycomb arrays in PEVs, but we find arrays of heptameric rings in extracts from US3-null-infected cells. In a PEV, NEC contacts the capsid predominantly via the pUL17/pUL25 complexes which are located close to the capsid vertices. Finally, the NEC layer dissociates from the capsid as it leaves the nucleus, possibly in response to pUS3-mediated phosphorylation. Overall, nuclear egress emerges as a process driven by a program of multiple weak interactions. IMPORTANCE On its maturation pathway, the newly formed HSV-1 nucleocapsid must traverse the nuclear envelope, while respecting the integrity of that barrier. Nucleocapsids (125 nm in diameter) are too large to pass through the nuclear pore complexes that conduct most nucleocytoplasmic traffic. It is now widely accepted that the process involves envelopment/de-envelopment of a key intermediate-the primary enveloped virion. In wild-type infections, PEVs are short-lived, which has impeded study. Using a mutant

  3. Target-dependent enrichment of virions determines the reduction of high-throughput sequencing in virus discovery.

    Directory of Open Access Journals (Sweden)

    Randi Holm Jensen

    Full Text Available Viral infections cause many different diseases stemming both from well-characterized viral pathogens but also from emerging viruses, and the search for novel viruses continues to be of great importance. High-throughput sequencing is an important technology for this purpose. However, viral nucleic acids often constitute a minute proportion of the total genetic material in a sample from infected tissue. Techniques to enrich viral targets in high-throughput sequencing have been reported, but the sensitivity of such methods is not well established. This study compares different library preparation techniques targeting both DNA and RNA with and without virion enrichment. By optimizing the selection of intact virus particles, both by physical and enzymatic approaches, we assessed the effectiveness of the specific enrichment of viral sequences as compared to non-enriched sample preparations by selectively looking for and counting read sequences obtained from shotgun sequencing. Using shotgun sequencing of total DNA or RNA, viral targets were detected at concentrations corresponding to the predicted level, providing a foundation for estimating the effectiveness of virion enrichment. Virion enrichment typically produced a 1000-fold increase in the proportion of DNA virus sequences. For RNA virions the gain was less pronounced with a maximum 13-fold increase. This enrichment varied between the different sample concentrations, with no clear trend. Despite that less sequencing was required to identify target sequences, it was not evident from our data that a lower detection level was achieved by virion enrichment compared to shotgun sequencing.

  4. Immunogenicity Studies of Bivalent Inactivated Virions of EV71/CVA16 Formulated with Submicron Emulsion Systems

    Directory of Open Access Journals (Sweden)

    Chih-Wei Lin

    2014-01-01

    Full Text Available We assessed two strategies for preparing candidate vaccines against hand, foot, and mouth disease (HFMD caused mainly by infections of enterovirus (EV 71 and coxsackievirus (CV A16. We firstly design and optimize the potency of adjuvant combinations of emulsion-based delivery systems, using EV71 candidate vaccine as a model. We then perform immunogenicity studies in mice of EV71/CVA16 antigen combinations formulated with PELC/CpG. A single dose of inactivated EV71 virion (0.2 μg emulsified in submicron particles was found (i to induce potent antigen-specific neutralizing antibody responses and (ii consistently to elicit broad antibody responses against EV71 neutralization epitopes. A single dose immunogenicity study of bivalent activated EV71/CVA16 virion formulated with either Alum or PELC/CpG adjuvant showed that CVA16 antigen failed to elicit CVA16 neutralizing antibody responses and did not affect EV71-specific neutralizing antibody responses. A boosting dose of emulsified EV71/CVA16 bivalent vaccine candidate was found to be necessary to achieve high seroconversion of CVA16-specific neutralizing antibody responses. The current results are important for the design and development of prophylactic vaccines against HFMD and other emerging infectious diseases.

  5. Gp120 on HIV-1 Virions Lacks O-Linked Carbohydrate.

    Directory of Open Access Journals (Sweden)

    Elizabeth Stansell

    Full Text Available As HIV-1-encoded envelope protein traverses the secretory pathway, it may be modified with N- and O-linked carbohydrate. When the gp120s of HIV-1 NL4-3, HIV-1 YU2, HIV-1 Bal, HIV-1 JRFL, and HIV-1 JRCSF were expressed as secreted proteins, the threonine at consensus position 499 was found to be O-glycosylated. For SIVmac239, the corresponding threonine was also glycosylated when gp120 was recombinantly expressed. Similarly-positioned, highly-conserved threonines in the influenza A virus H1N1 HA1 and H5N1 HA1 envelope proteins were also found to carry O-glycans when expressed as secreted proteins. In all cases, the threonines were modified predominantly with disialylated core 1 glycans, together with related core 1 and core 2 structures. Secreted HIV-1 gp140 was modified to a lesser extent with mainly monosialylated core 1 O-glycans, suggesting that the ectodomain of the gp41 transmembrane component may limit the accessibility of Thr499 to glycosyltransferases. In striking contrast to these findings, gp120 on purified virions of HIV-1 Bal and SIV CP-MAC lacked any detectable O-glycosylation of the C-terminal threonine. Our results indicate the absence of O-linked carbohydrates on Thr499 as it exists on the surface of virions and suggest caution in the interpretation of analyses of post-translational modifications that utilize recombinant forms of envelope protein.

  6. Archaeal virus with exceptional virion architecture and the largest single-stranded DNA genome

    Science.gov (United States)

    Mochizuki, Tomohiro; Krupovic, Mart; Pehau-Arnaudet, Gérard; Sako, Yoshihiko; Forterre, Patrick; Prangishvili, David

    2012-01-01

    Known viruses build their particles using a restricted number of redundant structural solutions. Here, we describe the Aeropyrum coil-shaped virus (ACV), of the hyperthermophilic archaeon Aeropyrum pernix, with a virion architecture not previously observed in the viral world. The nonenveloped, hollow, cylindrical virion is formed from a coiling fiber, which consists of two intertwining halves of a single circular nucleoprotein. The virus ACV is also exceptional for its genomic properties. It is the only virus with a single-stranded (ss) DNA genome among the known hyperthermophilic archaeal viruses. Moreover, the size of its circular genome, 24,893 nt, is double that of the largest known ssDNA genome, suggesting an efficient solution for keeping ssDNA intact at 90–95 °C, the optimal temperature range of A. pernix growth. The genome content of ACV is in line with its unique morphology and confirms that ACV is not closely related to any known virus. PMID:22826255

  7. [Differences in spatial structures of the influenza virus M1 protein in crystal, solution and virion].

    Science.gov (United States)

    Bogacheva, E N; Dolgov, A A; Chulichkov, A L; Shishkov, A V; Ksenofontov, A L; Fedorova, N V; Baratova, L A

    2012-01-01

    Spatial structure of the influenza virus A/Puerto Rico/8/34 (PR8, subtype H1N1) M1 protein in a solution and composition of the virion was studied by tritium planigraphy technique. The special algorithm for modeling of the spatial structure is used to simulate the experiment, as well as a set of algorithms predicting secondary structure and disordered regions in proteins. Tertiary structures were refined using the program Rosetta. To compare the structures in solution and in virion, also used the X-ray diffraction data for NM-domain. The main difference between protein structure in solution and crystal is observed in the contact region of N- and M-domains, which are more densely packed in the crystalline state. Locations include the maximum label is almost identical to the unstructured regions of proteins predicted by bioinformatics analysis. These areas are concentrated in the C-domain and in the loop regions between the M-, N-, and C-domains. Analytical centrifugation and dynamic laser light scattering confirm data of tritium planigraphy. Anomalous hydrodynamic size, and low structuring of the M1 protein in solution were found. The multifunctionality of protein in the cell appears to be associated with its plastic tertiary structure, which provides at the expense of unstructured regions of contact with various molecules-partners.

  8. Orsay virus utilizes ribosomal frameshifting to express a novel protein that is incorporated into virions

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Hongbing; Franz, Carl J.; Wu, Guang; Renshaw, Hilary; Zhao, Guoyan [Departments of Molecular Microbiology and Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110 (United States); Firth, Andrew E. [Department of Pathology, University of Cambridge, Cambridge CB2 1QP (United Kingdom); Wang, David, E-mail: davewang@borcim.wustl.edu [Departments of Molecular Microbiology and Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110 (United States)

    2014-02-15

    Orsay virus is the first identified virus that is capable of naturally infecting Caenorhabditis elegans. Although it is most closely related to nodaviruses, Orsay virus differs from nodaviruses in its genome organization. In particular, the Orsay virus RNA2 segment encodes a putative novel protein of unknown function, termed delta, which is absent from all known nodaviruses. Here we present evidence that Orsay virus utilizes a ribosomal frameshifting strategy to express a novel fusion protein from the viral capsid (alpha) and delta ORFs. Moreover, the fusion protein was detected in purified virus fractions, demonstrating that it is most likely incorporated into Orsay virions. Furthermore, N-terminal sequencing of both the fusion protein and the capsid protein demonstrated that these proteins must be translated from a non-canonical initiation site. While the function of the alpha–delta fusion remains cryptic, these studies provide novel insights into the fundamental properties of this new clade of viruses. - Highlights: • Orsay virus encodes a novel fusion protein by a ribosomal frameshifting mechanism. • Orsay capsid and fusion protein is translated from a non-canonical initiation site. • The fusion protein is likely incorporated into Orsay virions.

  9. Potyvirus virion structure shows conserved protein fold and RNA binding site in ssRNA viruses.

    Science.gov (United States)

    Zamora, Miguel; Méndez-López, Eduardo; Agirrezabala, Xabier; Cuesta, Rebeca; Lavín, José L; Sánchez-Pina, M Amelia; Aranda, Miguel A; Valle, Mikel

    2017-09-01

    Potyviruses constitute the second largest genus of plant viruses and cause important economic losses in a large variety of crops; however, the atomic structure of their particles remains unknown. Infective potyvirus virions are long flexuous filaments where coat protein (CP) subunits assemble in helical mode bound to a monopartite positive-sense single-stranded RNA [(+)ssRNA] genome. We present the cryo-electron microscopy (cryoEM) structure of the potyvirus watermelon mosaic virus at a resolution of 4.0 Å. The atomic model shows a conserved fold for the CPs of flexible filamentous plant viruses, including a universally conserved RNA binding pocket, which is a potential target for antiviral compounds. This conserved fold of the CP is widely distributed in eukaryotic viruses and is also shared by nucleoproteins of enveloped viruses with segmented (-)ssRNA (negative-sense ssRNA) genomes, including influenza viruses.

  10. Understanding the Process of Envelope Glycoprotein Incorporation into Virions in Simian and Feline Immunodeficiency Viruses

    Directory of Open Access Journals (Sweden)

    José L. Affranchino

    2014-01-01

    Full Text Available The lentiviral envelope glycoproteins (Env mediate virus entry by interacting with specific receptors present at the cell surface, thereby determining viral tropism and pathogenesis. Therefore, Env incorporation into the virions formed by assembly of the viral Gag polyprotein at the plasma membrane of the infected cells is a key step in the replication cycle of lentiviruses. Besides being useful models of human immunodeficiency virus (HIV infections in humans and valuable tools for developing AIDS therapies and vaccines, simian and feline immunodeficiency viruses (SIV and FIV, respectively are relevant animal retroviruses; the study of which provides important information on how lentiviral replication strategies have evolved. In this review, we discuss the molecular mechanisms underlying the incorporation of the SIV and FIV Env glycoproteins into viral particles.

  11. Electron cryotomography of measles virus reveals how matrix protein coats the ribonucleocapsid within intact virions.

    Science.gov (United States)

    Liljeroos, Lassi; Huiskonen, Juha T; Ora, Ari; Susi, Petri; Butcher, Sarah J

    2011-11-01

    Measles virus is a highly infectious, enveloped, pleomorphic virus. We combined electron cryotomography with subvolume averaging and immunosorbent electron microscopy to characterize the 3D ultrastructure of the virion. We show that the matrix protein forms helices coating the helical ribonucleocapsid rather than coating the inner leaflet of the membrane, as previously thought. The ribonucleocapsid is folded into tight bundles through matrix-matrix interactions. The implications for virus assembly are that the matrix already tightly interacts with the ribonucleocapsid in the cytoplasm, providing a structural basis for the previously observed regulation of RNA transcription by the matrix protein. Next, the matrix-covered ribonucleocapsids are transported to the plasma membrane, where the matrix interacts with the envelope glycoproteins during budding. These results are relevant to the nucleocapsid organization and budding of other paramyxoviruses, where isolated matrix has been observed to form helices.

  12. Interactions Between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly

    DEFF Research Database (Denmark)

    Dilley, Kari A; Nikolaitchik, Olga A; Galli, Andrea

    2017-01-01

    in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle...... production when Gag is expressed at levels similar to those in cells containing one provirus. However, such enhancement is diminished when Gag is overexpressed, suggesting that the effects of viral RNA can be replaced by increased Gag concentration in cells. We also showed that the specific interactions...... between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA:Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged...

  13. Localization of the Houdinisome (Ejection Proteins inside the Bacteriophage P22 Virion by Bubblegram Imaging

    Directory of Open Access Journals (Sweden)

    Weimin Wu

    2016-08-01

    Full Text Available The P22 capsid is a T=7 icosahedrally symmetric protein shell with a portal protein dodecamer at one 5-fold vertex. Extending outwards from that vertex is a short tail, and putatively extending inwards is a 15-nm-long α-helical barrel formed by the C-terminal domains of portal protein subunits. In addition to the densely packed genome, the capsid contains three “ejection proteins” (E-proteins [gp7, gp16, and gp20] destined to exit from the tightly sealed capsid during the process of DNA delivery into target cells. We estimated their copy numbers by quantitative SDS-PAGE as approximately 12 molecules per virion of gp16 and gp7 and 30 copies of gp20. To localize them, we used bubblegram imaging, an adaptation of cryo-electron microscopy in which gaseous bubbles induced in proteins by prolonged irradiation are used to map the proteins’ locations. We applied this technique to wild-type P22, a triple mutant lacking all three E-proteins, and three mutants each lacking one E-protein. We conclude that all three E-proteins are loosely clustered around the portal axis, in the region displaced radially inwards from the portal crown. The bubblegram data imply that approximately half of the α-helical barrel seen in the portal crystal structure is disordered in the mature virion, and parts of the disordered region present binding sites for E-proteins. Thus positioned, the E-proteins are strategically placed to pass down the shortened barrel and through the portal ring and the tail, as they exit from the capsid during an infection.

  14. Nuclear Factor kappa B is required for the production of infectious human herpesvirus 8 virions

    Directory of Open Access Journals (Sweden)

    Negin N Blattman

    2014-04-01

    Full Text Available Human herpesvirus 8 (HHV8 infection leads to potent activation of nuclear factor kappa B (NFB in primary and transformed cells. We used recombinant HHV8 (rKSHV.219 expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2 and red fluorescent protein under an early HHV8 lytic gene promoter T1.1, to monitor replication during infection of human foreskin fibroblasts (HF, noting changes in NFB activity. In primary HF, NFB levels do not affect HHV8 ability to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry was able to partially overcome the deficiency induced by NFB inhibitors. Our data indicate that in primary cells, NFB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.

  15. DNA driven self-assembly of micron-sized rods using DNA-grafted bacteriophage fd virions.

    Science.gov (United States)

    Unwin, R R; Cabanas, R A; Yanagishima, T; Blower, T R; Takahashi, H; Salmond, G P C; Edwardson, J M; Fraden, S; Eiser, E

    2015-03-28

    We have functionalized the sides of fd bacteriophage virions with oligonucleotides to induce DNA hybridization driven self-assembly of high aspect ratio filamentous particles. Potential impacts of this new structure range from an entirely new building block in DNA origami structures, inclusion of virions in DNA nanostructures and nanomachines, to a new means of adding thermotropic control to lyotropic liquid crystal systems. A protocol for producing the virions in bulk is reviewed. Thiolated oligonucleotides are attached to the viral capsid using a heterobifunctional chemical linker. A commonly used system is utilized, where a sticky, single-stranded DNA strand is connected to an inert double-stranded spacer to increase inter-particle connectivity. Solutions of fd virions carrying complementary strands are mixed, annealed, and their aggregation is studied using dynamic light scattering (DLS), fluorescence microscopy, and atomic force microscopy (AFM). Aggregation is clearly observed on cooling, with some degree of local order, and is reversible when temperature is cycled through the DNA hybridization transition.

  16. Aqueous extracts from peppermint, sage and lemon balm leaves display potent anti-HIV-1 activity by increasing the virion density

    Directory of Open Access Journals (Sweden)

    Baumann Ingo

    2008-03-01

    Full Text Available Abstract Background Aqueous extracts from leaves of well known species of the Lamiaceae family were examined for their potency to inhibit infection by human immunodeficiency virus type 1 (HIV-1. Results Extracts from lemon balm (Melissa officinalis L., peppermint (Mentha × piperita L., and sage (Salvia officinalis L. exhibited a high and concentration-dependent activity against the infection of HIV-1 in T-cell lines, primary macrophages, and in ex vivo tonsil histocultures with 50% inhibitory concentrations as low as 0.004%. The aqueous Lamiaceae extracts did not or only at very high concentrations interfere with cell viability. Mechanistically, extract exposure of free virions potently and rapidly inhibited infection, while exposure of surface-bound virions or target cells alone had virtually no antiviral effect. In line with this observation, a virion-fusion assay demonstrated that HIV-1 entry was drastically impaired following treatment of particles with Lamiaceae extracts, and the magnitude of this effect at the early stage of infection correlated with the inhibitory potency on HIV-1 replication. Extracts were active against virions carrying diverse envelopes (X4 and R5 HIV-1, vesicular stomatitis virus, ecotropic murine leukemia virus, but not against a non-enveloped adenovirus. Following exposure to Lamiaceae extracts, the stability of virions as well as virion-associated levels of envelope glycoprotein and processed Gag protein were unaffected, while, surprisingly, sucrose-density equilibrium gradient analyses disclosed a marked increase of virion density. Conclusion Aqueous extracts from Lamiaceae can drastically and rapidly reduce the infectivity of HIV-1 virions at non-cytotoxic concentrations. An extract-induced enhancement of the virion's density prior to its surface engagement appears to be the most likely mode of action. By harbouring also a strong activity against herpes simplex virus type 2, these extracts may provide a basis

  17. A genetic system for Citrus Tristeza Virus using the non-natural host Nicotiana benthamiana: an update.

    Science.gov (United States)

    Ambrós, Silvia; Ruiz-Ruiz, Susana; Peña, Leandro; Moreno, Pedro

    2013-01-01

    In nature Citrus tristeza virus (CTV), genus Closterovirus, infects only the phloem cells of species of Citrus and related genera. Finding that the CTV T36 strain replicated in Nicotiana benthamiana (NB) protoplasts and produced normal virions allowed development of the first genetic system based on protoplast transfection with RNA transcribed from a full-genome cDNA clone, a laborious and uncertain system requiring several months for each experiment. We developed a more efficient system based on agroinfiltration of NB leaves with CTV-T36-based binary plasmids, which caused systemic infection in this non-natural host within a few weeks yielding in the upper leaves enough CTV virions to readily infect citrus by slash inoculation. Stem agroinoculation of citrus and NB plants with oncogenic strains of Agrobacterium tumefaciens carrying a CTV-T36 binary vector with a GUS marker, induced GUS positive galls in both species. However, while most NB tumors were CTV positive and many plants became systemically infected, no coat protein or viral RNA was detected in citrus tumors, even though CTV cDNA was readily detected by PCR in the same galls. This finding suggests (1) strong silencing or CTV RNA processing in transformed cells impairing infection progress, and (2) the need for using NB as an intermediate host in the genetic system. To maintain CTV-T36 in NB or assay other CTV genotypes in this host, we also tried to graft-transmit the virus from infected to healthy NB, or to mechanically inoculate NB leaves with virion extracts. While these trials were mostly unsuccessful on non-treated NB plants, agroinfiltration with silencing suppressors enabled for the first time infecting NB plants by side-grafting and by mechanical inoculation with virions, indicating that previous failure to infect NB was likely due to virus silencing in early infection steps. Using NB as a CTV host provides new possibilities to study virus-host interactions with a simple and reliable system.

  18. Nucleotide sequence of the 5'nontranslated and virion polypeptides regions of coxsackievirus B6.

    Science.gov (United States)

    Kato, S; Tsutsumi, R; Sato, S

    1999-01-01

    The nucleotide sequence of coxsackievirus B6 (CVB6) has been determined, and the nucleotides encoding the 5' nontranslated region (5' NTR) and virion polypeptides (VP4, 2, 3 and 1) were compared with other serotype CVBs. An Unweighted Pair-Group Method Analysis (UPGMA) of phylogenetic trees indicated that the 5' NTR of CVB6 locates on an independent branch from the other CVBs. The tree based on the amino acid sequences showed that CVB6 has close correlation with CVB4 in the VP4 and VP2 regions, with CVB1 and CVB5 in the VP3 region, and with CVB5 in the VP1 region. Amino acid sequences of variable regions within the VP2, VP3, and VP1 of CVB6 were unique among CVBs. Thus, by comparison of the nucleotide and amino acid sequences of these variable regions, CVB6 can be easily distinguished from other serotypes. In addition, serine, instead of glycine, was found to locate at the amino-terminus of the VP1 region of CVB6, indicating that CVB6 has a unique cleavage site (i.e., glutamine/serine instead of glutamine/glycine) for proteinase 3C of Picornaviridae.

  19. Oligomerization within Virions and Subcellular Localization of Human Immunodeficiency Virus Type 1 Integrase

    Science.gov (United States)

    Petit, Caroline; Schwartz, Olivier; Mammano, Fabrizio

    1999-01-01

    Previous biochemical and genetic evidence indicated that the functional form of retroviral integrase protein (IN) is a multimer. A direct demonstration of IN oligomerization during the infectious cycle was, however, missing, due to the absence of a sensitive detection method. We describe here the generation of infectious human immunodeficiency virus type 1 (HIV-1) viral clones carrying IN protein tagged with highly antigenic epitopes. In this setting, we could readily visualize IN both in producer cells and in viral particles. More interestingly, we detected IN oligomers, the formation of which was dependent on disulfide bridges and took place inside virions. Additionally, expression of a tagged HIV-1 IN in the absence of other viral components resulted in almost exclusive nuclear accumulation of the protein. Mutation of a conserved cysteine in the proposed dimer interface determined the loss of viral infectivity, associated with a reduction of IN oligomer formation and the redistribution of the mutated protein in the nucleus and cytoplasm. Epitope tagging of HIV-1 IN expressed alone or in the context of a replication-competent viral clone provides powerful tools to validate debated issues on the implication of this enzyme in different steps of the viral cycle. PMID:10233971

  20. Virion polypeptide heterogeneity among virulent and avirulent strains of eastern equine encephalitis (EEE) virus.

    Science.gov (United States)

    Walder, R; Rosato, R R; Eddy, G A

    1981-01-01

    Comparative analysis of structural virion polypeptides of 24 selected EEE virus strains, representing North and South American types, was performed by one-dimensional discontinuous sodium dodecyl sulfate (SDS)-polyacrylamide-gel electrophoresis (PAGE). The structural proteins of different EEE virus isolates, resolved by this method, exhibited mol.wts. values in the range of 57-60 X 10(3) for (E-1), 51-54 X 10(3) for (E-2) and 35-38 X 10(3) daltons for the core (NP) nucleocapsid. The exception was the South American human lethal virus, TRVL-89287 strain, which was shown to possess only a single envelope glycoprotein. The high molecular weight envelope (E-1) glycoprotein species was absent or co-migrated adjacent to the smaller envelope (E-2) glycoprotein. Results indicated similarities in the core (NP) proteins, however greater variability in the envelope (E-/ and/or E-2) glycoproteins. Based on these variations seven distinct profiles could be observed among the EEE virus strain studied. The classification based on the patterns of structural polypeptides obtained by SDS-PAGE of these strains does not correlate well with any other previously reported in vitro characteristics (antigenic subtypes, HTP elution profiles) nor with the in vivo virulence markers.

  1. Hemozoin as a novel adjuvant for inactivated whole virion influenza vaccine.

    Science.gov (United States)

    Uraki, Ryuta; Das, Subash C; Hatta, Masato; Kiso, Maki; Iwatsuki-Horimoto, Kiyoko; Ozawa, Makoto; Coban, Cevayir; Ishii, Ken J; Kawaoka, Yoshihiro

    2014-09-15

    Because vaccination is an effective means to protect humans from influenza viruses, extensive efforts have been made to develop not only new vaccines, but also for new adjuvants to enhance the efficacy of existing inactivated vaccines. Here, we examined the adjuvanticity of synthetic hemozoin, a synthetic version of the malarial by-product hemozoin, on the vaccine efficacy of inactivated whole influenza viruses in a mouse model. We found that mice immunized twice with hemozoin-adjuvanted inactivated A/California/04/2009 (H1N1pdm09) or A/Vietnam/1203/2004 (H5N1) virus elicited higher virus-specific antibody responses than did mice immunized with non-adjuvanted counterparts. Furthermore, mice immunized with hemozoin-adjuvanted inactivated viruses were better protected from lethal challenge with influenza viruses than were mice immunized with non-adjuvanted inactivated vaccines. Our results show that hemozoin improves the immunogenicity of inactivated influenza viruses, and is thus a promising adjuvant for inactivated whole virion influenza vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Visualization of herpes simplex virus type 1 virions using fluorescent colors.

    Science.gov (United States)

    Etienne, Lyns; Joshi, Poorval; Dingle, Laura; Huang, Eugene; Grzesik, Peter; Desai, Prashant J

    2017-03-01

    Our laboratory was one of the first to engineer a live fluorescent tag, enhanced green fluorescent protein (eGFP), that marked the capsid of herpes simplex virus type 1 (HSV-1) and subsequently maturing virus as the particle made its way to the cell surface. In the present study we sought to increase the repertoire of colors available as fusion to the small capsid protein, VP26, so that they can be used alone or in conjunction with other fluorescent tags (fused to other HSV proteins) to follow the virus as it enters and replicates within the cell. We have now generated viruses expressing VP26 fusions with Cerulean, Venus, mOrange, tdTomato, mCherry, and Dronpa3 fluorescent proteins. These fusions were made in a repaired UL35 gene (VP26) background. These fusions do not affect the replication properties of the virus expressing the fusion polypeptide and the fusion tag was stably associated with intranuclear capsids and mature virions. Of note we could not isolate viruses expressing fusions with fluorescent proteins that have a tendency to dimerize. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. The tripartite virions of the brome mosaic virus have distinct physical properties that affect the timing of the infection process.

    Science.gov (United States)

    Vaughan, Robert; Tragesser, Brady; Ni, Peng; Ma, Xiang; Dragnea, Bogdan; Kao, C Cheng

    2014-06-01

    The three subsets of virions that comprise the Brome mosaic virus (BMV) were previously thought to be indistinguishable. This work tested the hypothesis that distinct capsid-RNA interactions in the BMV virions allow different rates of viral RNA release. Several results support distinct interactions between the capsid and the BMV genomic RNAs. First, the deletion of the first eight residues of the BMV coat protein (CP) resulted in the RNA1-containing particles having altered morphologies, while those containing RNA2 were unaffected. Second, subsets of the BMV particles separated by density gradients into a pool enriched for RNA1 (B1) and for RNA2 and RNA3/4 (B2.3/4) were found to have different physiochemical properties. Compared to the B2.3/4 particles, the B1 particles were more sensitive to protease digestion and had greater resistivity to nanoindentation by atomic force microscopy and increased susceptibility to nuclease digestion. Mapping studies showed that portions of the arginine-rich N-terminal tail of the CP could interact with RNA1. Mutational analysis in the putative RNA1-contacting residues severely reduced encapsidation of BMV RNA1 without affecting the encapsidation of RNA2. Finally, during infection of plants, the more easily released RNA1 accumulated to higher levels early in the infection. Viruses with genomes packaged in distinct virions could theoretically release the genomes at different times to regulate the timing of gene expression. Using an RNA virus composed of three particles, we demonstrated that the RNA in one of the virions is released more easily than the other two in vitro. The differential RNA release is due to distinct interactions between the viral capsid protein and the RNAs. The ease of RNA release is also correlated with the more rapid accumulation of that RNA in infected plants. Our study identified a novel role for capsid-RNA interactions in the regulation of a viral infection.

  4. Vaccinia Virus Protein F12 Associates with Intracellular Enveloped Virions through an Interaction with A36▿

    Science.gov (United States)

    Johnston, Sara C.; Ward, Brian M.

    2009-01-01

    Vaccinia virus is the prototypical member of the family Poxviridae. Three morphologically distinct forms are produced during infection: intracellular mature virions (IMV), intracellular enveloped virions (IEV), and extracellular enveloped virions (EEV). Two viral proteins, F12 and A36, are found exclusively on IEV but not on IMV and EEV. Analysis of membranes from infected cells showed that F12 was only associated with membranes and is not an integral membrane protein. A yeast two-hybrid assay revealed an interaction between amino acids 351 to 458 of F12 and amino acids 91 to 111 of A36. We generated a recombinant vaccinia virus that expresses an F12, which lacks residues 351 to 458. Characterization of this recombinant revealed a small-plaque phenotype and a subsequent defect in virus release similar to a recombinant virus that had F12L deleted. In addition, F12 lacking residues 351 to 458 was unable to associate with membranes in infected cells. These results suggest that F12 associates with IEV through an interaction with A36 and that this interaction is critical for the function of F12 during viral egress. PMID:19052096

  5. BST2/CD317 counteracts human coronavirus 229E productive infection by tethering virions at the cell surface

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shiu-Mei [Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, Taipei 11217, Taiwan (China); Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Huang, Kuo-Jung [Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, Taipei 11217, Taiwan (China); Wang, Chin-Tien, E-mail: chintien@ym.edu.tw [Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, Taipei 11217, Taiwan (China); Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)

    2014-01-20

    Bone marrow stromal antigen 2 (BST2), an interferon-inducible antiviral factor, has been shown to block the release of various enveloped viruses from cells. It has also been identified as an innate immune system component. Most enveloped viruses subject to BST2 restriction bud at the plasma membrane. Here we report our findings that (a) the production of human coronavirus 229E (HCoV-229E) progeny viruses, whose budding occurs at the ER-Golgi intermediate compartment (ERGIC), markedly decreases in the presence of BST2; and (b) BST2 knockdown expression results in enhanced HCoV-229E virion production. Electron microscopy analyses indicate that HCoV-229E virions are tethered to cell surfaces or intracellular membranes by BST2. Our results suggest that BST2 exerts a broad blocking effect against enveloped virus release, regardless of whether budding occurs at the plasma membrane or intracellular compartments. - Highlights: • BST2 knockdown expression results in enhanced HCoV-229E egress. • HCoV-229E virions are tethered to cell surfaces or intracellular membranes by BST2. • HCoV-229E infection at high MOI can significantly downregulate HeLa BST2 and rescue HIV-1 egress.

  6. Determination of avian influenza A (H9N2) virions by inductively coupled plasma mass spectrometry based magnetic immunoassay with gold nanoparticles labeling

    Science.gov (United States)

    Xiao, Guangyang; Chen, Beibei; He, Man; Shi, Kaiwen; Zhang, Xing; Li, Xiaoting; Wu, Qiumei; Pang, Daiwen; Hu, Bin

    2017-12-01

    Avian influenza viruses are the pathogens of global poultry epidemics, and may even cause the human infections. Here, we proposed a novel inductively coupled plasma mass spectrometry (ICP-MS) based immunoassay with gold nanoparticles (Au NPs) labeling for the determination of H9N2 virions. Magnetic-beads modified with anti-influenza A H9N2 hemagglutinin mono-antibody (mAb-HA) were utilized for the capture of H9N2 virions in complex matrix; and Au NPs conjugated with mAb-HA were employed for the specific labeling of H9N2 virions for subsequent ICP-MS detection. With a sandwich immunoassay strategy, this method exhibited a high specificity for H9N2 among other influenza A virions such as H1N1 and H3N2. Under the optimized conditions, this method could detect as low as 0.63 ng mL- 1 H9N2 virions with the linear range of 2-400 ng mL- 1, the relative standard deviation for seven replicate detections of H9N2 virions was 7.2% (c = 10 ng mL- 1). The developed method was applied for the detection of H9N2 virions in real-world chicken dung samples, and the recovery for the spiking samples was 91.4-116.9%. This method is simple, rapid, sensitive, selective, reliable and has a good application potential for virions detection in real-world samples.

  7. The Envelope Gene of Hepatitis B Virus Is Implicated in Both Differential Virion Secretion and Genome Replication Capacities between Genotype B and Genotype C Isolates.

    Science.gov (United States)

    Jia, Haodi; Qin, Yanli; Chen, Chaoyang; Zhang, Fei; Li, Cheng; Zong, Li; Wang, Yongxiang; Zhang, Jiming; Li, Jisu; Wen, Yumei; Tong, Shuping

    2017-03-28

    Chronic infection by hepatitis B virus (HBV) genotype C is associated with a prolonged replicative phase and an increased risk of liver cancer, compared with genotype B infection. We previously found lower replication capacity but more efficient virion secretion by genotype C than genotype B isolates. Virion secretion requires interaction between core particles and ENVELOPE proteins. In the present study, chimeric constructs between genotype B and genotype C clones were generated to identify the structural basis for differential virion secretion. In addition to dimeric constructs, we also employed 1.1mer constructs, where the cytomegalovirus (CMV) promoter drove pregenomic RNA transcription. Through transient transfection experiments in Huh7 cells, we found that exchanging the entire envelope gene or just its S region could enhance virion secretion by genotype B clones while diminishing virion secretion by genotype C. Site-directed mutagenesis established the contribution of genotype-specific divergence at codons 108 and 115 in the preS1 region, as well as codon 126 in the S region, to differential virion secretion. Surprisingly, exchanging the envelope gene or just its S region, but not the core gene or 3' S region, could markedly increase intracellular replicative DNA for genotype C clones but diminish that for genotype B, although the underlying mechanism remains to be clarified.

  8. The T7-related Pseudomonas putida phage φ15 displays virion-associated biofilm degradation properties.

    Directory of Open Access Journals (Sweden)

    Anneleen Cornelissen

    Full Text Available Formation of a protected biofilm environment is recognized as one of the major causes of the increasing antibiotic resistance development and emphasizes the need to develop alternative antibacterial strategies, like phage therapy. This study investigates the in vitro degradation of single-species Pseudomonas putida biofilms, PpG1 and RD5PR2, by the novel phage ϕ15, a 'T7-like virus' with a virion-associated exopolysaccharide (EPS depolymerase. Phage ϕ15 forms plaques surrounded by growing opaque halo zones, indicative for EPS degradation, on seven out of 53 P. putida strains. The absence of haloes on infection resistant strains suggests that the EPS probably act as a primary bacterial receptor for phage infection. Independent of bacterial strain or biofilm age, a time and dose dependent response of ϕ15-mediated biofilm degradation was observed with generally a maximum biofilm degradation 8 h after addition of the higher phage doses (10(4 and 10(6 pfu and resistance development after 24 h. Biofilm age, an in vivo very variable parameter, reduced markedly phage-mediated degradation of PpG1 biofilms, while degradation of RD5PR2 biofilms and ϕ15 amplification were unaffected. Killing of the planktonic culture occurred in parallel with but was always more pronounced than biofilm degradation, accentuating the need for evaluating phages for therapeutic purposes in biofilm conditions. EPS degrading activity of recombinantly expressed viral tail spike was confirmed by capsule staining. These data suggests that the addition of high initial titers of specifically selected phages with a proper EPS depolymerase are crucial criteria in the development of phage therapy.

  9. Regulation of the Host Antiviral State by Intercellular Communications

    Directory of Open Access Journals (Sweden)

    Sonia Assil

    2015-08-01

    Full Text Available Viruses usually induce a profound remodeling of host cells, including the usurpation of host machinery to support their replication and production of virions to invade new cells. Nonetheless, recognition of viruses by the host often triggers innate immune signaling, preventing viral spread and modulating the function of immune cells. It conventionally occurs through production of antiviral factors and cytokines by infected cells. Virtually all viruses have evolved mechanisms to blunt such responses. Importantly, it is becoming increasingly recognized that infected cells also transmit signals to regulate innate immunity in uninfected neighboring cells. These alternative pathways are notably mediated by vesicular secretion of various virus- and host-derived products (miRNAs, RNAs, and proteins and non-infectious viral particles. In this review, we focus on these newly-described modes of cell-to-cell communications and their impact on neighboring cell functions. The reception of these signals can have anti- and pro-viral impacts, as well as more complex effects in the host such as oncogenesis and inflammation. Therefore, these “broadcasting” functions, which might be tuned by an arms race involving selective evolution driven by either the host or the virus, constitute novel and original regulations of viral infection, either highly localized or systemic.

  10. Widespread disruption of host transcription termination in HSV-1 infection

    Science.gov (United States)

    Rutkowski, Andrzej J.; Erhard, Florian; L'Hernault, Anne; Bonfert, Thomas; Schilhabel, Markus; Crump, Colin; Rosenstiel, Philip; Efstathiou, Stacey; Zimmer, Ralf; Friedel, Caroline C.; Dölken, Lars

    2015-01-01

    Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for virus-induced host shut-off. Here we show that global changes in transcription and RNA processing and their impact on translation can be analysed in a single experimental setting by applying 4sU-tagging of newly transcribed RNA and ribosome profiling to lytic HSV-1 infection. Unexpectedly, we find that HSV-1 triggers the disruption of transcription termination of cellular, but not viral, genes. This results in extensive transcription for tens of thousands of nucleotides beyond poly(A) sites and into downstream genes, leading to novel intergenic splicing between exons of neighbouring cellular genes. As a consequence, hundreds of cellular genes seem to be transcriptionally induced but are not translated. In contrast to previous reports, we show that HSV-1 does not inhibit co-transcriptional splicing. Our approach thus substantially advances our understanding of HSV-1 biology and establishes HSV-1 as a model system for studying transcription termination. PMID:25989971

  11. Analysis of the role of the coat protein N-terminal segment in Potato virus X virion stability and functional activity.

    Science.gov (United States)

    Lukashina, Elena; Ksenofontov, Alexander; Fedorova, Natalia; Badun, Gennady; Mukhamedzhanova, Anna; Karpova, Olga; Rodionova, Nina; Baratova, Lyudmila; Dobrov, Evgeny

    2012-01-01

    Previously, we have reported that intact Potato virus X (PVX) virions cannot be translated in cell-free systems, but acquire this capacity by the binding of PVX-specific triple gene block protein 1 (TGBp1) or after phosphorylation of the exposed N-terminal segment of intravirus coat protein (CP) by protein kinases. With the help of in vitro mutagenesis, a nonphosphorylatable PVX mutant (denoted ST PVX) was prepared in which all 12 S and T residues in the 20-residue-long N-terminal CP segment were substituted by A or G. Contrary to expectations, ST PVX was infectious, produced normal progeny and was translated in vitro in the absence of any additional factors. We suggest that the N-terminal PVX CP segment somehow participates in virion assembly in vivo and that CP subunits in ST virions may differ in structure from those in the wild-type (UK3 strain). In the present work, to test this suggestion, we performed a comparative tritium planigraphy study of CP structure in UK3 and ST virions. It was found that the profile of tritium incorporation into ST mutant virions in some CP segments differed from that of normal UK3 virions and from UK3 complexed with the PVX movement protein TGBp1. It is proposed that amino acid substitutions in ST CP and the TGBp1-driven remodelling of UK3 virions induce structural alterations in intravirus CPs. These alterations affect the predicted RNA recognition motif of PVX CP, but in different ways: for ST PVX, labelling is increased in α-helices 6 and 7, whereas, in remodelled UK3, labelling is increased in the β-sheet strands β3, β4 and β5. © 2011 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2011 BSPP AND BLACKWELL PUBLISHING LTD.

  12. Lymphotropic Virions Affect Chemokine Receptor-Mediated Neural Signaling and Apoptosis: Implications for Human Immunodeficiency Virus Type 1-Associated Dementia

    Science.gov (United States)

    Zheng, Jialin; Ghorpade, Anuja; Niemann, Douglas; Cotter, Robin L.; Thylin, Michael R.; Epstein, Leon; Swartz, Jennifer M.; Shepard, Robin B.; Liu, Xiaojuan; Nukuna, Adeline; Gendelman, Howard E.

    1999-01-01

    Chemokine receptors pivotal for human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes and macrophages (CCR3, CCR5, and CXCR4) are expressed on neural cells (microglia, astrocytes, and/or neurons). It is these cells which are damaged during progressive HIV-1 infection of the central nervous system. We theorize that viral coreceptors could effect neural cell damage during HIV-1-associated dementia (HAD) without simultaneously affecting viral replication. To these ends, we studied the ability of diverse viral strains to affect intracellular signaling and apoptosis of neurons, astrocytes, and monocyte-derived macrophages. Inhibition of cyclic AMP, activation of inositol 1,4,5-trisphosphate, and apoptosis were induced by diverse HIV-1 strains, principally in neurons. Virions from T-cell-tropic (T-tropic) strains (MN, IIIB, and Lai) produced the most significant alterations in signaling of neurons and astrocytes. The HIV-1 envelope glycoprotein, gp120, induced markedly less neural damage than purified virions. Macrophage-tropic (M-tropic) strains (ADA, JR-FL, Bal, MS-CSF, and DJV) produced the least neural damage, while 89.6, a dual-tropic HIV-1 strain, elicited intermediate neural cell damage. All T-tropic strain-mediated neuronal impairments were blocked by the CXCR4 antibody, 12G5. In contrast, the M-tropic strains were only partially blocked by 12G5. CXCR4-mediated neuronal apoptosis was confirmed in pure populations of rat cerebellar granule neurons and was blocked by HA1004, an inhibitor of calcium/calmodulin-dependent protein kinase II, protein kinase A, and protein kinase C. Taken together, these results suggest that progeny HIV-1 virions can influence neuronal signal transduction and apoptosis. This process occurs, in part, through CXCR4 and is independent of CD4 binding. T-tropic viruses that traffic in and out of the brain during progressive HIV-1 disease may play an important role in HAD neuropathogenesis. PMID:10482576

  13. Interplay between Human Cytomegalovirus and Intrinsic/Innate Host Responses: A Complex Bidirectional Relationship

    Science.gov (United States)

    Rossini, Giada; Cerboni, Cristina; Santoni, Angela; Landini, Maria Paola; Landolfo, Santo; Gatti, Deborah; Gribaudo, Giorgio; Varani, Stefania

    2012-01-01

    The interaction between human cytomegalovirus (HCMV) and its host is a complex process that begins with viral attachment and entry into host cells, culminating in the development of a specific adaptive response that clears the acute infection but fails to eradicate HCMV. We review the viral and cellular partners that mediate early host responses to HCMV with regard to the interaction between structural components of virions (viral glycoproteins) and cellular receptors (attachment/entry receptors, toll-like receptors, and other nucleic acid sensors) or intrinsic factors (PML, hDaxx, Sp100, viperin, interferon inducible protein 16), the reactions of innate immune cells (antigen presenting cells and natural killer cells), the numerous mechanisms of viral immunoevasion, and the potential exploitation of events that are associated with early phases of virus-host interplay as a therapeutic strategy. PMID:22701276

  14. Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication.

    Science.gov (United States)

    Li, Chuntian; Zhu, Zixiang; Du, Xiaoli; Cao, Weijun; Yang, Fan; Zhang, Xiangle; Feng, Huanhuan; Li, Dan; Zhang, Keshan; Liu, Xiangtao; Zheng, Haixue

    2017-09-01

    The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and activation in porcine kidney (PK-15) cells. The viral nonstructural protein 3C proteinase (3Cpro) is identified to be responsible for this inhibition. However, it is independent of the well-known proteinase activity of 3Cpro or 3Cpro-induced shutoff of host protein synthesis. We show that 3Cpro induces PKR degradation by lysosomal pathway and no interaction is determined between 3Cpro and PKR. Together, our results indicate that PKR acts an important antiviral factor during FMDV infection, and FMDV has evolved a strategy to overcome PKR-mediated antiviral role by downregulation of PKR protein. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Short distance movement of genomic negative strands in a host and nonhost for Sugarcane mosaic virus (SCMV

    Directory of Open Access Journals (Sweden)

    Hernández-Vela Juan

    2011-01-01

    Full Text Available Abstract Background In order to obtain an initial and preliminary understanding of host and nonhost resistance in the initial step of potyvirus replication, both positive and negative Sugarcane mosaic virus (SCMV strands where traced in inoculated and systemic leaves in host and nonhost resistant maize and sugarcane for one Mexican potyviral isolate (SCMV-VER1. Intermediary replication forms, such as the negative viral strand, seem to only move a short distance as surveyed by RT-PCR analysis and ELISA in different leaves. Virus purification was also done in leaves and stems. Results Susceptible maize plants allowed for viral SCMV replication, cell-to-cell, and long distance movement, as indicated by the presence of the coat protein along the plant. In the host resistant maize plants for the SCMV-VER1 isolate, the virus was able to establish the disease though the initial steps of virus replication, as detected by the presence of negative strands, in the basal area of the inoculated leaves at six and twelve days post inoculation. The nonhost sugarcane for SCMV-VER1 and the host sugarcane for SCMV-CAM6 also allowed the initial steps of viral replication for the VER1 isolate in the local inoculated leaf. SCMV-VER1 virions could be extracted from stems of susceptible maize with higher titers than leaves. Conclusion Nonhost and host resistance allow the initial steps of potyvirus SCMV replication, as shown by the negative strands' presence. Furthermore, both hosts allow the negative viral strands' local movement, but not their systemic spread through the stem. The presence of larger amounts of extractable virions from the stem (as compared to the leaves in susceptible maize lines suggests their long distance movement as assembled particles. This will be the first report suggesting the long distance movement of a monocot potyvirus as a virion.

  16. The bovine herpesvirus type 1 UL3.5 open reading frame encodes a virion structural protein.

    Science.gov (United States)

    Schikora, B; Lu, Z; Kutish, G F; Rock, D; Magyar, G; Letchworth, G J

    1998-01-05

    The bovine herpesvirus type 1 (BHV-1) open reading frame (ORF) UL3.5 is similar to ORFs found in pseudorabies virus, infectious laryngotracheitis virus, equine herpesvirus type 1, and varicella zoster virus, but clearly absent from herpes simplex virus. The published sequence for this ORF predicts a 126-amino-acid (13.2 kDa) protein product with an isoelectric point of 12.3. We confirmed the UL3.5 sequence, expressed the ORF as a glutathione-S-transferase fusion protein, and made rabbit antibodies against the purified fusion protein. The antiserum detected a 13-kDa protein in Western blots of MDBK cells infected with BHV-1, but not with other herpesviruses or uninfected cells. The BHV-1 UL3.5 protein was characterized as a component of the virion envelope or tegument because it was expressed as a late protein, it was present in the cytoplasm but not the nucleus of infected cells, and it was removed from purified virions by detergent extraction.

  17. Modeling of Virion Collisions in Cervicovaginal Mucus Reveals Limits on Agglutination as the Protective Mechanism of Secretory Immunoglobulin A.

    Science.gov (United States)

    Chen, Alex; McKinley, Scott A; Shi, Feng; Wang, Simi; Mucha, Peter J; Harit, Dimple; Forest, M Gregory; Lai, Samuel K

    2015-01-01

    Secretory immunoglobulin A (sIgA), a dimeric antibody found in high quantities in the gastrointestinal mucosa, is broadly associated with mucosal immune protection. A distinguishing feature of sIgA is its ability to crosslink pathogens, thereby creating pathogen/sIgA aggregates that are too large to traverse the dense matrix of mucin fibers in mucus layers overlying epithelial cells and consequently reducing infectivity. Here, we use modeling to investigate this mechanism of "immune exclusion" based on sIgA-mediated agglutination, in particular the potential use of sIgA to agglutinate HIV in cervicovaginal mucus (CVM) and prevent HIV transmission. Utilizing reported data on HIV diffusion in CVM and semen, we simulate HIV collision kinetics in physiologically-thick mucus layers-a necessary first step for sIgA-induced aggregation. We find that even at the median HIV load in semen of acutely infected individuals possessing high viral titers, over 99% of HIV virions will penetrate CVM and reach the vaginal epithelium without colliding with another virion. These findings imply that agglutination is unlikely to be the dominant mechanism of sIgA-mediated protection against HIV or other sexually transmitted pathogens. Rather, we surmise that agglutination is most effective against pathogens either present at exceedingly high concentrations or that possess motility mechanisms other than Brownian diffusion that significantly enhance encounter rates.

  18. Differential Expression of HERV-K (HML-2 Proviruses in Cells and Virions of the Teratocarcinoma Cell Line Tera-1

    Directory of Open Access Journals (Sweden)

    Neeru Bhardwaj

    2015-03-01

    Full Text Available Human endogenous retrovirus (HERV-K (HML-2 proviruses are among the few endogenous retroviral elements in the human genome that retain coding sequence. HML-2 expression has been widely associated with human disease states, including different types of cancers as well as with HIV-1 infection. Understanding of the potential impact of this expression requires that it be annotated at the proviral level. Here, we utilized the high throughput capabilities of next-generation sequencing to profile HML-2 expression at the level of individual proviruses and secreted virions in the teratocarcinoma cell line Tera-1. We identified well-defined expression patterns, with transcripts emanating primarily from two proviruses located on chromosome 22, only one of which was efficiently packaged. Interestingly, there was a preference for transcripts of recently integrated proviruses, over those from other highly expressed but older elements, to be packaged into virions. We also assessed the promoter competence of the 5’ long terminal repeats (LTRs of expressed proviruses via a luciferase assay following transfection of Tera-1 cells. Consistent with the RNASeq results, we found that the activity of most LTRs corresponded to their transcript levels.

  19. Control of Epstein-Barr virus infection in vitro by T helper cells specific for virion glycoproteins.

    Science.gov (United States)

    Adhikary, Dinesh; Behrends, Uta; Moosmann, Andreas; Witter, Klaus; Bornkamm, Georg W; Mautner, Josef

    2006-04-17

    Epstein-Barr virus (EBV) establishes lifelong persistent infections in humans by latently infecting B cells, with occasional cycles of reactivation, virus production, and reinfection. Protective immunity against EBV is mediated by T cells, but the role of EBV-specific T helper (Th) cells is still poorly defined. Here, we study the Th response to the EBV lytic cycle proteins BLLF1 (gp350/220), BALF4 (gp110), and BZLF1 and show that glycoprotein-specific Th cells recognize EBV-positive cells directly; surprisingly, a much higher percentage of target cells than those expressing lytic cycle proteins were recognized. Antigen is efficiently transferred to bystander B cells by receptor-mediated uptake of released virions, resulting in recognition of target cells incubated with virus entry before latency is established. Glycoprotein-specific Th cells are cytolytic and inhibit proliferation of lymphoblastoid cell lines (LCL) and the outgrowth of LCL after infection of primary B cells with EBV. These results establish a novel role for glycoprotein-specific Th cells in the control of EBV infection and identify virion proteins as important immune targets. These findings have implications for the treatment of diseases associated with EBV and potentially other coated viruses infecting MHC class II-positive cells.

  20. A G-quadruplex motif in an envelope gene promoter regulates transcription and virion secretion in HBV genotype B.

    Science.gov (United States)

    Biswas, Banhi; Kandpal, Manish; Vivekanandan, Perumal

    2017-09-13

    HBV genotypes differ in pathogenicity. In addition, genotype-specific differences in the regulation of transcription and virus replication exist in HBV, but the underlying mechanisms are unknown. Here, we show the presence of a G-quadruplex motif in the promoter of the preS2/S gene; this G-quadruplex is highly conserved only in HBV genotype B but not in other HBV genotypes. We demonstrate that this G-quadruplex motif forms a hybrid intramolecular G-quadruplex structure. Interestingly, mutations disrupting the G-quadruplex in HBV genotype B reduced the preS2/S promoter activity, leading to reduced hepatitis B surface antigen (HBsAg) levels. G-quadruplex ligands stabilized the G-quadruplex in genotype B and enhanced the preS2/S promoter activity. Furthermore, mutations disrupting the G-quadruplex in the full-length HBV genotype B constructs were associated with impaired virion secretion. In contrast to typical G-quadruplexes within promoters which are negative regulators of transcription the G-quadruplex in the preS2/S promoter of HBV represents an unconventional positive regulatory element. Our findings highlight (a) G-quadruplex mediated enhancement of transcription and virion secretion in HBV and (b) a yet unknown role for DNA secondary structures in complex genotype-specific regulatory mechanisms in virus genomes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. A Next-Generation Sequencing Approach Uncovers Viral Transcripts Incorporated in Poxvirus Virions

    Directory of Open Access Journals (Sweden)

    Marica Grossegesse

    2017-10-01

    Full Text Available Transcripts are known to be incorporated in particles of DNA viruses belonging to the families of Herpesviridae and Mimiviridae, but the presence of transcripts in other DNA viruses, such as poxviruses, has not been analyzed yet. Therefore, we first established a next-generation-sequencing (NGS-based protocol, enabling the unbiased identification of transcripts in virus particles. Subsequently, we applied our protocol to analyze RNA in an emerging zoonotic member of the Poxviridae family, namely Cowpox virus. Our results revealed the incorporation of 19 viral transcripts, while host identifications were restricted to ribosomal and mitochondrial RNA. Most viral transcripts had an unknown and immunomodulatory function, suggesting that transcript incorporation may be beneficial for poxvirus immune evasion. Notably, the most abundant transcript originated from the D5L/I1R gene that encodes a viral inhibitor of the host cytoplasmic DNA sensing machinery.

  2. Studies for the requirements of automatic and remotely controlled shutoff valves on hazardous liquids and natural gas pipelines with respect to public and environmental safety

    Energy Technology Data Exchange (ETDEWEB)

    Oland, C. Barry [XCEL Engineering, Inc. (United States); Rose, Simon D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Engineering Science and Technology Div.; Grant, Herb L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Fabrication, Hoisting and Rigging Div.; Lower, Mark D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Fabrication, Hoisting and Rigging Div.; Spann, Mark A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Facility Management Div.; Kirkpatrick, John R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Computational Sciences and Engineering Div.; Sulfredge, C. David [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Computational Sciences and Engineering Div.

    2012-12-01

    This study assesses the effectiveness of block valve closure swiftness in mitigating the consequences of natural gas and hazardous liquid pipeline releases on public and environmental safety. It also evaluates the technical, operational, and economic feasibility and potential cost benefits of installing automatic shutoff valves (ASVs) and remote control valves (RCVs) in newly constructed and fully replaced transmission lines. Risk analyses of hypothetical pipeline release scenarios are used as the basis for assessing: (1) fire damage to buildings and property in Class 1, Class 2, Class 3, and Class 4 high consequence areas (HCAs) caused by natural gas pipeline releases and subsequent ignition of the released natural gas; (2) fire damage to buildings and property in HCAs designated as high population areas and other populated areas caused by hazardous liquid pipeline releases and subsequent ignition of the released propane; and (3) socioeconomic and environmental damage in HCAs caused by hazardous liquid pipeline releases of crude oil. These risk analyses use engineering principles and fire science practices to characterize thermal radiation effects on buildings and humans and to quantify the total damage cost of socioeconomic and environmental impacts. The risk analysis approach used for natural gas pipelines is consistent with risk assessment standards developed by industry and incorporated into Federal pipeline safety regulations. Feasibility evaluations for the hypothetical pipeline release scenarios considered in this study show that installation of ASVs and RCVs in newly constructed and fully replaced natural gas and hazardous liquid pipelines is technically, operationally, and economically feasible with a positive cost benefit. However, these results may not apply to all newly constructed and fully replaced pipelines because site-specific parameters that influence risk analyses and feasibility evaluations often vary significantly from one pipeline segment to

  3. Features of reovirus outer capsid protein mu1 revealed by electron cryomicroscopy and image reconstruction of the virion at 7.0 Angstrom resolution.

    Science.gov (United States)

    Zhang, Xing; Ji, Yongchang; Zhang, Lan; Harrison, Stephen C; Marinescu, Dan C; Nibert, Max L; Baker, Timothy S

    2005-10-01

    Reovirus is a useful model for addressing the molecular basis of membrane penetration by one of the larger nonenveloped animal viruses. We now report the structure of the reovirus virion at approximately 7.0 A resolution as obtained by electron cryomicroscopy and three-dimensional image reconstruction. Several features of the myristoylated outer capsid protein mu1, not seen in a previous X-ray crystal structure of the mu1-sigma3 heterohexamer, are evident in the virion. These features appear to be important for stabilizing the outer capsid, regulating the conformational changes in mu1 that accompany perforation of target membranes, and contributing directly to membrane penetration during cell entry.

  4. Host entry by gamma-herpesviruses--lessons from animal viruses?

    Science.gov (United States)

    Gillet, Laurent; Frederico, Bruno; Stevenson, Philip G

    2015-12-01

    The oncogenicity of gamma-herpesviruses (γHVs) motivates efforts to control them and their persistence makes early events key targets for intervention. Human γHVs are often assumed to enter naive hosts orally and infect B cells directly. However, neither assumption is supported by direct evidence, and vaccination with the Epstein-Barr virus (EBV) gp350, to block virion binding to B cells, failed to reduce infection rates. Thus, there is a need to re-evaluate assumptions about γHV host entry. Given the difficulty of analysing early human infections, potentially much can be learned from animal models. Genomic comparisons argue that γHVs colonized mammals long before humans speciation, and so that human γHVs are unlikely to differ dramatically in behaviour from those of other mammals. Murid Herpesvirus-4 (MuHV-4), which like EBV and the Kaposi's Sarcoma-associated Herpesvirus (KSHV) persists in memory B cells, enters new hosts via olfactory neurons and exploits myeloid cells to spread. Integrating these data with existing knowledge of human and veterinary γHVs suggests a new model of host entry, with potentially important implications for infection control. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Part II: Oxidative Thermal Aging of Pd/Al2O3 and Pd/CexOy-ZrO2 in Automotive Three Way Catalysts: The Effects of Fuel Shutoff and Attempted Fuel Rich Regeneration

    Directory of Open Access Journals (Sweden)

    Qinghe Zheng

    2015-10-01

    Full Text Available The Pd component in the automotive three way catalyst (TWC experiences deactivation during fuel shutoff, a process employed by automobile companies for enhancing fuel economy when the vehicle is coasting downhill. The process exposes the TWC to a severe oxidative aging environment with the flow of hot (800 °C–1050 °C air. Simulated fuel shutoff aging at 1050 °C leads to Pd metal sintering, the main cause of irreversible deactivation of 3% Pd/Al2O3 and 3% Pd/CexOy-ZrO2 (CZO as model catalysts. The effect on the Rh component was presented in our companion paper Part I. Moderate support sintering and Pd-CexOy interactions were also experienced upon aging, but had a minimal effect on the catalyst activity losses. Cooling in air, following aging, was not able to reverse the metallic Pd sintering by re-dispersing to PdO. Unlike the aged Rh-TWCs (Part I, reduction via in situ steam reforming (SR of exhaust HCs was not effective in reversing the deactivation of aged Pd/Al2O3, but did show a slight recovery of the Pd activity when CZO was the carrier. The Pd+/Pd0 and Ce3+/Ce4+ couples in Pd/CZO are reported to promote the catalytic SR by improving the redox efficiency during the regeneration, while no such promoting effect was observed for Pd/Al2O3. A suggestion is made for improving the catalyst performance.

  6. Congregation of orthopoxvirus virions in cytoplasmic A-type inclusions is mediated by interactions of a bridging protein (A26p) with a matrix protein (ATIp) and a virion membrane-associated protein (A27p).

    Science.gov (United States)

    Howard, Amanda R; Weisberg, Andrea S; Moss, Bernard

    2010-08-01

    Some orthopoxviruses, e.g., the cowpox, ectromelia, and raccoonpox viruses, form large, discrete cytoplasmic inclusions within which mature virions (MVs) are embedded by a process called occlusion. These inclusions, which may protect occluded MVs in the environment, are composed of aggregates of the A-type inclusion protein (ATIp), which is truncated in orthopoxviruses such as vaccinia virus (VACV) and variola virus that fail to form inclusions. In addition to an intact ATIp, occlusion requires the A26 protein (A26p). Although VACV contains a functional A26p, determined by complementation of a cowpox virus occlusion-defective mutant, its role in occlusion was unknown. We found that restoration of the full-length ATI gene was sufficient for VACV inclusion formation and the ensuing occlusion of MVs. A26p was present in inclusions even when virion assembly was inhibited, suggesting a direct interaction of A26p with ATIp. Analysis of a panel of ATIp mutants indicated that the C-terminal repeat region was required for inclusion formation and the N-terminal domain for interaction with A26p and occlusion. A26p is tethered to MVs via interaction with the A27 protein (A27p); A27p was not required for association of A26p with ATIp but was necessary for occlusion. In addition, the C-terminal domain of A26p, which mediates A26p-A27p interactions, was necessary but insufficient for occlusion. Taken together, the data suggest a model for occlusion in which A26p has a bridging role between ATIp and A27p, and A27p provides a link to the MV membrane.

  7. Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export.

    Science.gov (United States)

    Morgan, Gareth W; Hollinshead, Michael; Ferguson, Brian J; Murphy, Brendan J; Carpentier, David C J; Smith, Geoffrey L

    2010-02-26

    Vaccinia virus (VACV) uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC), a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs). Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD) motif, which is conserved in the kinesin-1-binding sequence (KBS) of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.

  8. Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export.

    Directory of Open Access Journals (Sweden)

    Gareth W Morgan

    2010-02-01

    Full Text Available Vaccinia virus (VACV uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC, a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs. Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD motif, which is conserved in the kinesin-1-binding sequence (KBS of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.

  9. The 5’cap of Tobacco Mosaic Virus (TMV) is required for virion attachment to the actin/ER network during early infection

    DEFF Research Database (Denmark)

    Christensen, Nynne Meyn; Tilsner, Jens; Bell, Karen

    and was degraded in the cytoplasm. Removal of the 3’UTR and replicase both inhibited replication but did not prevent granule formation and movement. Dual-labelled TMV virions in which the vRNA and the coat protein were highlighted with different fluorophores showed both fluorescent signals to be initially located...

  10. Image Restoration and Analysis of Influenza Virions Binding to Membrane Receptors Reveal Adhesion-Strengthening Kinetics.

    Directory of Open Access Journals (Sweden)

    Donald W Lee

    Full Text Available With the development of single-particle tracking (SPT microscopy and host membrane mimics called supported lipid bilayers (SLBs, stochastic virus-membrane binding interactions can be studied in depth while maintaining control over host receptor type and concentration. However, several experimental design challenges and quantitative image analysis limitations prevent the widespread use of this approach. One main challenge of SPT studies is the low signal-to-noise ratio of SPT videos, which is sometimes inevitable due to small particle sizes, low quantum yield of fluorescent dyes, and photobleaching. These situations could render current particle tracking software to yield biased binding kinetic data caused by intermittent tracking error. Hence, we developed an effective image restoration algorithm for SPT applications called STAWASP that reveals particles with a signal-to-noise ratio of 2.2 while preserving particle features. We tested our improvements to the SPT binding assay experiment and imaging procedures by monitoring X31 influenza virus binding to α2,3 sialic acid glycolipids. Our interests lie in how slight changes to the peripheral oligosaccharide structures can affect the binding rate and residence times of viruses. We were able to detect viruses binding weakly to a glycolipid called GM3, which was undetected via assays such as surface plasmon resonance. The binding rate was around 28 folds higher when the virus bound to a different glycolipid called GD1a, which has a sialic acid group extending further away from the bilayer surface than GM3. The improved imaging allowed us to obtain binding residence time distributions that reflect an adhesion-strengthening mechanism via multivalent bonds. We empirically fitted these distributions using a time-dependent unbinding rate parameter, koff, which diverges from standard treatment of koff as a constant. We further explain how to convert these models to fit ensemble-averaged binding data

  11. Herpesvirus gB-induced fusion between the virion envelope and outer nuclear membrane during virus egress is regulated by the viral US3 kinase.

    Science.gov (United States)

    Wisner, Todd W; Wright, Catherine C; Kato, Akihisa; Kawaguchi, Yasushi; Mou, Fan; Baines, Joel D; Roller, Richard J; Johnson, David C

    2009-04-01

    Herpesvirus capsids collect along the inner surface of the nuclear envelope and bud into the perinuclear space. Enveloped virions then fuse with the outer nuclear membrane (NM). We previously showed that herpes simplex virus (HSV) glycoproteins gB and gH act in a redundant fashion to promote fusion between the virion envelope and the outer NM. HSV mutants lacking both gB and gH accumulate enveloped virions in herniations, vesicles that bulge into the nucleoplasm. Earlier studies had shown that HSV mutants lacking the viral serine/threonine kinase US3 also accumulate herniations. Here, we demonstrate that HSV gB is phosphorylated in a US3-dependent manner in HSV-infected cells, especially in a crude nuclear fraction. Moreover, US3 directly phosphorylated the gB cytoplasmic (CT) domain in in vitro assays. Deletion of gB in the context of a US3-null virus did not add substantially to defects in nuclear egress. The majority of the US3-dependent phosphorylation of gB involved the CT domain and amino acid T887, a residue present in a motif similar to that recognized by US3 in other proteins. HSV recombinants lacking gH and expressing either gB substitution mutation T887A or a gB truncated at residue 886 displayed substantial defects in nuclear egress. We concluded that phosphorylation of the gB CT domain is important for gB-mediated fusion with the outer NM. This suggested a model in which the US3 kinase is incorporated into the tegument layer (between the capsid and envelope) in HSV virions present in the perinuclear space. By this packaging, US3 might be brought close to the gB CT tail, leading to phosphorylation and triggering fusion between the virion envelope and the outer NM.

  12. The UL13 and US3 Protein Kinases of Herpes Simplex Virus 1 Cooperate to Promote the Assembly and Release of Mature, Infectious Virions.

    Directory of Open Access Journals (Sweden)

    Svetlana Gershburg

    Full Text Available Herpes simplex virus type 1 (HSV-1 encodes two bona fide serine/threonine protein kinases, the US3 and UL13 gene products. HSV-1 ΔUS3 mutants replicate with wild-type efficiency in cultured cells, and HSV-1 ΔUL13 mutants exhibit <10-fold reduction in infectious viral titers. Given these modest phenotypes, it remains unclear how the US3 and UL13 protein kinases contribute to HSV-1 replication. In the current study, we designed a panel of HSV-1 mutants, in which portions of UL13 and US3 genes were replaced by expression cassettes encoding mCherry protein or green fluorescent protein (GFP, respectively, and analyzed DNA replication, protein expression, and spread of these mutants in several cell types. Loss of US3 function alone had largely negligible effect on viral DNA accumulation, gene expression, virion release, and spread. Loss of UL13 function alone also had no appreciable effects on viral DNA levels. However, loss of UL13 function did result in a measurable decrease in the steady-state levels of two viral glycoproteins (gC and gD, release of total and infectious virions, and viral spread. Disruption of both genes did not affect the accumulation of viral DNA, but resulted in further reduction in gC and gD steady-state levels, and attenuation of viral spread and infectious virion release. These data show that the UL13 kinase plays an important role in the late phase of HSV-1 infection, likely by affecting virion assembly and/or release. Moreover, the data suggest that the combined activities of the US3 and UL13 protein kinases are critical to the efficient assembly and release of infectious virions from HSV-1-infected cells.

  13. Comparative Proteomics of Human Monkeypox and Vaccinia Intracellular Mature and Extracellular Enveloped Virions

    Energy Technology Data Exchange (ETDEWEB)

    Manes, Nathan P.; Estep, Ryan D.; Mottaz, Heather M.; Moore, Ronald J.; Clauss, Therese RW; Monroe, Matthew E.; Du, Xiuxia; Adkins, Joshua N.; Wong, Scott; Smith, Richard D.

    2008-03-07

    Orthopoxviruses are the largest and most complex of the animal viruses. In response to the recent emergence of monkeypox in Africa and the threat of smallpox bioterrorism, virulent (monkeypox virus) and benign (vaccinia virus) orthopoxviruses were proteomically compared with the goal of identifying proteins required for pathogenesis. Orthopoxviruses were grown in HeLa cells to two different viral forms (intracellular mature virus and extracellular enveloped virus), purified by sucrose gradient ultracentrifugation, denatured using RapiGest™ surfactant, and digested with trypsin. Unfractionated samples and strong cation exchange HPLC fractions were analyzed by reversed-phase LC-MS/MS, and analyses of the MS/MS spectra using SEQUEST® and X! Tandem resulted in the identification of hundreds of monkeypox, vaccinia, and copurified host proteins. The unfractionated samples were additionally analyzed by LC-MS on an LTQ-Orbitrap™, and the accurate mass and elution time tag approach was used to perform quantitative comparisons. Possible pathophysiological roles of differentially expressed orthopoxvirus genes are discussed.

  14. The Effect of Hydrogen Sulfide Concentration on Gel as Water Shutoff Agent Effet de la concentration en sulfure d'hydrogène sur un gel utilisé en tant qu'agent de traitement des venues d'eaux

    OpenAIRE

    You Q.; Mu L.; Wang Y.; Zhao F.

    2011-01-01

    For drilling and water shutoff of oil and gas reservoirs containing hydrogen sulfide (H2S), the effects of H2S on widely used gel as water shutoff agents are studied. The gels include Na2Cr2O7/Na2SO3/HPAM gel, Na2Cr2O7/(NH2)2CS/HPAM gel, Cr(III)-acetate & Cr(III)-lactate/HPAM gel and phenol formaldehyde resin/HPAM gel. The results show that: for Na2Cr2O7/Na2SO3/HPAM gel and Na2Cr2O7/(NH2)2CS/HPAM gel, the H2S as reducing agent (the reducibility is more efficient than that of Na2SO3a...

  15. A genetic system for Citrus Tristeza Virus using the non-natural host Nicotiana benthamiana: an update

    Directory of Open Access Journals (Sweden)

    Silvia eAmbrós

    2013-07-01

    Full Text Available In nature Citrus tristeza virus (CTV, genus Closterovirus, infects only the phloem cells of species of Citrus and related genera. Finding that the CTV T36 strain replicated in Nicotiana benthamiana (NB protoplasts and produced normal virions allowed development of the first genetic system based on protoplast transfection with RNA transcribed from a full-genome cDNA clone, a laborious and uncertain system requiring several months for each experiment. We developed a more efficient system based on agroinfiltration of NB leaves with CTV-T36-based binary plasmids, which caused systemic infection in this non-natural host within a few weeks yielding in the upper leaves enough CTV virions to readily infect citrus by slash inoculation. Stem agroinoculation of citrus and NB plants with oncogenic strains of Agrobacterium tumefaciens carrying a CTV-T36 binary vector with a GUS marker, induced GUS positive galls in both species. However, while most NB tumours were CTV positive and many plants became systemically infected, no coat protein or viral RNA was detected in citrus tumours, even though CTV cDNA was readily detected by PCR in the same galls. This finding suggests i strong silencing or CTV RNA processing in transformed cells impairing infection progress, and ii the need for using NB as an intermediate host in the genetic system. To maintain CTV-T36 in NB or assay other CTV genotypes in this host, we also tried to graft-transmit the virus from infected to healthy NB, or to mechanically inoculate NB leaves with virion extracts. While these trials were mostly unsuccessful on non-treated NB plants, agroinfiltration with silencing suppressors enabled for the first time infecting NB plants by side-grafting and by mechanical inoculation with virions, indicating that previous failure to infect NB was likely due to virus silencing in early infection steps. Using NB as a CTV host provides new possibilities to study virus-host interactions with a simple and

  16. Antagonism of host antiviral responses by Kaposi's sarcoma-associated herpesvirus tegument protein ORF45.

    Directory of Open Access Journals (Sweden)

    Fan Xiu Zhu

    2010-05-01

    Full Text Available Virus infection of a cell generally evokes an immune response by the host to defeat the intruder in its effort. Many viruses have developed an array of strategies to evade or antagonize host antiviral responses. Kaposi's sarcoma-associated herpesvirus (KSHV is demonstrated in this report to be able to prevent activation of host antiviral defense mechanisms upon infection. Cells infected with wild-type KSHV were permissive for superinfection with vesicular stomatitis virus (VSV, suggesting that KSHV virions fail to induce host antiviral responses. We previously showed that ORF45, a KSHV immediate-early protein as well as a tegument protein of virions, interacts with IRF-7 and inhibits virus-mediated type I interferon induction by blocking IRF-7 phosphorylation and nuclear translocation (Zhu et al., Proc. Natl. Acad. Sci. USA. 99:5573-5578, 2002. Here, using an ORF45-null recombinant virus, we demonstrate a profound role of ORF45 in inhibiting host antiviral responses. Infection of cells with an ORF45-null mutant recombinant KSHV (BAC-stop45 triggered an immune response that resisted VSV super-infection, concomitantly associated with appreciable increases in transcription of type I IFN and downstream anti-viral effector genes. Gain-of-function analysis showed that ectopic expression of ORF45 in human fibroblast cells by a lentivirus vector decreased the antiviral responses of the cells. shRNA-mediated silencing of IRF-7, that predominantly regulates both the early and late phase induction of type I IFNs, clearly indicated its critical contribution to the innate antiviral responses generated against incoming KSHV particles. Thus ORF45 through its targeting of the crucial IRF-7 regulated type I IFN antiviral responses significantly contributes to the KSHV survival immediately following a primary infection allowing for progression onto subsequent stages in its life-cycle.

  17. FSL constructs: a simple method for modifying cell/virion surfaces with a range of biological markers without affecting their viability.

    Science.gov (United States)

    Blake, Deborah A; Bovin, Nicolai V; Bess, Dan; Henry, Stephen M

    2011-08-05

    The ability to modify/visualize biological surfaces, and then study the modified cell/virion in a range of in vitro and in vivo environments is essential to gaining further insight into the function of specific molecules or the entire entity. Studies of biological surface modification are generally limited to genetic engineering of the organism or the covalent attachment of chemical moieties to the cell surface(1,2). However these traditional techniques expose the cell to chemical reactants, or they require significant manipulation to achieve the desired outcome, making them cumbersome, and they may also inadvertently affect the viability/functionality of the modified cell. A simple method to harmlessly modify the surface of cells is required. Recently a new technology, KODE Technology has introduced a range of novel constructs consisting of three components: a functional head group (F), a spacer (S) and a lipid tail (L) and are known as Function-Spacer-Lipid or FSL constructs3. The spacer (S) is selected to provide a construct that is dispersible in water, yet will spontaneously and stably incorporate into a membrane. FSL construct functional moieties (F) so far include a range of saccharides including blood group-related determinants, sialic acids, hyaluronan polysaccharides, fluorophores, biotin, radiolabels, and a range of peptides(3-12). FSL constructs have been used in modifying embryos, spermatozoa, zebrafish, epithelial/endometrial cells, red blood cells, and virions to create quality controls systems and diagnostic panels, to modify cell adhesion/ interaction/ separation/ immobilization, and for in vitro and in vivo imaging of cells/virions(3-12). The process of modifying cells/virions is generic and extremely simple. The most common procedure is incubation of cells (in lipid free media) with a solution for FSL constructs for 1-2 hours at 37°C(4-10). During the incubation the FSL constructs spontaneously incorporate into the membrane, and the process is

  18. Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis, Leading to Retention of the Scaffold Protein and Mislocalization of Membrane-Associated Entry Proteins.

    Science.gov (United States)

    Hyun, Seong-In; Weisberg, Andrea; Moss, Bernard

    2017-08-01

    The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino-acid protein with a putative C-terminal transmembrane domain. Previous studies with a tetracycline-inducible mutant demonstrated that I2-deficient virions are defective in cell entry. The purpose of the present study was to determine the step of replication or entry that is affected by loss of the I2 protein. Fluorescence microscopy experiments showed that I2 colocalized with a major membrane protein of immature and mature virions. We generated a cell line that constitutively expressed I2 and allowed construction of the VACV I2L deletion mutant vΔI2. As anticipated, vΔI2 was unable to replicate in cells that did not express I2. Unexpectedly, morphogenesis was interrupted at a stage after immature virion formation, resulting in the accumulation of dense spherical particles instead of brick-shaped mature virions with well-defined core structures. The abnormal particles retained the D13 scaffold protein of immature virions, were severely deficient in the transmembrane proteins that comprise the entry fusion complex (EFC), and had increased amounts of unprocessed membrane and core proteins. Total lysates of cells infected with vΔI2 also had diminished EFC proteins due to instability attributed to their hydrophobicity and failure to be inserted into viral membranes. A similar instability of EFC proteins had previously been found with unrelated mutants blocked earlier in morphogenesis that also accumulated viral membranes retaining the D13 scaffold. We concluded that I2 is required for virion morphogenesis, release of the D13 scaffold, and the association of EFC proteins with viral membranes.IMPORTANCE Poxviruses comprise a large family that infect vertebrates and invertebrates, cause disease in both in humans and in wild and domesticated animals, and are being engineered as vectors for vaccines and cancer therapy. In addition, investigations of poxviruses have provided insights into many

  19. TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions

    Science.gov (United States)

    Das, Anshuman; Hirai-Yuki, Asuka; González-López, Olga; Rhein, Bethany; Moller-Tank, Sven; Brouillette, Rachel; Hensley, Lucinda; Misumi, Ichiro; Lovell, William; Cullen, John M.; Whitmire, Jason K.; Maury, Wendy

    2017-01-01

    ABSTRACT Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV) attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer) residues on the eHAV membrane. Both Tim1−/− Ifnar1−/− and Tim4−/− Ifnar1−/− double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT) elevations similar to those in Ifnar1−/− mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1−/−Ifnar1−/− mice compared to Ifnar1−/− mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice. PMID:28874468

  20. TIM1 (HAVCR1 Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions

    Directory of Open Access Journals (Sweden)

    Anshuman Das

    2017-09-01

    Full Text Available Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1 is widely accepted to be the receptor for hepatitis A virus (HAV, an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer residues on the eHAV membrane. Both Tim1−/− Ifnar1−/− and Tim4−/− Ifnar1−/− double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT elevations similar to those in Ifnar1−/− mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1−/−Ifnar1−/− mice compared to Ifnar1−/− mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice.

  1. Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding.

    Science.gov (United States)

    Panico, Maria; Bouché, Laura; Binet, Daniel; O'Connor, Michael-John; Rahman, Dinah; Pang, Poh-Choo; Canis, Kevin; North, Simon J; Desrosiers, Ronald C; Chertova, Elena; Keele, Brandon F; Bess, Julian W; Lifson, Jeffrey D; Haslam, Stuart M; Dell, Anne; Morris, Howard R

    2016-09-08

    The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120(SU) plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this "glycan shield" can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens.

  2. Palmitoylation of the feline immunodeficiency virus envelope glycoprotein and its effect on fusion activity and envelope incorporation into virions

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, Silvia A.; Paladino, Monica G. [Laboratorio de Virologia, CONICET-Universidad de Belgrano (UB), Villanueva 1324 (C1426BMJ), Buenos Aires (Argentina); Affranchino, Jose L., E-mail: jose.affranchino@comunidad.ub.edu.ar [Laboratorio de Virologia, CONICET-Universidad de Belgrano (UB), Villanueva 1324 (C1426BMJ), Buenos Aires (Argentina)

    2012-06-20

    The feline immunodeficiency virus (FIV) envelope glycoprotein (Env) possesses a short cytoplasmic domain of 53 amino acids containing four highly conserved cysteines at Env positions 804, 811, 815 and 848. Since palmitoylation of transmembrane proteins occurs at or near the membrane anchor, we investigated whether cysteines 804, 811 and 815 are acylated and analyzed the relevance of these residues for Env functions. Replacement of cysteines 804, 811 and 815 individually or in combination by serine residues resulted in Env glycoproteins that were efficiently expressed and processed. However, mutations C804S and C811S reduced Env fusogenicity by 93% and 84%, respectively, compared with wild-type Env. By contrast, mutant C815S exhibited a fusogenic capacity representing 50% of the wild-type value. Remarkably, the double mutation C804S/C811S abrogated both Env fusion activity and Env incorporation into virions. Finally, by means of Click chemistry assays we demonstrated that the four FIV Env cytoplasmic cysteines are palmitoylated.

  3. Features of Reovirus Outer Capsid Protein μ1 Revealed by Electron Cryomicroscopy and Image Reconstruction of the Virion at 7.0 Å Resolution

    Science.gov (United States)

    Zhang, Xing; Ji, Yongchang; Zhang, Lan; Harrison, Stephen C.; Marinescu, Dan C.; Nibert, Max L.; Baker, Timothy S.

    2014-01-01

    Summary Reovirus is a useful model for addressing the molecular basis of membrane penetration by one of the larger nonenveloped animal viruses. We now report the structure of the reovirus virion at 7.0 Å resolution as obtained by electron cryomicroscopy and three-dimensional image reconstruction. Several features of the myristoylated outer capsid protein μ1, not seen in a previous X-ray crystal structure of the μ1-σ3 heterohexamer, are evident in the virion. These features appear to be important for stabilizing the outer capsid, regulating the conformational changes in μ1 that accompany perforation of target membranes, and contributing directly to membrane penetration during cell entry. PMID:16216585

  4. Virocell Metabolism: Metabolic Innovations During Host-Virus Interactions in the Ocean.

    Science.gov (United States)

    Rosenwasser, Shilo; Ziv, Carmit; Creveld, Shiri Graff van; Vardi, Assaf

    2016-10-01

    Marine viruses are considered to be major ecological, evolutionary, and biogeochemical drivers of the marine environment, responsible for nutrient recycling and determining species composition. Viruses can re-shape their host's metabolic network during infection, generating the virocell-a unique metabolic state that supports their specific requirement. Here we discuss the concept of 'virocell metabolism' and its formation by rewiring of host-encoded metabolic networks, or by introducing virus-encoded auxiliary metabolic genes which provide the virocell with novel metabolic capabilities. The ecological role of marine viruses is commonly assessed by their relative abundance and phylogenetic diversity, lacking the ability to assess the dynamics of active viral infection. The new ability to define a unique metabolic state of the virocell will expand the current virion-centric approaches in order to quantify the impact of marine viruses on microbial food webs. Copyright © 2016. Published by Elsevier Ltd.

  5. Comparison of effects of adjuvants on efficacy of virion envelope herpes simplex virus vaccine against labial infection of BALB/c mice.

    OpenAIRE

    Thomson, T A; Hilfenhaus, J; Moser, H; Morahan, P S

    1983-01-01

    A subunit virion envelope vaccine of herpes simplex virus type 1 was evaluated for its ability to protect labially infected mice from development of the primary herpetic lesion, encephalitic death, and latent virus infection in the trigeminal ganglion. Several adjuvants, including aluminum hydroxide and polyriboinosinic acid-polyribocytidylic acid complexed with poly-L-lysine and carboxymethyl cellulose were investigated for their ability to enhance protection of the subunit vaccine and were ...

  6. Herpes simplex virus glycoproteins gB and gH function in fusion between the virion envelope and the outer nuclear membrane.

    Science.gov (United States)

    Farnsworth, Aaron; Wisner, Todd W; Webb, Michael; Roller, Richard; Cohen, Gary; Eisenberg, Roselyn; Johnson, David C

    2007-06-12

    Herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. It is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (NM). To reach the cytoplasm these enveloped particles must fuse with the outer NM and the unenveloped capsids then acquire a second envelope in the trans-Golgi network. Little is known about the process by which herpesviruses virions fuse with the outer NM. Here we show that a herpes simplex virus (HSV) mutant lacking both the two putative fusion glycoproteins gB and gH failed to cross the nuclear envelope. Enveloped virions accumulated in the perinuclear space or in membrane vesicles that bulged into the nucleoplasm (herniations). By contrast, mutants lacking just gB or gH showed only minor or no defects in nuclear egress. We concluded that either HSV gB or gH can promote fusion between the virion envelope and the outer NM. It is noteworthy that fusion associated with HSV entry requires the cooperative action of both gB and gH, suggesting that the two types of fusion (egress versus entry) are dissimilar processes.

  7. Three-dimensional visualization of the Autographa californica multiple nucleopolyhedrovirus occlusion-derived virion envelopment process gives new clues as to its mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yang; Li, Kunpeng [State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou (China); Tang, Peiping [State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou (China); Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui (China); Li, Yinyin; Zhou, Qiang; Yang, Kai [State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou (China); Zhang, Qinfen, E-mail: lsszqf@mail.sysu.edu.cn [State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou (China)

    2015-02-15

    Baculoviruses produce two virion phenotypes, occlusion-derived virion (ODV) and budded virion (BV). ODV envelopment occurs in the nucleus. Morphogenesis of the ODV has been studied extensively; however, the mechanisms underlying microvesicle formation and ODV envelopment in nuclei remain unclear. In this study, we used electron tomography (ET) together with the conventional electron microscopy to study the envelopment of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ODV. Our results demonstrate that not only the inner but also the outer nuclear membrane can invaginate and vesiculate into microvesicles and that intranuclear microvesicles are the direct source of the ODV membrane. Five main events in the ODV envelopment process are summarized, from which we propose a model to explain this process. - Highlights: • Both the inner and outer nuclear membranes could invaginate. • Both the inner and outer nuclear membranes could vesiculate into microvesicles. • Five main events in the ODV envelopment process are summarized. • A model is proposed to explain this ODV envelopment.

  8. Determining host metabolic limitations on viral replication via integrated modeling and experimental perturbation.

    Directory of Open Access Journals (Sweden)

    Elsa W Birch

    Full Text Available Viral replication relies on host metabolic machinery and precursors to produce large numbers of progeny - often very rapidly. A fundamental example is the infection of Escherichia coli by bacteriophage T7. The resource draw imposed by viral replication represents a significant and complex perturbation to the extensive and interconnected network of host metabolic pathways. To better understand this system, we have integrated a set of structured ordinary differential equations quantifying T7 replication and an E. coli flux balance analysis metabolic model. Further, we present here an integrated simulation algorithm enforcing mutual constraint by the models across the entire duration of phage replication. This method enables quantitative dynamic prediction of virion production given only specification of host nutritional environment, and predictions compare favorably to experimental measurements of phage replication in multiple environments. The level of detail of our computational predictions facilitates exploration of the dynamic changes in host metabolic fluxes that result from viral resource consumption, as well as analysis of the limiting processes dictating maximum viral progeny production. For example, although it is commonly assumed that viral infection dynamics are predominantly limited by the amount of protein synthesis machinery in the host, our results suggest that in many cases metabolic limitation is at least as strict. Taken together, these results emphasize the importance of considering viral infections in the context of host metabolism.

  9. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein.

    Science.gov (United States)

    Khamina, Kseniya; Lercher, Alexander; Caldera, Michael; Schliehe, Christopher; Vilagos, Bojan; Sahin, Mehmet; Kosack, Lindsay; Bhattacharya, Anannya; Májek, Peter; Stukalov, Alexey; Sacco, Roberto; James, Leo C; Pinschewer, Daniel D; Bennett, Keiryn L; Menche, Jörg; Bergthaler, Andreas

    2017-12-01

    RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics. A subsequent mass-spectrometric analysis of L protein pulldowns from infected human cells revealed a comprehensive network of interacting host proteins. The obtained LCMV L protein interactome was bioinformatically integrated with known host protein interactors of RdRps from other RNA viruses, emphasizing interconnected modules of human proteins. Functional characterization of selected interactors highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors. To corroborate these findings, we infected Trim21-/- mice with LCMV and found impaired virus control in chronic infection. These results provide insights into the complex interactions of the arenavirus LCMV and other viral RdRps with the host proteome and contribute to a better molecular understanding of how chronic viruses interact with their host.

  10. Within-host spatiotemporal dynamics of plant virus infection at the cellular level.

    Directory of Open Access Journals (Sweden)

    Nicolas Tromas

    2014-02-01

    Full Text Available A multicellular organism is not a monolayer of cells in a flask; it is a complex, spatially structured environment, offering both challenges and opportunities for viruses to thrive. Whereas virus infection dynamics at the host and within-cell levels have been documented, the intermediate between-cell level remains poorly understood. Here, we used flow cytometry to measure the infection status of thousands of individual cells in virus-infected plants. This approach allowed us to determine accurately the number of cells infected by two virus variants in the same host, over space and time as the virus colonizes the host. We found a low overall frequency of cellular infection (<0.3, and few cells were coinfected by both virus variants (<0.1. We then estimated the cellular contagion rate (R, the number of secondary infections per infected cell per day. R ranged from 2.43 to values not significantly different from zero, and generally decreased over time. Estimates of the cellular multiplicity of infection (MOI, the number of virions infecting a cell, were low (<1.5. Variance of virus-genotype frequencies increased strongly from leaf to cell levels, in agreement with a low MOI. Finally, there were leaf-dependent differences in the ease with which a leaf could be colonized, and the number of virions effectively colonizing a leaf. The modeling of infection patterns suggests that the aggregation of virus-infected cells plays a key role in limiting spread; matching the observation that cell-to-cell movement of plant viruses can result in patches of infection. Our results show that virus expansion at the between-cell level is restricted, probably due to the host environment and virus infection itself.

  11. Host age modulates within-host parasite competition

    OpenAIRE

    Izhar, Rony; Routtu, Jarkko; Ben-Ami, Frida

    2015-01-01

    In many host populations, one of the most striking differences among hosts is their age. While parasite prevalence differences in relation to host age are well known, little is known on how host age impacts ecological and evolutionary dynamics of diseases. Using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa, we examined how host age at exposure influences within-host parasite competition and virulence. We found that multiply-exposed hosts...

  12. Formation of orthopoxvirus cytoplasmic A-type inclusion bodies and embedding of virions are dynamic processes requiring microtubules.

    Science.gov (United States)

    Howard, Amanda R; Moss, Bernard

    2012-05-01

    In cells infected with some orthopoxviruses, numerous mature virions (MVs) become embedded within large, cytoplasmic A-type inclusions (ATIs) that can protect infectivity after cell lysis. ATIs are composed of an abundant viral protein called ATIp, which is truncated in orthopoxviruses such as vaccinia virus (VACV) that do not form ATIs. To study ATI formation and occlusion of MVs within ATIs, we used recombinant VACVs that express the cowpox full-length ATIp or we transfected plasmids encoding ATIp into cells infected with VACV, enabling ATI formation. ATI enlargement and MV embedment required continued protein synthesis and an intact microtubular network. For live imaging of ATIs and MVs, plasmids expressing mCherry fluorescent protein fused to ATIp were transfected into cells infected with VACV expressing the viral core protein A4 fused to yellow fluorescent protein. ATIs appeared as dynamic, mobile bodies that enlarged by multiple coalescence events, which could be prevented by disrupting microtubules. Coalescence of ATIs was confirmed in cells infected with cowpox virus. MVs were predominantly at the periphery of ATIs early in infection. We determined that coalescence contributed to the distribution of MVs within ATIs and that microtubule-disrupting drugs abrogated coalescence-mediated MV embedment. In addition, MVs were shown to move from viral factories at speeds consistent with microtubular transport to the peripheries of ATIs, whereas disruption of microtubules prevented such trafficking. The data indicate an important role for microtubules in the coalescence of ATIs into larger structures, transport of MVs to ATIs, and embedment of MVs within the ATI matrix.

  13. Two potential recombinant rabies vaccines expressing canine parvovirus virion protein 2 induce immunogenicity to canine parvovirus and rabies virus.

    Science.gov (United States)

    Luo, Jun; Shi, Hehe; Tan, Yeping; Niu, Xuefeng; Long, Teng; Zhao, Jing; Tian, Qin; Wang, Yifei; Chen, Hao; Guo, Xiaofeng

    2016-08-17

    Both rabies virus (RABV) and canine parvovirus (CPV) cause lethal diseases in dogs. In this study, both high egg passage Flury (HEP-Flury) strains of RABV and recombinant RABV carrying double RABV glycoprotein (G) gene were used to express the CPV virion protein 2 (VP2) gene, and were designated rHEP-VP2 and, rHEP-dG-VP2 respectively. The two recombinant RABVs maintained optimal virus titration according to their viral growth kinetics assay compared with the parental strain HEP-Flury. Western blotting indicated that G protein and VP2 were expressed in vitro. The expression of VP2 in Crandell feline kidney cells post-infection by rHEP-VP2 and rHEP-dG-VP2 was confirmed by indirect immunofluorescence assay with antibody against VP2. Immunogenicity of recombinant rabies viruses was tested in Kunming mice. Both rHEP-VP2 and rHEP-dG-VP2 induced high levels of rabies antibody compared with HEP-Flury. Mice immunized with rHEP-VP2 and rHEP-dG-VP2 both had a high level of antibodies against VP2, which can protect against CPV infection. A challenge experiment indicated that more than 80% mice immunized with recombinant RABVs survived after infection of challenge virus standard 24 (CVS-24). Together, this study showed that recombinant RABVs expressing VP2 induced protective immune responses to RABV and CPV. Therefore, rHEP-VP2 and rHEP-dG-VP2 might be potential combined vaccines for RABV and CPV. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Picornavirus RNA is protected from cleavage by ribonuclease during virion uncoating and transfer across cellular and model membranes.

    Directory of Open Access Journals (Sweden)

    Elisabetta Groppelli

    2017-02-01

    Full Text Available Picornaviruses are non-enveloped RNA viruses that enter cells via receptor-mediated endocytosis. Because they lack an envelope, picornaviruses face the challenge of delivering their RNA genomes across the membrane of the endocytic vesicle into the cytoplasm to initiate infection. Currently, the mechanism of genome release and translocation across membranes remains poorly understood. Within the enterovirus genus, poliovirus, rhinovirus 2, and rhinovirus 16 have been proposed to release their genomes across intact endosomal membranes through virally induced pores, whereas one study has proposed that rhinovirus 14 releases its RNA following disruption of endosomal membranes. For the more distantly related aphthovirus genus (e.g. foot-and-mouth disease viruses and equine rhinitis A virus acidification of endosomes results in the disassembly of the virion into pentamers and in the release of the viral RNA into the lumen of the endosome, but no details have been elucidated as how the RNA crosses the vesicle membrane. However, more recent studies suggest aphthovirus RNA is released from intact particles and the dissociation to pentamers may be a late event. In this study we have investigated the RNase A sensitivity of genome translocation of poliovirus using a receptor-decorated-liposome model and the sensitivity of infection of poliovirus and equine-rhinitis A virus to co-internalized RNase A. We show that poliovirus genome translocation is insensitive to RNase A and results in little or no release into the medium in the liposome model. We also show that infectivity is not reduced by co-internalized RNase A for poliovirus and equine rhinitis A virus. Additionally, we show that all poliovirus genomes that are internalized into cells, not just those resulting in infection, are protected from RNase A. These results support a finely coordinated, directional model of viral RNA delivery that involves viral proteins and cellular membranes.

  15. The encapsidated genome of Microplitis demolitor bracovirus integrates into the host Pseudoplusia includens.

    Science.gov (United States)

    Beck, Markus H; Zhang, Shu; Bitra, Kavita; Burke, Gaelen R; Strand, Michael R

    2011-11-01

    Polydnaviruses (PDVs) are symbionts of parasitoid wasps that function as gene delivery vehicles in the insects (hosts) that the wasps parasitize. PDVs persist in wasps as integrated proviruses but are packaged as circularized and segmented double-stranded DNAs into the virions that wasps inject into hosts. In contrast, little is known about how PDV genomic DNAs persist in host cells. Microplitis demolitor carries Microplitis demolitor bracovirus (MdBV) and parasitizes the host Pseudoplusia includens. MdBV infects primarily host hemocytes and also infects a hemocyte-derived cell line from P. includens called CiE1 cells. Here we report that all 15 genomic segments of the MdBV encapsidated genome exhibited long-term persistence in CiE1 cells. Most MdBV genes expressed in hemocytes were persistently expressed in CiE1 cells, including members of the glc gene family whose products transformed CiE1 cells into a suspension culture. PCR-based integration assays combined with cloning and sequencing of host-virus junctions confirmed that genomic segments J and C persisted in CiE1 cells by integration. These genomic DNAs also rapidly integrated into parasitized P. includens. Sequence analysis of wasp-viral junction clones showed that the integration of proviral segments in M. demolitor was associated with a wasp excision/integration motif (WIM) known from other bracoviruses. However, integration into host cells occurred in association with a previously unknown domain that we named the host integration motif (HIM). The presence of HIMs in most MdBV genomic DNAs suggests that the integration of each genomic segment into host cells occurs through a shared mechanism.

  16. The Encapsidated Genome of Microplitis demolitor Bracovirus Integrates into the Host Pseudoplusia includens ▿ ‡

    Science.gov (United States)

    Beck, Markus H.; Zhang, Shu; Bitra, Kavita; Burke, Gaelen R.; Strand, Michael R.

    2011-01-01

    Polydnaviruses (PDVs) are symbionts of parasitoid wasps that function as gene delivery vehicles in the insects (hosts) that the wasps parasitize. PDVs persist in wasps as integrated proviruses but are packaged as circularized and segmented double-stranded DNAs into the virions that wasps inject into hosts. In contrast, little is known about how PDV genomic DNAs persist in host cells. Microplitis demolitor carries Microplitis demolitor bracovirus (MdBV) and parasitizes the host Pseudoplusia includens. MdBV infects primarily host hemocytes and also infects a hemocyte-derived cell line from P. includens called CiE1 cells. Here we report that all 15 genomic segments of the MdBV encapsidated genome exhibited long-term persistence in CiE1 cells. Most MdBV genes expressed in hemocytes were persistently expressed in CiE1 cells, including members of the glc gene family whose products transformed CiE1 cells into a suspension culture. PCR-based integration assays combined with cloning and sequencing of host-virus junctions confirmed that genomic segments J and C persisted in CiE1 cells by integration. These genomic DNAs also rapidly integrated into parasitized P. includens. Sequence analysis of wasp-viral junction clones showed that the integration of proviral segments in M. demolitor was associated with a wasp excision/integration motif (WIM) known from other bracoviruses. However, integration into host cells occurred in association with a previously unknown domain that we named the host integration motif (HIM). The presence of HIMs in most MdBV genomic DNAs suggests that the integration of each genomic segment into host cells occurs through a shared mechanism. PMID:21880747

  17. Cyclin F/FBXO1 Interacts with HIV-1 Viral Infectivity Factor (Vif) and Restricts Progeny Virion Infectivity by Ubiquitination and Proteasomal Degradation of Vif Protein through SCF(cyclin F) E3 Ligase Machinery.

    Science.gov (United States)

    Augustine, Tracy; Chaudhary, Priyanka; Gupta, Kailash; Islam, Sehbanul; Ghosh, Payel; Santra, Manas Kumar; Mitra, Debashis

    2017-03-31

    Cyclin F protein, also known as FBXO1, is the largest among all cyclins and oscillates in the cell cycle like other cyclins. Apart from being a G2/M cyclin, cyclin F functions as the substrate-binding subunit of SCF(cyclin F) E3 ubiquitin ligase. In a gene expression analysis performed to identify novel gene modulations associated with cell cycle dysregulation during HIV-1 infection in CD4(+) T cells, we observed down-regulation of the cyclin F gene (CCNF). Later, using gene overexpression and knockdown studies, we identified cyclin F as negatively influencing HIV-1 viral infectivity without any significant impact on virus production. Subsequently, we found that cyclin F negatively regulates the expression of viral protein Vif (viral infectivity factor) at the protein level. We also identified a novel host-pathogen interaction between cyclin F and Vif protein in T cells during HIV-1 infection. Mutational analysis of a cyclin F-specific amino acid motif in the C-terminal region of Vif indicated rescue of the protein from cyclin F-mediated down-regulation. Subsequently, we showed that Vif is a novel substrate of the SCF(cyclin F) E3 ligase, where cyclin F mediates the ubiquitination and proteasomal degradation of Vif through physical interaction. Finally, we showed that cyclin F augments APOBEC3G expression through degradation of Vif to regulate infectivity of progeny virions. Taken together, our results demonstrate that cyclin F is a novel F-box protein that functions as an intrinsic cellular regulator of HIV-1 Vif and has a negative regulatory effect on the maintenance of viral infectivity by restoring APOBEC3G expression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Host ESCRT proteins are required for bromovirus RNA replication compartment assembly and function.

    Directory of Open Access Journals (Sweden)

    Arturo Diaz

    2015-03-01

    Full Text Available Positive-strand RNA viruses genome replication invariably is associated with vesicles or other rearranged cellular membranes. Brome mosaic virus (BMV RNA replication occurs on perinuclear endoplasmic reticulum (ER membranes in ~70 nm vesicular invaginations (spherules. BMV RNA replication vesicles show multiple parallels with membrane-enveloped, budding retrovirus virions, whose envelopment and release depend on the host ESCRT (endosomal sorting complexes required for transport membrane-remodeling machinery. We now find that deleting components of the ESCRT pathway results in at least two distinct BMV phenotypes. One group of genes regulate RNA replication and the frequency of viral replication complex formation, but had no effect on spherule size, while a second group of genes regulate RNA replication in a way or ways independent of spherule formation. In particular, deleting SNF7 inhibits BMV RNA replication > 25-fold and abolishes detectable BMV spherule formation, even though the BMV RNA replication proteins accumulate and localize normally on perinuclear ER membranes. Moreover, BMV ESCRT recruitment and spherule assembly depend on different sets of protein-protein interactions from those used by multivesicular body vesicles, HIV-1 virion budding, or tomato bushy stunt virus (TBSV spherule formation. These and other data demonstrate that BMV requires cellular ESCRT components for proper formation and function of its vesicular RNA replication compartments. The results highlight growing but diverse interactions of ESCRT factors with many viruses and viral processes, and potential value of the ESCRT pathway as a target for broad-spectrum antiviral resistance.

  19. Disassembly and reassembly of human papillomavirus virus-like particles produces more virion-like antibody reactivity

    Directory of Open Access Journals (Sweden)

    Zhao Qinjian

    2012-02-01

    Full Text Available Abstract Background Human papillomavirus (HPV vaccines based on major capsid protein L1 are licensed in over 100 countries to prevent HPV infections. The yeast-derived recombinant quadrivalent HPV L1 vaccine, GARDASIL(R, has played an important role in reducing cancer and genital warts since its introduction in 2006. The L1 proteins self-assemble into virus-like particles (VLPs. Results VLPs were subjected to post-purification disassembly and reassembly (D/R treatment during bioprocessing to improve VLP immunoreactivity and stability. The post-D/R HPV16 VLPs and their complex with H16.V5 neutralizing antibody Fab fragments were visualized by cryo electron microscopy, showing VLPs densely decorated with antibody. Along with structural improvements, post-D/R VLPs showed markedly higher antigenicity to conformational and neutralizing monoclonal antibodies (mAbs H16.V5, H16.E70 and H263.A2, whereas binding to mAbs recognizing linear epitopes (H16.J4, H16.O7, and H16.H5 was greatly reduced. Strikingly, post-D/R VLPs showed no detectable binding to H16.H5, indicating that the H16.H5 epitope is not accessible in fully assembled VLPs. An atomic homology model of the entire HPV16 VLP was generated based on previously determined high-resolution structures of bovine papillomavirus and HPV16 L1 pentameric capsomeres. Conclusions D/R treatment of HPV16 L1 VLPs produces more homogeneous VLPs with more virion-like antibody reactivity. These effects can be attributed to a combination of more complete and regular assembly of the VLPs, better folding of L1, reduced non-specific disulfide-mediated aggregation and increased stability of the VLPs. Markedly different antigenicity of HPV16 VLPs was observed upon D/R treatment with a panel of monoclonal antibodies targeting neutralization sensitive epitopes. Multiple epitope-specific assays with a panel of mAbs with different properties and epitopes are required to gain a better understanding of the immunochemical

  20. Retrograde Transport from Early Endosomes to the trans-Golgi Network Enables Membrane Wrapping and Egress of Vaccinia Virus Virions.

    Science.gov (United States)

    Sivan, Gilad; Weisberg, Andrea S; Americo, Jeffrey L; Moss, Bernard

    2016-10-01

    The anterograde pathway, from the endoplasmic reticulum through the trans-Golgi network to the cell surface, is utilized by trans-membrane and secretory proteins. The retrograde pathway, which directs traffic in the opposite direction, is used following endocytosis of exogenous molecules and recycling of membrane proteins. Microbes exploit both routes: viruses typically use the anterograde pathway for envelope formation prior to exiting the cell, whereas ricin and Shiga-like toxins and some nonenveloped viruses use the retrograde pathway for cell entry. Mining a human genome-wide RNA interference (RNAi) screen revealed a need for multiple retrograde pathway components for cell-to-cell spread of vaccinia virus. We confirmed and extended these results while discovering that retrograde trafficking was required for virus egress rather than entry. Retro-2, a specific retrograde trafficking inhibitor of protein toxins, potently prevented spread of vaccinia virus as well as monkeypox virus, a human pathogen. Electron and confocal microscopy studies revealed that Retro-2 prevented wrapping of virions with an additional double-membrane envelope that enables microtubular transport, exocytosis, and actin polymerization. The viral B5 and F13 protein components of this membrane, which are required for wrapping, normally colocalize in the trans-Golgi network. However, only B5 traffics through the secretory pathway, suggesting that F13 uses another route to the trans-Golgi network. The retrograde route was demonstrated by finding that F13 was largely confined to early endosomes and failed to colocalize with B5 in the presence of Retro-2. Thus, vaccinia virus makes novel use of the retrograde transport system for formation of the viral wrapping membrane. Efficient cell-to-cell spread of vaccinia virus and other orthopoxviruses depends on the wrapping of infectious particles with a double membrane that enables microtubular transport, exocytosis, and actin polymerization

  1. Tritium planigraphy study of structural alterations in the coat protein of Potato virus X induced by binding of its triple gene block 1 protein to virions.

    Science.gov (United States)

    Lukashina, Elena; Badun, Gennady; Fedorova, Natalia; Ksenofontov, Alexander; Nemykh, Maria; Serebryakova, Marina; Mukhamedzhanova, Anna; Karpova, Olga; Rodionova, Nina; Baratova, Lyudmila; Dobrov, Evgeny

    2009-12-01

    Alterations in Potato virus X (PVX) coat protein structure after binding of the protein, encoded by the first gene of PVX triple gene block (triple gene block 1 protein, TGBp1), to the virions were studied using tritium planigraphy. Previously, it has been shown that TGBp1 molecules interact with the PVX particle end, containing the 5'-terminus of PVX RNA, and that this interaction results in a strong decrease in virion stability and its transformation to a translationally active state. In this work, it has been shown that the interaction of TGBp1 with PVX virions leads to an increase of approximately 50% in tritium label incorporation into the 176-198 segment of the 236-residue-long PVX coat protein subunit, with some decrease in label incorporation into the N-terminal coat protein region. According to the new 'sandwich' variant of our recently proposed model of the three-dimensional structure of the intravirus PVX coat protein, the 176-198 segment is assigned to the beta-sheet region located at the subunit surface, presumably participating in coat protein interactions with the intravirus RNA and/or in protein-protein interactions, whereas the N-terminal coat protein region corresponds to the other part of the same beta-sheet. For the remaining segments of the PVX coat protein subunit, no significant difference between tritium incorporation into untreated and TGBp1-treated PVX was observed. A detailed description of the 'sandwich' version of the intravirus PVX coat protein model is presented.

  2. Host-cell-dependent role of actin cytoskeleton during the replication of a human strain of influenza A virus.

    Science.gov (United States)

    Arcangeletti, M C; De Conto, F; Ferraglia, F; Pinardi, F; Gatti, R; Orlandini, G; Covan, S; Motta, F; Rodighiero, I; Dettori, G; Chezzi, C

    2008-01-01

    This study was aimed at investigating the possible involvement of the actin cytoskeleton in the modulation of host permissiveness to A/NWS/33 human influenza virus infection in two mammalian (MDCK and LLC-MK2) cell lines in vitro. During the early stages of infection, no appreciable association between incoming NWS/33 virions and cortical actin was detectable in the permissive MDCK model by confocal microscopy, while extensive colocalization and a slower infection progression were observed in LLC-MK2 cells. In the latter model, we also demonstrated the inability of the virus to carry out multiple replication cycles, irrespective of the presence of cleaved HA subunits in the released virions. Treatment with the actin-depolymerizing agent cytochalasin D significantly increased the infection efficiency in LLC-MK2 cells, while a detrimental effect was observed in the MDCK cell line. Our data suggest a selective role of the actin network in inducing a restriction to influenza virus replication, mostly depending on its molecular organization, the host cell type and virus replication phase.

  3. Vaccinia Virus Uses Retromer-Independent Cellular Retrograde Transport Pathways To Facilitate the Wrapping of Intracellular Mature Virions during Virus Morphogenesis

    Science.gov (United States)

    Harrison, Kate; Haga, Ismar R.; Pechenick Jowers, Tali; Jasim, Seema; Cintrat, Jean-Christophe; Gillet, Daniel; Schmitt-John, Thomas; Digard, Paul

    2016-01-01

    ABSTRACT Poxviruses, such as vaccinia virus (VACV), undertake a complex cytoplasmic replication cycle which involves morphogenesis through four distinct virion forms and includes a crucial wrapping step whereby intracellular mature virions (IMVs) are wrapped in two additional membranes to form intracellular enveloped virions (IEVs). To determine if cellular retrograde transport pathways are required for this wrapping step, we examined VACV morphogenesis in cells with reduced expression of the tetrameric tethering factor known as the GARP (Golgi-associated retrograde pathway), a central component of retrograde transport. VACV multistep replication was significantly impaired in cells transfected with small interfering RNA targeting the GARP complex and in cells with a mutated GARP complex. Detailed analysis revealed that depletion of the GARP complex resulted in a reduction in the number of IEVs, thereby linking retrograde transport with the wrapping of IMVs. In addition, foci of viral wrapping membrane proteins without an associated internal core accumulated in cells with a mutated GARP complex, suggesting that impaired retrograde transport uncouples nascent IMVs from the IEV membranes at the site of wrapping. Finally, small-molecule inhibitors of retrograde transport strongly suppressed VACV multistep growth in vitro and reduced weight loss and clinical signs in an in vivo murine model of systemic poxviral disease. This work links cellular retrograde transport pathways with the morphogenesis of poxviruses and identifies a panel of novel inhibitors of poxvirus replication. IMPORTANCE Cellular retrograde transport pathways traffic cargo from endosomes to the trans-Golgi network and are a key part of the intracellular membrane network. This work reveals that the prototypic poxvirus vaccinia virus (VACV) exploits cellular retrograde transport pathways to facilitate the wrapping of intracellular mature virions and therefore promote the production of extracellular virus

  4. Vaccinia virus uses retromer-independent cellular retrograde transport pathways to facilitate the wrapping of intracellular mature virions during viral morphogenesis.

    Science.gov (United States)

    Harrison, Kate; Haga, Ismar R; Pechenick Jowers, Tali; Jasim, Seema; Cintrat, Jean-Christophe; Gillet, Daniel; Schmitt-John, Thomas; Digard, Paul; Beard, Philippa M

    2016-08-31

    Poxviruses such as Vaccinia virus (VACV) undertake a complex cytoplasmic replication cycle which involves morphogenesis through four distinct virion forms, and includes a crucial "wrapping" step whereby intracellular mature virions (IMVs) are wrapped in two additional membranes to form intracellular enveloped virions (IEVs). To determine if cellular retrograde transport pathways were required for this wrapping step we examined VACV morphogenesis in cells with reduced expression of the tetrameric tethering factor complex GARP (Golgi-associated retrograde pathway complex), a central component of retrograde transport. VACV multi-step replication was significantly impaired in cells transfected with siRNA targeting the GARP complex or in cells with a mutated GARP complex. Detailed analysis revealed that depletion of the GARP complex resulted in a reduction in the number of IEVs, thereby linking retrograde transport with the wrapping of IMVs. In addition foci of viral wrapping membrane proteins without an associated internal core accumulated in cells with a mutated GARP complex, suggesting that impaired retrograde transport uncouples nascent IMVs from the IEV membranes at the site of wrapping. Finally, small molecule inhibitors of retrograde transport strongly suppressed VACV multi-step growth in vitro and reduced weight loss and clinical signs in an in vivo murine model of systemic poxviral disease. This work links cellular retrograde transport pathways with morphogenesis of poxviruses and identifies a panel of novel inhibitors of poxvirus replication. Cellular retrograde transport pathways traffic cargo from endosomes to the trans-Golgi network and are a key part of the intracellular membrane network. This work reveals the prototypic poxvirus Vaccinia virus (VACV) exploits cellular retrograde transport pathways to facilitate the wrapping of intracellular mature virions and therefore promote the production of extracellular virus. Inhibition of retrograde transport by

  5. Alpha interferon-induced antiretroviral activities: restriction of viral nucleic acid synthesis and progeny virion production in human immunodeficiency virus type 1-infected monocytes.

    OpenAIRE

    Baca-Regen, L; Heinzinger, N; Stevenson, M; Gendelman, H E

    1994-01-01

    Alpha interferon (IFN-alpha) restricts multiple steps of the human immunodeficiency virus type 1 (HIV-1) life cycle. A well-described effect of IFN-alpha is in the modulation of viral nucleic acid synthesis. We demonstrate that IFN-alpha influences HIV-1 DNA synthesis principally by reducing the production of late products of reverse transcription. The magnitude of IFN-alpha-induced downregulation of HIV-1 DNA and/or progeny virion production was dependent on the IFN-alpha concentration, the ...

  6. Association and host selectivity in multi-host pathogens.

    Directory of Open Access Journals (Sweden)

    José M Malpica

    2006-12-01

    Full Text Available The distribution of multi-host pathogens over their host range conditions their population dynamics and structure. Also, host co-infection by different pathogens may have important consequences for the evolution of hosts and pathogens, and host-pathogen co-evolution. Hence it is of interest to know if the distribution of pathogens over their host range is random, or if there are associations between hosts and pathogens, or between pathogens sharing a host. To analyse these issues we propose indices for the observed patterns of host infection by pathogens, and for the observed patterns of co-infection, and tests to analyse if these patterns conform to randomness or reflect associations. Applying these tests to the prevalence of five plant viruses on 21 wild plant species evidenced host-virus associations: most hosts and viruses were selective for viruses and hosts, respectively. Interestingly, the more host-selective viruses were the more prevalent ones, suggesting that host specialisation is a successful strategy for multi-host pathogens. Analyses also showed that viruses tended to associate positively in co-infected hosts. The developed indices and tests provide the tools to analyse how strong and common are these associations among different groups of pathogens, which will help to understand and model the population biology of multi-host pathogens.

  7. APOBEC3G induces a hypermutation gradient: purifying selection at multiple steps during HIV-1 replication results in levels of G-to-A mutations that are high in DNA, intermediate in cellular viral RNA, and low in virion RNA

    Directory of Open Access Journals (Sweden)

    Pathak Vinay K

    2009-02-01

    Full Text Available Abstract Background Naturally occurring Vif variants that are unable to inhibit the host restriction factor APOBEC3G (A3G have been isolated from infected individuals. A3G can potentially induce G-to-A hypermutation in these viruses, and hypermutation could contribute to genetic variation in HIV-1 populations through recombination between hypermutant and wild-type genomes. Thus, hypermutation could contribute to the generation of immune escape and drug resistant variants, but the genetic contribution of hypermutation to the viral evolutionary potential is poorly understood. In addition, the mechanisms by which these viruses persist in the host despite the presence of A3G remain unknown. Results To address these questions, we generated a replication-competent HIV-1 Vif mutant in which the A3G-binding residues of Vif, Y40RHHY44, were substituted with five alanines. As expected, the mutant was severely defective in an A3G-expressing T cell line and exhibited a significant delay in replication kinetics. Analysis of viral DNA showed the expected high level of G-to-A hypermutation; however, we found substantially reduced levels of G-to-A hypermutation in intracellular viral RNA (cRNA, and the levels of G-to-A mutations in virion RNA (vRNA were even further reduced. The frequencies of hypermutation in DNA, cRNA, and vRNA were 0.73%, 0.12%, and 0.05% of the nucleotides sequenced, indicating a gradient of hypermutation. Additionally, genomes containing start codon mutations and early termination codons within gag were isolated from the vRNA. Conclusion These results suggest that sublethal levels of hypermutation coupled with purifying selection at multiple steps during the early phase of viral replication lead to the packaging of largely unmutated genomes, providing a mechanism by which mutant Vif variants can persist in infected individuals. The persistence of genomes containing mutated gag genes despite this selection pressure indicates that dual

  8. Parasite host range and the evolution of host resistance

    NARCIS (Netherlands)

    Gorter, F.A.; Hall, A.R.; A., Buckling; P.D., Scanlan

    2015-01-01

    Parasite host range plays a pivotal role in the evolution and ecology of hosts
    and the emergence of infectious disease. Although the factors that promote
    host range and the epidemiological consequences of variation in host range
    are relatively well characterized, the effect of parasite

  9. HCMV Induces Macropinocytosis for Host Cell Entry in Fibroblasts.

    Science.gov (United States)

    Hetzenecker, Stefanie; Helenius, Ari; Krzyzaniak, Magdalena Anna

    2016-04-01

    Human cytomegalovirus (HCMV) is an important and widespread pathogen in the human population. While infection by this β-herpesvirus in endothelial, epithelial and dendritic cells depends on endocytosis, its entry into fibroblasts is thought to occur by direct fusion of the viral envelope with the plasma membrane. To characterize individual steps during entry in primary human fibroblasts, we employed quantitative assays as well as electron, fluorescence and live cell microscopy in combination with a variety of inhibitory compounds. Our results showed that while infectious entry was pH- and clathrin-independent, it required multiple, endocytosis-related factors and processes. The virions were found to undergo rapid internalization into large vacuoles containing internalized fluid and endosome markers. The characteristics of the internalization process fulfilled major criteria for macropinocytosis. Moreover, we found that soon after addition to fibroblasts the virus rapidly triggered the formation of circular dorsal ruffles in the host cell followed by the generation of large macropinocytic vacuoles. This distinctive form of macropinocytosis has been observed especially in primary cells but has not previously been reported in response to virus stimulation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. SARS Pathogenesis: Host Factors

    NARCIS (Netherlands)

    A. de Lang (Anna)

    2012-01-01

    textabstractWhile it is hypothesized that Sever Acute Respiratory Syndrome (SARS) in humans is caused by a disproportional immune response illustrated by inappropriate induction of inflammatory cytokines, the exact nature of the host response to SARS coronavirus (CoV) infection causing severe

  11. Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection

    Science.gov (United States)

    Fan, Ying; Mok, Chris Ka-Pun; Chan, Michael Chi Wai; Zhang, Yang; Nal, Béatrice; Kien, François; Bruzzone, Roberto; Sanyal, Sumana

    2017-01-01

    To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G1 phase. M2-cyclin D3 interaction was validated through GST pull-down and recapitulated in influenza A/WSN/33-infected cells. Knockdown of Ccnd3 by small interfering RNA significantly enhanced virus progeny titers in cell culture supernatants. Interestingly, the increase in virus production was due to cyclin D3 deficiency per se and not merely a consequence of cell cycle deregulation. A combined knockdown of Ccnd3 and Rb1, which rescued cell cycle progression into S phase, failed to normalize virus production. Infection by influenza A virus triggered redistribution of cyclin D3 from the nucleus to the cytoplasm, followed by its proteasomal degradation. When overexpressed in HEK 293T cells, cyclin D3 impaired binding of M2 with M1, which is essential for proper assembly of progeny virions, lending further support to its role as a putative restriction factor. Our study describes the identification and characterization of cyclin D3 as a novel interactor of influenza A virus M2 protein. We hypothesize that competitive inhibition of M1-M2 interaction by cyclin D3 impairs infectious virion formation and results in attenuated virus production. In addition, we provide mechanistic insights into the dynamic interplay of influenza virus with the host cell cycle machinery during infection. PMID:28130444

  12. A leucine residue in the C terminus of human parainfluenza virus type 3 matrix protein is essential for efficient virus-like particle and virion release.

    Science.gov (United States)

    Zhang, Guangyuan; Zhang, Shengwei; Ding, Binbin; Yang, Xiaodan; Chen, Longyun; Yan, Qin; Jiang, Yanliang; Zhong, Yi; Chen, Mingzhou

    2014-11-01

    Paramyxovirus particles, like other enveloped virus particles, are formed by budding from membranes of infected cells, and matrix (M) proteins are critical for this process. To identify the M protein important for this process, we have characterized the budding of the human parainfluenza virus type 3 (HPIV3) M protein. Our results showed that expression of the HPIV3 M protein alone is sufficient to initiate the release of virus-like particles (VLPs). Electron microscopy analysis confirmed that VLPs are morphologically similar to HPIV3 virions. We identified a leucine (L302) residue within the C terminus of the HPIV3 M protein that is critical for M protein-mediated VLP production by regulating the ubiquitination of the M protein. When L302 was mutated into A302, ubiquitination of M protein was defective, the release of VLPs was abolished, and the membrane binding and budding abilities of M protein were greatly weakened, but the ML302A mutant retained oligomerization activity and had a dominant negative effect on M protein-mediated VLP production. Furthermore, treatment with a proteasome inhibitor also inhibited M protein-mediated VLP production and viral budding. Finally, recombinant HPIV3 containing the M(L302A) mutant could not be rescued. These results suggest that L302 acts as a critical regulating signal for the ubiquitination of the HPIV3 M protein and virion release. Human parainfluenza virus type 3 (HPIV3) is an enveloped virus with a nonsegmented negative-strand RNA genome. It can cause severe respiratory tract diseases, such as bronchiolitis, pneumonia, and croup in infants and young children. However, no valid antiviral therapy or vaccine is currently available. Thus, further elucidation of its assembly and budding will be helpful in the development of novel therapeutic approaches. Here, we show that a leucine residue (L302) located at the C terminus of the HPIV3 M protein is essential for efficient production of virus-like particles (VLPs). Furthermore

  13. Characterization of exoplanet hosts

    Directory of Open Access Journals (Sweden)

    Valenti Jeff A.

    2013-04-01

    Full Text Available Spectroscopic analysis of exoplanet hosts and the stellar sample from which they are drawn provides abundances and other properties that quantitively constrain models of planet formation. The program Spectroscopy Made Easy (SME determines stellar parameters by fitting observed spectra, though line lists must be selected wisely. For giant planets, it is now well established that stars with higher metallicity are more likely to have detected companions. Stellar metallicity does not seem to affect the formation and/or migration of detectable planets less massive than Neptune, especially when considering only the most massive planet in the system. In systems with at least one planet less than 10 times the mass of Earth, the mass of the most massive planet increases dramatically with host star metallicity. This may reflect metallicity dependent timescales for core formation, envelope accretion, and/or migration into the detection zone.

  14. Hosting a Katrina Evacuee.

    Science.gov (United States)

    Hoagland, David

    2008-03-01

    No individual or institution anticipated the impact on the academic research community of hurricane Katrina. When Tulane physicist Wayne Reed asked me to host his research group just a day or two after the disaster, with no authorization or understanding of the commitment, I agreed immediately and then pondered implications. Fortunately, colleagues helped in making the commitment real, only the bureaucracy of my public university posing small hindrances. Industry was remarkably generous in providing Reed with significant ``loaner'' equipment, and amazingly, a suite of custom Reed experiments was running within weeks. At the end, the most productive collaborations for Reed seemed not to have been with my group, with its similar research, but to other groups at my institution, particularly the synthetic chemists, who gained access to methods previously unique to Tulane while offering samples previously unique to UMass. Quickly designed projects exploiting this match turned out remarkably productive. Although begun with trepidation, hosting of Reed had huge positive benefits to me and UMass, and I believe, also to Reed and Tulane. Some key lessons for the future: (i) industry has capacity and willingness to help academic research during disruption (ii) commitment of a host institution must be immediate, without a wait for formal approvals or arrangement of special funding -- delay leads only to discouragement, (iii) continuing academic progress of displaced students must come first, and (iv) intellectual synergy rather than overlap should be the basis for seeking a host. Lastly, NSF or other funding agency should consider a program directly addressing the research needs of unexpectedly disrupted academic scientists, and most particularly, graduate students who face greatly extended studies.

  15. Allergic Host Defenses

    OpenAIRE

    Palm, Noah W.; Rosenstein, Rachel K.; Medzhitov, Ruslan

    2012-01-01

    Allergies are generally thought to be a detrimental outcome of a mistargeted immune response that evolved to provide immunity to macro-parasites. Here we present arguments to suggest that allergic immunity plays an important role in host defense against noxious environmental substances, including venoms, hematophagous fluids, environmental xenobiotics and irritants. We argue that appropriately targeted allergic reactions are beneficial, although they can become detrimental when excessive. Fur...

  16. Fatty acid-producing hosts

    Science.gov (United States)

    Pfleger, Brian F; Lennen, Rebecca M

    2013-12-31

    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.

  17. Loss of the Human Cytomegalovirus US16 Protein Abrogates Virus Entry into Endothelial and Epithelial Cells by Reducing the Virion Content of the Pentamer.

    Science.gov (United States)

    Luganini, Anna; Cavaletto, Noemi; Raimondo, Stefania; Geuna, Stefano; Gribaudo, Giorgio

    2017-06-01

    The human cytomegalovirus (HCMV) US12 gene family encodes a group of predicted seven-transmembrane proteins whose functions have yet to be established. While inactivation of individual US12 members in laboratory strains of HCMV does not affect viral replication in fibroblasts, disruption of the US16 gene in the low-passage-number TR strain prevents viral growth in endothelial and epithelial cells. In these cells, the US16-null viruses fail to express immediate early (IE), early (E), and late (L) viral proteins due to a defect which occurs prior to IE gene expression. Here, we show that this defective phenotype is a direct consequence of deficiencies in the entry of US16-null viruses in these cell types due to an impact on the gH/gL/UL128/UL130/UL131A (pentamer) complex. Indeed, viral particles released from fibroblasts infected with US16-null viruses were defective for the pentamer, thus preventing entry during infections of endothelial and epithelial cells. A link between pUS16 and the pentamer was further supported by the colocalization of pUS16 and pentamer proteins within the cytoplasmic viral assembly compartment (cVAC) of infected fibroblasts. Deletion of the C-terminal tail of pUS16 reproduced the defective growth phenotype and alteration of virion composition as US16-null viruses. However, the pentamer assembly and trafficking to the cVAC were not affected by the lack of the C terminus of pUS16. Coimmunoprecipitation results then indicated that US16 interacts with pUL130 but not with the mature pentamer or gH/gL/gO. Together, these results suggest that pUS16 contributes to the tropism of HCMV by influencing the content of the pentamer into virions.IMPORTANCE Human cytomegalovirus (HCMV) is major pathogen in newborns and immunocompromised individuals. A hallmark of HCMV pathogenesis is its ability to productively replicate in an exceptionally broad range of target cells. The virus infects a variety of cell types by exploiting different forms of the envelope

  18. Potency of whole virus particle and split virion vaccines using dissolving microneedle against challenges of H1N1 and H5N1 influenza viruses in mice.

    Science.gov (United States)

    Nakatsukasa, Akihiro; Kuruma, Koji; Okamatsu, Masatoshi; Hiono, Takahiro; Suzuki, Mizuho; Matsuno, Keita; Kida, Hiroshi; Oyamada, Takayoshi; Sakoda, Yoshihiro

    2017-05-15

    Transdermal vaccination using a microneedle (MN) confers enhanced immunity compared with subcutaneous (SC) vaccination. Here we developed a novel dissolving MN patch for the influenza vaccine. The potencies of split virion and whole virus particle (WVP) vaccines prepared from A/Puerto Rico/8/1934 (H1N1) and A/duck/Hokkaido/Vac-3/2007 (H5N1), respectively, were evaluated. MN vaccination induced higher neutralizing antibody responses than SC vaccination in mice. Moreover, MN vaccination with a lower dose of antigens conferred protective immunity against lethal challenges of influenza viruses than SC vaccination in mice. These results suggest that the WVP vaccines administered using MN are an effective combination for influenza vaccine to be further validated in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Epidemiology in mixed host populations

    National Research Council Canada - National Science Library

    Garrett, K A; Mundt, C C

    1999-01-01

    ABSTRACT Although plant disease epidemiology has focused on populations in which all host plants have the same genotype, mixtures of host genotypes are more typical of natural populations and offer...

  20. Can host density attenuate parasitism?

    National Research Council Canada - National Science Library

    Magalhães, L; Freitas, R; Dairain, A; De Montaudouin, X

    .... Considering that these parasites infect cockles through filtration activity, our first hypothesis was that high host density will have a dilution effect so that infection intensity decreases with host density...

  1. Hepatitis B Virus Genotype C Isolates with Wild-Type Core Promoter Sequence Replicate Less Efficiently than Genotype B Isolates but Possess Higher Virion Secretion Capacity ▿

    Science.gov (United States)

    Qin, Yanli; Tang, Xiaoli; Garcia, Tamako; Hussain, Munira; Zhang, Jiming; Lok, Anna; Wands, Jack; Li, Jisu; Tong, Shuping

    2011-01-01

    Infection by hepatitis B virus (HBV) genotype C is associated with a prolonged viremic phase, delayed hepatitis B e antigen (HBeAg) seroconversion, and an increased incidence of liver cirrhosis and hepatocellular carcinoma compared with genotype B infection. Genotype C is also associated with the more frequent emergence of core promoter mutations, which increase genome replication and are independently associated with poor clinical outcomes. We amplified full-length HBV genomes from serum samples from Chinese and U. S. patients with chronic HBV infection and transfected circularized genome pools or dimeric constructs of individual clones into Huh7 cells. The two genotypes could be differentiated by Western blot analysis due to the reactivities of M and L proteins toward a monoclonal pre-S2 antibody and slightly different S-protein mobilities. Great variability in replication capacity was observed for both genotypes. The A1762T/G1764A core promoter mutations were prevalent in genotype C isolates and correlated with increased replication capacity, while the A1752G/T mutation frequently found in genotype B isolates correlated with a low replication capacity. Importantly, most genotype C isolates with wild-type core promoter sequence replicated less efficiently than the corresponding genotype B isolates due to less efficient transcription of the 3.5-kb RNA. However, genotype C isolates often displayed more efficient virion secretion. We propose that the low intracellular levels of viral DNA and core protein of wild-type genotype C delay immune clearance and trigger the subsequent emergence of A1762T/G1764A core promoter mutations to upregulate replication; efficient virion secretion compensates for the low replication capacity to ensure the establishment of persistent infection by genotype C. PMID:21775451

  2. 14 CFR 27.1189 - Shutoff means.

    Science.gov (United States)

    2010-01-01

    ... lines in installation using engines of less than 500 cu. in. displacement. (b) There must be means to...) There must be means to shut off each line carrying flammable fluids into the engine compartment, except— (1) Lines, fittings, and components forming an intergral part of an engine; (2) For oil systems for...

  3. Conical Seat Shut-Off Valve

    Science.gov (United States)

    Farner, Bruce

    2013-01-01

    A moveable valve for controlling flow of a pressurized working fluid was designed. This valve consists of a hollow, moveable floating piston pressed against a stationary solid seat, and can use the working fluid to seal the valve. This open/closed, novel valve is able to use metal-to-metal seats, without requiring seat sliding action; therefore there are no associated damaging effects. During use, existing standard high-pressure ball valve seats tend to become damaged during rotation of the ball. Additionally, forces acting on the ball and stem create large amounts of friction. The combination of these effects can lead to system failure. In an attempt to reduce damaging effects and seat failures, soft seats in the ball valve have been eliminated; however, the sliding action of the ball across the highly loaded seat still tends to scratch the seat, causing failure. Also, in order to operate, ball valves require the use of large actuators. Positioning the metal-to-metal seats requires more loading, which tends to increase the size of the required actuator, and can also lead to other failures in other areas such as the stem and bearing mechanisms, thus increasing cost and maintenance. This novel non-sliding seat surface valve allows metal-to-metal seats without the damaging effects that can lead to failure, and enables large seating forces without damaging the valve. Additionally, this valve design, even when used with large, high-pressure applications, does not require large conventional valve actuators and the valve stem itself is eliminated. Actuation is achieved with the use of a small, simple solenoid valve. This design also eliminates the need for many seals used with existing ball valve and globe valve designs, which commonly cause failure, too. This, coupled with the elimination of the valve stem and conventional valve actuator, improves valve reliability and seat life. Other mechanical liftoff seats have been designed; however, they have only resulted in increased cost, and incurred other reliability issues. With this novel design, the seat is lifted by simply removing the working fluid pressure that presses it against the seat and no external force is required. By eliminating variables associated with existing ball and globe configurations that can have damaging effects upon a valve, this novel design reduces downtime in rocket engine test schedules and maintenance costs.

  4. Comparing mechanisms of host manipulation across host and parasite taxa

    Science.gov (United States)

    Lafferty, Kevin D.; Shaw, Jenny C.

    2013-01-01

    Parasites affect host behavior in several ways. They can alter activity, microhabitats or both. For trophically transmitted parasites (the focus of our study), decreased activity might impair the ability of hosts to respond to final-host predators, and increased activity and altered microhabitat choice might increase contact rates between hosts and final-host predators. In an analysis of trophically transmitted parasites, more parasite groups altered activity than altered microhabitat choice. Parasites that infected vertebrates were more likely to impair the host’s reaction to predators, whereas parasites that infected invertebrates were more likely to increase the host’s contact with predators. The site of infection might affect how parasites manipulate their hosts. For instance, parasites in the central nervous system seem particularly suited to manipulating host behavior. Manipulative parasites commonly occupy the body cavity, muscles and central nervous systems of their hosts. Acanthocephalans in the data set differed from other taxa in that they occurred exclusively in the body cavity of invertebrates. In addition, they were more likely to alter microhabitat choice than activity. Parasites in the body cavity (across parasite types) were more likely to be associated with increased host contact with predators. Parasites can manipulate the host through energetic drain, but most parasites use more sophisticated means. For instance, parasites target four physiological systems that shape behavior in both invertebrates and vertebrates: neural, endocrine, neuromodulatory and immunomodulatory. The interconnections between these systems make it difficult to isolate specific mechanisms of host behavioral manipulation.

  5. The Drosophila melanogaster host model

    Science.gov (United States)

    Igboin, Christina O.; Griffen, Ann L.; Leys, Eugene J.

    2012-01-01

    The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed. PMID:22368770

  6. Host language, integration language

    Directory of Open Access Journals (Sweden)

    Maria José dos Reis Grosso

    2011-12-01

    Full Text Available With the development of language research within the Council of Europe and in a context of a stronger multilingual and multicultural Europe, we are witnessing the emergence of terms that are imposed by the frequency of their usage or that (recreate and set re-interpreted concepts according to new social and educational situations. Such is the case of the host language, a concept which is object of analysis in this paper. The relevance of the issue is preceded by other issues related to concepts like native language, second language and foreign language, already comprised in Applied Linguistics and the Teaching of Modern Languages. Nowadays, the indispensability of studying these concepts is fundamental to the pedagogic practice as well as to the language syllabus and its planning. This idea is totally supported by the proposal of the "Common European Framework of Reference for Languages: Learning, Teaching Assessment (CEFR", which provides the appropriate guidelines at the discourse level.

  7. Lettuce mosaic virus: from pathogen diversity to host interactors.

    Science.gov (United States)

    German-Retana, Sylvie; Walter, Jocelyne; Le Gall, Olivier

    2008-03-01

    Lettuce mosaic virus (LMV) belongs to the genus Potyvirus (type species Potato virus Y) in the family Potyviridae. The virion is filamentous, flexuous with a length of 750 nm and a width of 15 nm. The particles are made of a genomic RNA of 10 080 nucleotides, covalently linked to a viral-encoded protein (the VPg) at the 5' end and with a 3' poly A tail, and encapsidated in a single type of capsid protein. The molecular weight of the capsid protein subunit has been estimated electrophoretically to be 34 kDa and estimated from the amino acid sequence to be 31 kDa. The genome is expressed as a polyprotein of 3255 amino-acid residues, processed by three virus-specific proteinases into ten mature proteins. LMV has a worldwide distribution and a relatively broad host range among several families. Weeds and ornamentals can act as local reservoirs for lettuce crops. In particular, many species within the family Asteraceae are susceptible to LMV, including cultivated and ornamental species such as common (Lactuca sativa), prickly (L. serriola) or wild (L. virosa) lettuce, endive/escarole (Cichorium endiva), safflower (Carthamus tinctorius), starthistle (Centaurea solstitialis), Cape daisy (Osteospermum spp.) and gazania (Gazania rigens). In addition, several species within the families Brassicaceae, Cucurbitaceae, Fabaceae, Solanaceae and Chenopodiaceae are natural or experimental hosts of LMV. Genetic control of resistance to LMV: The only resistance genes currently used to protect lettuce crops worldwide are the recessive genes mo1(1) and mo1(2) corresponding to mutant alleles of the gene encoding the translation initiation factor eIF4E in lettuce. It is believed that at least one intact copy of eIF4E must be present to ensure virus accumulation. LMV is transmitted in a non-persistent manner by a high number of aphid species. Myzus persicae and Macrosiphum euphorbiae are particularly active in disseminating this virus in the fields. LMV is also seedborne in lettuce. The

  8. Crinivirus replication and host interactions

    Directory of Open Access Journals (Sweden)

    Zsofia A Kiss

    2013-05-01

    Full Text Available Criniviruses comprise one of the genera within the family Closteroviridae. Members in this family are restricted to the phloem and rely on whitefly vectors of the genera Bemisia and/or Trialeurodes for plant-to-plant transmission. All criniviruses have bipartite, positive-sense ssRNA genomes, although there is an unconfirmed report of one having a tripartite genome. Lettuce infectious yellows virus (LIYV is the type species of the genus, the best studied so far of the criniviruses and the first for which a reverse genetics system was available. LIYV RNA 1 encodes for proteins predicted to be involved in replication, and alone is competent for replication in protoplasts. Replication results in accumulation of cytoplasmic vesiculated membranous structures which are characteristic of most studied members of the Closteroviridae. These membranous structures, often referred to as BYV-type vesicles, are likely sites of RNA replication. LIYV RNA 2 is replicated in trans when co-infecting cells with RNA 1, but is temporally delayed relative to RNA1. Efficient RNA 2 replication also is dependent on the RNA 1-encoded RNA binding protein, P34. No LIYV RNA 2-encoded proteins have been shown to affect RNA replication, but at least four, CP, CPm, Hsp70h, and p59 are virion structural components and CPm is a determinant of whitefly transmissibility. Roles of other LIYV RNA 2-encoded proteins are largely as yet unknown, but P26 is a non-virion protein that accumulates in cells as characteristic plasmalemma deposits which in plants are localized within phloem parenchyma and companion cells over plasmodesmata connections to sieve elements. The two remaining crinivirus-conserved RNA 2-encoded proteins are P5 and P9. P5 is 39 amino acid protein and is encoded at the 5’ end of RNA 2 as ORF1 and is part of the hallmark closterovirus gene array. The orthologous gene in BYV has been shown to play a role in cell-to-cell movement and indicated to be localized to the

  9. Host-virus shift of the sphingolipid pathway along an Emiliania huxleyi bloom: survival of the fattest.

    Science.gov (United States)

    Pagarete, António; Allen, Michael J; Wilson, William H; Kimmance, Susan A; de Vargas, Colomban

    2009-11-01

    The interactions between viruses and phytoplankton play a key role in shaping the ecological and evolutionary dynamics of oceanic ecosystems. One of the most fascinating examples of horizontal gene transfer between a eukaryotic host and its virus is a de novo sphingolipid biosynthesis pathway (SBP) found in the genomes of both Emiliania huxleyi and its coccolithovirus EhV-86. Here, we focus on a natural E. huxleyi/coccolithovirus system off the coast of Norway and investigate the dynamics of host and virus homologous gene expression for two of the most important sphingolipid biosynthesis enzymes, serine palmitoyl transferase (SPT) and dihydroceramide desaturase (DCD). Transcriptional dynamics display three defined stages along E. huxleyi bloom formation and decline, with the coccolithovirus transcripts taking over and controlling the SBP in stages 2 and 3. The observed patterns fit the hypothesis according to which viral sphingolipids are involved in the timing and physical processes of virion release from the host cells. This study provides a unique insight into the transcriptional interplay of homologous metabolic pathways between virus and host during temporal progression of oceanic E. huxleyi blooms.

  10. Lytic activity of the virion-associated peptidoglycan hydrolase HydH5 of Staphylococcus aureus bacteriophage vB_SauS-phiIPLA88

    Directory of Open Access Journals (Sweden)

    Donovan David M

    2011-06-01

    Full Text Available Abstract Background Staphylococcus aureus is a food-borne pathogen and the most common cause of infections in hospitalized patients. The increase in the resistance of this pathogen to antibacterials has made necessary the development of new anti-staphylococcal agents. In this context, bacteriophage lytic enzymes such as endolysins and structural peptidoglycan (PG hydrolases have received considerable attention as possible antimicrobials against gram-positive bacteria. Results S. aureus bacteriophage vB_SauS-phiIPLA88 (phiIPLA88 contains a virion-associated muralytic enzyme (HydH5 encoded by orf58, which is located in the morphogenetic module. Comparative bioinformatic analysis revealed that HydH5 significantly resembled other peptidoglycan hydrolases encoded by staphylococcal phages. The protein consists of 634 amino acid residues. Two putative lytic domains were identified: an N-terminal CHAP (cysteine, histidine-dependent amidohydrolase/peptidase domain (135 amino acid residues, and a C-terminal LYZ2 (lysozyme subfamily 2 domain (147 amino acid residues. These domains were also found when a predicted three-dimensional structure of HydH5 was made which provided the basis for deletion analysis. The complete HydH5 protein and truncated proteins containing only each catalytic domain were overproduced in E. coli and purified from inclusion bodies by subsequent refolding. Truncated and full-length HydH5 proteins were all able to bind and lyse S. aureus Sa9 cells as shown by binding assays, zymogram analyses and CFU reduction analysis. HydH5 demonstrated high antibiotic activity against early exponential cells, at 45°C and in the absence of divalent cations (Ca2+, Mg2+, Mn2+. Thermostability assays showed that HydH5 retained 72% of its activity after 5 min at 100°C. Conclusions The virion-associated PG hydrolase HydH5 has lytic activity against S. aureus, which makes it attractive as antimicrobial for food biopreservation and anti

  11. Mistletoes as parasites: Host specificity and speciation.

    Science.gov (United States)

    Norton, D A; Carpenter, M A

    1998-03-01

    Recent research on parasite evolution has highlighted the importance of host specialization in speciation, either through host-switching or cospeciation. Many parasites show common patterns of host specificity, with higher host specificity where host abundance is high and reliable, phylogenetically conservative host specificity, and formation of races on or in different host species. Recent advances in our understanding of host specificity and speciation patterns in a variety of animal parasites provides valuable insights into the evolutionary biology of mistletoes.

  12. [Tuberculosis in compromised hosts].

    Science.gov (United States)

    2003-11-01

    Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

  13. Prototype foamy virus protease activity is essential for intraparticle reverse transcription initiation but not absolutely required for uncoating upon host cell entry.

    Science.gov (United States)

    Hütter, Sylvia; Müllers, Erik; Stanke, Nicole; Reh, Juliane; Lindemann, Dirk

    2013-03-01

    Foamy viruses (FVs) are unique among retroviruses in performing genome reverse transcription (RTr) late in replication, resulting in an infectious DNA genome, and also in their unusual Pol biosynthesis and encapsidation strategy. In addition, FVs display only very limited Gag and Pol processing by the viral protease (PR) during particle morphogenesis and disassembly, both thought to be crucial for viral infectivity. Here, we report the generation of functional prototype FV (PFV) particles from mature or partially processed viral capsid and enzymatic proteins with infectivity levels of up to 20% of the wild type. Analysis of protein and nucleic acid composition, as well as infectivity, of virions generated from different Gag and Pol combinations (including both expression-optimized and authentic PFV open reading frames [ORFs]) revealed that precursor processing of Gag, but not Pol, during particle assembly is essential for production of infectious virions. Surprisingly, when processed Gag (instead of Gag precursor) was provided together with PR-deficient Pol precursor during virus production, infectious, viral DNA-containing particles were obtained, even when different vector or proviral expression systems were used. Although virion infectivity was reduced to 0.5 to 2% relative to that of the respective parental constructs, this finding overturns the current dogma in the FV literature that viral PR activity is absolutely essential at some point during target cell entry. Furthermore, it demonstrates that viral PR-mediated Gag precursor processing during particle assembly initiates intraparticle RTr. Finally, it shows that reverse transcriptase (RT) and integrase are enzymatically active in the Pol precursor within the viral capsid, thus enabling productive host cell infection.

  14. Phytopathogenic fungus hosts a plant virus: A naturally occurring cross-kingdom viral infection.

    Science.gov (United States)

    Andika, Ida Bagus; Wei, Shuang; Cao, Chunmei; Salaipeth, Lakha; Kondo, Hideki; Sun, Liying

    2017-11-14

    The transmission of viral infections between plant and fungal hosts has been suspected to occur, based on phylogenetic and other findings, but has not been directly observed in nature. Here, we report the discovery of a natural infection of the phytopathogenic fungus Rhizoctonia solani by a plant virus, cucumber mosaic virus (CMV). The CMV-infected R. solani strain was obtained from a potato plant growing in Inner Mongolia Province of China, and CMV infection was stable when this fungal strain was cultured in the laboratory. CMV was horizontally transmitted through hyphal anastomosis but not vertically through basidiospores. By inoculation via protoplast transfection with virions, a reference isolate of CMV replicated in R. solani and another phytopathogenic fungus, suggesting that some fungi can serve as alternative hosts to CMV. Importantly, in fungal inoculation experiments under laboratory conditions, R. solani could acquire CMV from an infected plant, as well as transmit the virus to an uninfected plant. This study presents evidence of the transfer of a virus between plant and fungus, and it further expands our understanding of plant-fungus interactions and the spread of plant viruses.

  15. Three-dimensional reconstructions of the bacteriophage CUS-3 virion reveal a conserved coat protein I-domain but a distinct tailspike receptor-binding domain

    Energy Technology Data Exchange (ETDEWEB)

    Parent, Kristin N., E-mail: kparent@msu.edu [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0378 (United States); Tang, Jinghua; Cardone, Giovanni [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0378 (United States); Gilcrease, Eddie B. [University of Utah School of Medicine, Division of Microbiology and Immunology, Department of Pathology, Salt Lake City, UT 84112 (United States); Janssen, Mandy E.; Olson, Norman H. [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0378 (United States); Casjens, Sherwood R., E-mail: sherwood.casjens@path.utah.edu [University of Utah School of Medicine, Division of Microbiology and Immunology, Department of Pathology, Salt Lake City, UT 84112 (United States); Baker, Timothy S., E-mail: tsb@ucsd.edu [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0378 (United States); University of California, San Diego, Division of Biological Sciences, La Jolla, CA, 92093 (United States)

    2014-09-15

    CUS-3 is a short-tailed, dsDNA bacteriophage that infects serotype K1 Escherichia coli. We report icosahedrally averaged and asymmetric, three-dimensional, cryo-electron microscopic reconstructions of the CUS-3 virion. Its coat protein structure adopts the “HK97-fold” shared by other tailed phages and is quite similar to that in phages P22 and Sf6 despite only weak amino acid sequence similarity. In addition, these coat proteins share a unique extra external domain (“I-domain”), suggesting that the group of P22-like phages has evolved over a very long time period without acquiring a new coat protein gene from another phage group. On the other hand, the morphology of the CUS-3 tailspike differs significantly from that of P22 or Sf6, but is similar to the tailspike of phage K1F, a member of the extremely distantly related T7 group of phages. We conclude that CUS-3 obtained its tailspike gene from a distantly related phage quite recently. - Highlights: • Asymmetric and symmetric three-dimensional reconstructions of phage CUS-3 are presented. • CUS-3 major capsid protein has a conserved I-domain, which is found in all three categories of “P22-like phage”. • CUS-3 has very different tailspike receptor binding domain from those of P22 and Sf6. • The CUS-3 tailspike likely was acquired by horizontal gene transfer.

  16. Long-term immunogenicity of an inactivated split-virion 2009 pandemic influenza A H1N1 virus vaccine with or without aluminum adjuvant in mice.

    Science.gov (United States)

    Xu, Wenting; Zheng, Mei; Zhou, Feng; Chen, Ze

    2015-03-01

    In 2009, a global epidemic of influenza A(H1N1) virus caused the death of tens of thousands of people. Vaccination is the most effective means of controlling an epidemic of influenza and reducing the mortality rate. In this study, the long-term immunogenicity of influenza A/California/7/2009 (H1N1) split vaccine was observed as long as 15 months (450 days) after immunization in a mouse model. Female BALB/c mice were immunized intraperitoneally with different doses of aluminum-adjuvanted vaccine. The mice were challenged with a lethal dose (10× 50% lethal dose [LD(50)]) of homologous virus 450 days after immunization. The results showed that the supplemented aluminum adjuvant not only effectively enhanced the protective effect of the vaccine but also reduced the immunizing dose of the vaccine. In addition, the aluminum adjuvant enhanced the IgG antibody level of mice immunized with the H1N1 split vaccine. The IgG level was correlated to the survival rate of the mice. Aluminum-adjuvanted inactivated split-virion 2009 pandemic influenza A H1N1 vaccine has good immunogenicity and provided long-term protection against lethal influenza virus challenge in mice. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Elimination of contaminating cap genes in AAV vector virions reduces immune responses and improves transgene expression in a canine gene therapy model.

    Science.gov (United States)

    Wang, Z; Halbert, C L; Lee, D; Butts, T; Tapscott, S J; Storb, R; Miller, A D

    2014-04-01

    Animal and human gene therapy studies utilizing AAV vectors have shown that immune responses to AAV capsid proteins can severely limit transgene expression. The main source of capsid antigen is that associated with the AAV vectors, which can be reduced by stringent vector purification. A second source of AAV capsid proteins is that expressed from cap genes aberrantly packaged into AAV virions during vector production. This antigen source can be eliminated by the use of a cap gene that is too large to be incorporated into an AAV capsid, such as a cap gene containing a large intron (captron gene). Here, we investigated the effects of elimination of cap gene transfer and of vector purification by CsCl gradient centrifugation on AAV vector immunogenicity and expression following intramuscular injection in dogs. We found that both approaches reduced vector immunogenicity and that combining the two produced the lowest immune responses and highest transgene expression. This combined approach enabled the use of a relatively mild immunosuppressive regimen to promote robust micro-dystrophin gene expression in Duchenne muscular dystrophy-affected dogs. Our study shows the importance of minimizing AAV cap gene impurities and indicates that this improvement in AAV vector production may benefit human applications.

  18. HIV-1 Infection of T Cells and Macrophages Are Differentially Modulated by Virion-Associated Hck: A Nef-Dependent Phenomenon

    Directory of Open Access Journals (Sweden)

    Gilda Tachedjian

    2013-09-01

    Full Text Available The proline repeat motif (PxxP of Nef is required for interaction with the SH3 domains of macrophage-specific Src kinase Hck. However, the implication of this interaction for viral replication and infectivity in macrophages and T lymphocytes remains unclear. Experiments in HIV-1 infected macrophages confirmed the presence of a Nef:Hck complex which was dependent on the Nef proline repeat motif. The proline repeat motif of Nef also enhanced both HIV-1 infection and replication in macrophages, and was required for incorporation of Hck into viral particles. Unexpectedly, wild-type Hck inhibited infection of macrophages, but Hck was shown to enhance infection of primary T lymphocytes. These results indicate that the interaction between Nef and Hck is important for Nef-dependent modulation of viral infectivity. Hck-dependent enhancement of HIV-1 infection of T cells suggests that Nef-Hck interaction may contribute to the spread of HIV-1 infection from macrophages to T cells by modulating events in the producer cell, virion and target cell.

  19. Stennis hosts 2010 Special Olympics

    Science.gov (United States)

    2010-01-01

    Sarah Johnson, 28, of Gulfport, carries in the Olympic torch to signal the start of the 2010 Area III Special Olympic games at NASA's John C. Stennis Space Center on March 27. Stennis volunteers hosted special needs athletes from across the area for the event. Stennis is an annual host of the games.

  20. Larval helminths in intermediate hosts

    DEFF Research Database (Denmark)

    Fredensborg, Brian Lund; Poulin, R

    2005-01-01

    Density-dependent effects on parasite fitness have been documented from adult helminths in their definitive hosts. There have, however, been no studies on the cost of sharing an intermediate host with other parasites in terms of reduced adult parasite fecundity. Even if larval parasites suffer...... a reduction in size, caused by crowding, virtually nothing is known about longer-lasting effects after transmission to the definitive host. This study is the first to use in vitro cultivation with feeding of adult trematodes to investigate how numbers of parasites in the intermediate host affect the size...... and fecundity of adult parasites. For this purpose, we examined two different infracommunities of parasites in crustacean hosts. Firstly, we used experimental infections of Maritrema novaezealandensis in the amphipod, Paracalliope novizealandiae, to investigate potential density-dependent effects in single...

  1. Surface-exposed adeno-associated virus Vp1-NLS capsid fusion protein rescues infectivity of noninfectious wild-type Vp2/Vp3 and Vp3-only capsids but not that of fivefold pore mutant virions.

    Science.gov (United States)

    Grieger, Joshua C; Johnson, Jarrod S; Gurda-Whitaker, Brittney; Agbandje-McKenna, Mavis; Samulski, R Jude

    2007-08-01

    Over the past 2 decades, significant effort has been dedicated to the development of adeno-associated virus (AAV) as a vector for human gene therapy. However, understanding of the virus with respect to the functional domains of the capsid remains incomplete. In this study, the goal was to further examine the role of the unique Vp1 N terminus, the N terminus plus the recently identified nuclear localization signal (NLS) (J. C. Grieger, S. Snowdy, and R. J. Samulski, J. Virol 80:5199-5210, 2006), and the virion pore at the fivefold axis in infection. We generated two Vp1 fusion proteins (Vp1 and Vp1NLS) linked to the 8-kDa chemokine domain of rat fractalkine (FKN) for the purpose of surface exposure upon assembly of the virion, as previously described (K. H. Warrington, Jr., O. S. Gorbatyuk, J. K. Harrison, S. R. Opie, S. Zolotukhin, and N. Muzyczka, J. Virol 78:6595-6609, 2004). The unique Vp1 N termini were found to be exposed on the surfaces of these capsids and maintained their phospholipase A2 (PLA2) activity, as determined by native dot blot Western and PLA2 assays, respectively. Incorporation of the fusions into AAV type 2 capsids lacking a wild-type Vp1, i.e., Vp2/Vp3 and Vp3 capsid only, increased infectivity by 3- to 5-fold (Vp1FKN) and 10- to 100-fold (Vp1NLSFKN), respectively. However, the surface-exposed fusions did not restore infectivity to AAV virions containing mutations at a conserved leucine (Leu336Ala, Leu336Cys, or Leu336Trp) located at the base of the fivefold pore. EM analyses suggest that Leu336 may play a role in global structural changes to the virion directly impacting downstream conformational changes essential for infectivity and not only have local effects within the pore, as previously suggested.

  2. Essential role of the unordered VP2 n-terminal domain of the parvovirus MVM capsid in nuclear assembly and endosomal enlargement of the virion fivefold channel for cell entry

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Martinez, Cristina; Grueso, Esther [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Universidad Autonoma de Madrid, 28049 Cantoblanco, Madrid (Spain); Carroll, Miles [Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury SP4 OJG, Wilts (United Kingdom); Rommelaere, Jean [Deutsches Krebsforschungszentrum Division F010, Im Neuenheimer Feld 242, D-69120 Heidelberg (Germany); Almendral, Jose M., E-mail: jmalmendral@cbm.uam.es [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Universidad Autonoma de Madrid, 28049 Cantoblanco, Madrid (Spain)

    2012-10-10

    The unordered N-termini of parvovirus capsid proteins (Nt) are translocated through a channel at the icosahedral five-fold axis to serve for virus traffick. Heterologous peptides were genetically inserted at the Nt of MVM to study their functional tolerance to manipulations. Insertion of a 5T4-single-chain antibody at VP2-Nt (2Nt) yielded chimeric capsid subunits failing to enter the nucleus. The VEGFR2-binding peptide (V1) inserted at both 2Nt and VP1-Nt efficiently assembled in virions, but V1 disrupted VP1 and VP2 entry functions. The VP2 defect correlated with restricted externalization of V1-2Nt out of the coat. The specific infectivity of MVM and wtVP-pseudotyped mosaic MVM-V1 virions, upon heating and/or partial 2Nt cleavage, demonstrated that some 2Nt domains become intracellularly translocated out of the virus shell and cleaved to initiate entry. The V1 insertion defines a VP2-driven endosomal enlargement of the channel as an essential structural rearrangement performed by the MVM virion to infect.

  3. Towards host-to-host meeting scheduling negotiation

    Directory of Open Access Journals (Sweden)

    Rani Megasari

    2015-03-01

    Full Text Available This paper presents a different scheme of meeting scheduling negotiation among a large number of personnel in a heterogeneous community. This scheme, named Host-to-Host Negotiation, attempts to produce a stable schedule under uncertain personnel preferences. By collecting information from hosts’ inter organizational meeting, this study intends to guarantee personnel availability. As a consequence, personnel’s and meeting’s profile in this scheme are stored in a centralized manner. This study considers personnel preferences by adapting the Clarke Tax Mechanism, which is categorized as a non manipulated mechanism design. Finally, this paper introduces negotiation strategies based on the conflict handling mode. A host-to-host scheme can give notification if any conflict exist and lead to negotiation process with acceptable disclosed information. Nevertheless, a complete negotiation process will be more elaborated in the future works.

  4. Shigella hacks host immune responses by reprogramming the host epigenome.

    Science.gov (United States)

    Ashida, Hiroshi; Sasakawa, Chihiro

    2014-11-18

    Bacterial pathogens alter host transcriptional programs to promote infection. Shigella OspF is an essential virulence protein with a unique phosphothreonine lyase activity. A new study in The EMBO Journal (Harouz et al, 2014) reveals a novel function of OspF: targeting of heterochromatin protein 1γ (HP1γ) and downregulation of a subset of immune genes. These results illustrate how bacterial pathogens exploit epigenetic modifications to counteract host immune responses.

  5. Use of a novel cell-based fusion reporter assay to explore the host range of human respiratory syncytial virus F protein

    Directory of Open Access Journals (Sweden)

    Sarisky Robert T

    2005-07-01

    Full Text Available Abstract Human respiratory syncytial virus (HRSV is an important respiratory pathogen primarily affecting infants, young children, transplant recipients and the elderly. The F protein is the only virion envelope protein necessary and sufficient for virus replication and fusion of the viral envelope membrane with the target host cell. During natural infection, HRSV replication is limited to respiratory epithelial cells with disseminated infection rarely, if ever, occurring even in immunocompromised patients. However, in vitro infection of multiple human and non-human cell types other than those of pulmonary tract origin has been reported. To better define host cell surface molecules that mediate viral entry and dissect the factors controlling permissivity for HRSV, we explored the host range of HRSV F protein mediated fusion. Using a novel recombinant reporter gene based fusion assay, HRSV F protein was shown to mediate fusion with cells derived from a wide range of vertebrate species including human, feline, equine, canine, bat, rodent, avian, porcine and even amphibian (Xenopus. That finding was extended using a recombinant HRSV engineered to express green fluorescent protein (GFP, to confirm that viral mRNA expression is limited in several cell types. These findings suggest that HRSV F protein interacts with either highly conserved host cell surface molecules or can use multiple mechanisms to enter cells, and that the primary determinants of HRSV host range are at steps post-entry.

  6. Mistletoe ecophysiology: Host-parasite interactions

    Science.gov (United States)

    G. Glatzel; B. W. Geils

    2009-01-01

    Mistletoes are highly specialized perennial flowering plants adapted to parasitic life on aerial parts of their hosts. In our discussion on the physiological interactions between parasite and host, we focus on water relations, mineral nutrition, and the effect of host vigour. When host photosynthesis is greatest, the xylem water potential of the host is most negative....

  7. Improved Prefusion Stability, Optimized Codon Usage, and Augmented Virion Packaging Enhance the Immunogenicity of Respiratory Syncytial Virus Fusion Protein in a Vectored-Vaccine Candidate.

    Science.gov (United States)

    Liang, Bo; Ngwuta, Joan O; Surman, Sonja; Kabatova, Barbora; Liu, Xiang; Lingemann, Matthias; Liu, Xueqiao; Yang, Lijuan; Herbert, Richard; Swerczek, Joanna; Chen, Man; Moin, Syed M; Kumar, Azad; McLellan, Jason S; Kwong, Peter D; Graham, Barney S; Collins, Peter L; Munir, Shirin

    2017-08-01

    Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but it lacks a licensed vaccine or suitable antiviral drug. A live attenuated chimeric bovine/human parainfluenza virus type 3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naive children, rB/HPIV3 was well tolerated but the immunogenicity of wild-type RSV F was unsatisfactory. We previously modified RSV F with a designed disulfide bond (DS) to increase stability in the prefusion (pre-F) conformation and to be efficiently packaged in the vector virion. Here, we further stabilized pre-F by adding both disulfide and cavity-filling mutations (DS-Cav1), and we also modified RSV F codon usage to have a lower CpG content and a higher level of expression. This RSV F open reading frame was evaluated in rB/HPIV3 in three forms: (i) pre-F without vector-packaging signal, (ii) pre-F with vector-packaging signal, and (iii) secreted pre-F ectodomain trimer. Despite being efficiently expressed, the secreted pre-F was poorly immunogenic. DS-Cav1 stabilized pre-F, with or without packaging, induced higher titers of pre-F specific antibodies in hamsters, and improved the quality of RSV-neutralizing serum antibodies. Codon-optimized RSV F containing fewer CpG dinucleotides had higher F expression, replicated more efficiently in vivo, and was more immunogenic. The combination of DS-Cav1 pre-F stabilization, optimized codon usage, reduced CpG content, and vector packaging significantly improved vector immunogenicity and protective efficacy against RSV. This provides an improved vectored RSV vaccine candidate suitable for pediatric clinical evaluation.IMPORTANCE RSV and HPIV3 are the first and second leading viral causes of severe pediatric respiratory disease worldwide. Licensed vaccines or suitable antiviral drugs are not available. We

  8. The African Swine Fever Virus Virion Membrane Protein pE248R Is Required for Virus Infectivity and an Early Postentry Event ▿

    Science.gov (United States)

    Rodríguez, Irene; Nogal, María L.; Redrejo-Rodríguez, Modesto; Bustos, María J.; Salas, María L.

    2009-01-01

    The African swine fever virus (ASFV) protein pE248R, encoded by the gene E248R, is a late structural component of the virus particle. The protein contains intramolecular disulfide bonds and has been previously identified as a substrate of the ASFV-encoded redox system. Its amino acid sequence contains a putative myristoylation site and a hydrophobic transmembrane region near its carboxy terminus. We show here that the protein pE248R is myristoylated during infection and associates with the membrane fraction in infected cells, behaving as an integral membrane protein. Furthermore, the protein localizes at the inner envelope of the virus particles in the cytoplasmic factories. The function of the protein pE248R in ASFV replication was investigated by using a recombinant virus that inducibly expresses the gene E248R. Under repressive conditions, the ASFV polyproteins pp220 and pp62 are normally processed and virus particles with morphology indistinguishable from that of those produced in a wild-type infection or under permissive conditions are generated. Moreover, the mutant virus particles can exit the cell as does the parental virus. However, the infectivity of the pE248R-deficient virions was reduced at least 100-fold. An investigation of the defect of the mutant virus indicated that neither virus binding nor internalization was affected by the absence of the protein pE248R, but a cytopathic effect was not induced and early and late gene expression was impaired, indicating that the protein is required for some early postentry event. PMID:19793823

  9. The African swine fever virus virion membrane protein pE248R is required for virus infectivity and an early postentry event.

    Science.gov (United States)

    Rodríguez, Irene; Nogal, María L; Redrejo-Rodríguez, Modesto; Bustos, María J; Salas, María L

    2009-12-01

    The African swine fever virus (ASFV) protein pE248R, encoded by the gene E248R, is a late structural component of the virus particle. The protein contains intramolecular disulfide bonds and has been previously identified as a substrate of the ASFV-encoded redox system. Its amino acid sequence contains a putative myristoylation site and a hydrophobic transmembrane region near its carboxy terminus. We show here that the protein pE248R is myristoylated during infection and associates with the membrane fraction in infected cells, behaving as an integral membrane protein. Furthermore, the protein localizes at the inner envelope of the virus particles in the cytoplasmic factories. The function of the protein pE248R in ASFV replication was investigated by using a recombinant virus that inducibly expresses the gene E248R. Under repressive conditions, the ASFV polyproteins pp220 and pp62 are normally processed and virus particles with morphology indistinguishable from that of those produced in a wild-type infection or under permissive conditions are generated. Moreover, the mutant virus particles can exit the cell as does the parental virus. However, the infectivity of the pE248R-deficient virions was reduced at least 100-fold. An investigation of the defect of the mutant virus indicated that neither virus binding nor internalization was affected by the absence of the protein pE248R, but a cytopathic effect was not induced and early and late gene expression was impaired, indicating that the protein is required for some early postentry event.

  10. Varicella-zoster virus glycoprotein I is essential for spread in dorsal root ganglia and facilitates axonal localization of structural virion components in neuronal cultures.

    Science.gov (United States)

    Christensen, Jenna; Steain, Megan; Slobedman, Barry; Abendroth, Allison

    2013-12-01

    Neurons of the sensory ganglia are the major site of varicella-zoster virus (VZV) latency and may undergo productive infection during reactivation. Although the VZV glycoprotein E/glycoprotein I (gE/gI) complex is known to be critical for neurovirulence, few studies have assessed the roles of these proteins during infection of dorsal root ganglia (DRG) due to the high human specificity of the virus. Here, we show that the VZV glycoprotein I gene is an important neurotropic gene responsible for mediating the spread of virus in neuronal cultures and explanted DRG. Inoculation of differentiated SH-SY5Y neuronal cell cultures with a VZV gI gene deletion strain (VZV rOkaΔgI) showed a large reduction in the percentage of cells infected and significantly smaller plaque sizes in a comparison with cultures infected with the parental strain (VZV rOka). In contrast, VZV rOkaΔgI was not significantly attenuated in fibroblast cultures, demonstrating a cell type-specific role for VZV gI. Analysis of rOkaΔgI protein localization by immunofluorescent staining revealed aberrant localization of viral glycoprotein and capsid proteins, with little or no staining present in the axons of differentiated SH-SY5Y cells infected with rOkaΔgI, yet axonal vesicle trafficking was not impaired. Further studies utilizing explanted human DRG indicated that VZV gI is required for the spread of virus within DRG. These data demonstrate a role for VZV gI in the cell-to-cell spread of virus during productive replication in neuronal cells and a role in facilitating the access of virion components to axons.

  11. Amphipathic alpha-helices and putative cholesterol binding domains of the influenza virus matrix M1 protein are crucial for virion structure organisation.

    Science.gov (United States)

    Tsfasman, Tatyana; Kost, Vladimir; Markushin, Stanislav; Lotte, Vera; Koptiaeva, Irina; Bogacheva, Elena; Baratova, Ludmila; Radyukhin, Victor

    2015-12-02

    The influenza virus matrix M1 protein is an amphitropic membrane-associated protein, forming the matrix layer immediately beneath the virus raft membrane, thereby ensuring the proper structure of the influenza virion. The objective of this study was to elucidate M1 fine structural characteristics, which determine amphitropic properties and raft membrane activities of the protein, via 3D in silico modelling with subsequent mutational analysis. Computer simulations suggest the amphipathic nature of the M1 α-helices and the existence of putative cholesterol binding (CRAC) motifs on six amphipathic α-helices. Our finding explains for the first time many features of this protein, particularly the amphitropic properties and raft/cholesterol binding potential. To verify these results, we generated mutants of the A/WSN/33 strain via reverse genetics. The M1 mutations included F32Y in the CRAC of α-helix 2, W45Y and W45F in the CRAC of α-helix 3, Y100S in the CRAC of α-helix 6, M128A and M128S in the CRAC of α-helix 8 and a double L103I/L130I mutation in both a putative cholesterol consensus motif and the nuclear localisation signal. All mutations resulted in viruses with unusual filamentous morphology. Previous experimental data regarding the morphology of M1-gene mutant influenza viruses can now be explained in structural terms and are consistent with the pivotal role of the CRAC-domains and amphipathic α-helices in M1-lipid interactions. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Cellular host responses to gliomas.

    Directory of Open Access Journals (Sweden)

    Joseph Najbauer

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. METHODOLOGY/PRINCIPAL FINDINGS: Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a 'network' with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a 'pair-wise' manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a low-generation tumors (first in vivo passage in rats were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b high-generation xenografts (fifth passage had pronounced cellularity, were angiogenic with 'glomerulus-like' microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  13. HostPhinder: A Phage Host Prediction Tool

    DEFF Research Database (Denmark)

    Villarroel, Julia; Kleinheinz, Kortine Annina; Jurtz, Vanessa Isabell

    2016-01-01

    and significantly outperforming BLAST on phages for which both had predictions. HostPhinder predictions on phage draft genomes from the INTESTI phage cocktail corresponded well with the advertised targets of the cocktail. Our study indicates that for most phages genomic similarity correlates well with related...

  14. Host-pathogen interactions in Campylobacter infections: the host perspective

    NARCIS (Netherlands)

    Janssen, R.; Krogfelt, K.A.; Cawthraw, S.A.; Pelt, van W.; Wagenaar, J.A.; Owen, R.J.

    2008-01-01

    Campylobacter is a major cause of acute bacterial diarrhea in humans worldwide. This study was aimed at summarizing the current understanding of host mechanisms involved in the defense against Campylobacter by evaluating data available from three sources: (i) epidemiological observations, (ii)

  15. The Inflammasome in Host Defense

    Directory of Open Access Journals (Sweden)

    Gang Chen

    2009-12-01

    Full Text Available Nod-like receptors have emerged as an important family of sensors in host defense. These receptors are expressed in macrophages, dendritic cells and monocytes and play an important role in microbial immunity. Some Nod-like receptors form the inflammasome, a protein complex that activates caspase-1 in response to several stimuli. Caspase-1 activation leads to processing and secretion of pro-inflammatory cytokines such as interleukin (IL-1β and IL-18. Here, we discuss recent advances in the inflammasome field with an emphasis on host defense. We also compare differential requirements for inflammasome activation in dendritic cells, macrophages and monocytes.

  16. The Effect of Hydrogen Sulfide Concentration on Gel as Water Shutoff Agent Effet de la concentration en sulfure d'hydrogène sur un gel utilisé en tant qu'agent de traitement des venues d'eaux

    Directory of Open Access Journals (Sweden)

    You Q.

    2011-11-01

    Full Text Available For drilling and water shutoff of oil and gas reservoirs containing hydrogen sulfide (H2S, the effects of H2S on widely used gel as water shutoff agents are studied. The gels include Na2Cr2O7/Na2SO3/HPAM gel, Na2Cr2O7/(NH22CS/HPAM gel, Cr(III-acetate & Cr(III-lactate/HPAM gel and phenol formaldehyde resin/HPAM gel. The results show that: for Na2Cr2O7/Na2SO3/HPAM gel and Na2Cr2O7/(NH22CS/HPAM gel, the H2S as reducing agent (the reducibility is more efficient than that of Na2SO3and (NH22CS can reduce Cr(VI into Cr(III and accelerate crosslinking reaction with HPAM in low concentration of H2S, while it can react with Cr(III generating Cr2S3 precipitation in high concentration of H2S, for which the bulk gel can not form without Cr(III; for Cr(III-acetate & Cr(III-lactate/HPAM gel, H2S can prolong the gelation time and reduce the gel strength by decreasing pH value; for phenol formaldehyde resin/HPAM gel, H2S can slightly prolong the gelation time and slightly reduce the gel strength by decreasing pH value. Therefore, according to the comprehensive investigations of the effects of H2S on gel as water shutoff agents, the phenol formaldehyde resin/HPAM gel is recommended as the water shutoff agents suitable for oil and gas reservoir containing H2S. Pour le forage et le traitement des venues d’eau dans des réservoirs d’huile et de gaz contenant du sulfure d’hydrogène (H2S, les effets de l’H2S sur les gels couramment utilisés pour le traitement des venues d’eau sont étudiés. Les gels incluent un gel de Na2Cr2O7/Na2SO3/HPAM, un gel de Na2Cr2O7/(NH22CS/HPAM, un gel d’acétate de Cr(III & lactate de Cr(III/HPAM et un gel à base de résine de phénol formaldéhyde/HPAM. Les résultats montrent que : pour un gel de Na2Cr2O7/Na2SO3/HPAM et un gel de Na2Cr2O7/(NH22CS/HPAM, l’H2S en tant qu’agent réducteur (la réductibilité est plus efficace que celle du Na2SO3et du (NH22CS peut réduire le Cr(VI en Cr(III et accélérer la réaction de

  17. Olfaction in vector-host interactions

    NARCIS (Netherlands)

    Takken, W.; Knols, B.G.J.

    2010-01-01

    This book addresses the topic how blood-feeding arthropods interact with their vertebrate hosts. As the transmission of infectious vector-borne pathogens is much dependent on the contact between vector and host, the efficacy of host location is of profound importance. Interruption of vector-host

  18. Chemical signaling in mosquito–host interactions

    NARCIS (Netherlands)

    Takken, Willem; Verhulst, Niels O.

    2017-01-01

    Anthropophilic mosquitoes use host-derived volatile compounds for host seeking. Recently it has become evident that many of these compounds are of microbial origin. Host seeking of mosquitoes is, therefore, a tritrophic relationship and suggests co-evolution between blood hosts and their

  19. An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses.

    Science.gov (United States)

    Holthausen, David J; Lee, Song Hee; Kumar, Vineeth Tv; Bouvier, Nicole M; Krammer, Florian; Ellebedy, Ali H; Wrammert, Jens; Lowen, Anice C; George, Sanil; Pillai, Madhavan Radhakrishna; Jacob, Joshy

    2017-04-18

    Although vaccines confer protection against influenza A viruses, antiviral treatment becomes the first line of defense during pandemics because there is insufficient time to produce vaccines. Current antiviral drugs are susceptible to drug resistance, and developing new antivirals is essential. We studied host defense peptides from the skin of the South Indian frog and demonstrated that one of these, which we named "urumin," is virucidal for H1 hemagglutinin-bearing human influenza A viruses. This peptide specifically targeted the conserved stalk region of H1 hemagglutinin and was effective against drug-resistant H1 influenza viruses. Using electron microscopy, we showed that this peptide physically destroyed influenza virions. It also protected naive mice from lethal influenza infection. Urumin represents a unique class of anti-influenza virucide that specifically targets the hemagglutinin stalk region, similar to targeting of antibodies induced by universal influenza vaccines. Urumin therefore has the potential to contribute to first-line anti-viral treatments during influenza outbreaks. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Fungal transcriptomics from host samples

    Directory of Open Access Journals (Sweden)

    Sara eAmorim-Vaz

    2016-01-01

    Full Text Available Candida albicans adaptation to the host requires a profound reprogramming of the fungal transcriptome as compared to in vitro laboratory conditions. A detailed knowledge of the C. albicans transcriptome during the infection process is necessary in order to understand which of the fungal genes are important for host adaptation. Such genes could be thought of as potential targets for antifungal therapy. The acquisition of the C. albicans transcriptome is however technically challenging due to the low proportion of fungal RNA in host tissues. Two emerging technologies were used recently to circumvent this problem. One consists of the detection of low abundance fungal RNA using capture and reporter gene probes which is followed by emission and quantification of resulting fluorescent signals (nanoString. The other is based first on the capture of fungal RNA by short biotinylated oligonucleotide baits covering the C. albicans ORFome permitting fungal RNA purification. Next, the enriched fungal RNA is amplified and subjected RNA sequencing (RNA-seq. Here we detail these two transcriptome approaches and discuss their advantages and limitations and future perspectives in microbial transcriptomics from host material.

  1. Biosignatures of Pathogen and Host

    Energy Technology Data Exchange (ETDEWEB)

    Fitch, J P; Chromy, B A; Forde, C E; Garcia, E; Gardner, S N; Gu, P P; Kuczmarksi, T A; Melius, C F; McCutchen-Maloney, S L; Milanovich, F P; Motin, V L; Ott, L L; Quong, A A; Quong, J N; Rocco, J M; Slezak, T R; Sokhansanj, B A; Vitalis, E A; Zemla, A T; McCready, P M

    2002-08-27

    In information theory, a signature is characterized by the information content as well as noise statistics of the communication channel. Biosignatures have analogous properties. A biosignature can be associated with a particular attribute of a pathogen or a host. However, the signature may be lost in backgrounds of similar or even identical signals from other sources. In this paper, we highlight statistical and signal processing challenges associated with identifying good biosignatures for pathogens in host and other environments. In some cases it may be possible to identify useful signatures of pathogens through indirect but amplified signals from the host. Discovery of these signatures requires new approaches to modeling and data interpretation. For environmental biosignal collections, it is possible to use signal processing techniques from other applications (e.g., synthetic aperture radar) to track the natural progression of microbes over large areas. We also present a computer-assisted approach to identify unique nucleic-acid based microbial signatures. Finally, an understanding of host-pathogen interactions will result in better detectors as well as opportunities in vaccines and therapeutics.

  2. Host Event Based Network Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Jonathan Chugg

    2013-01-01

    The purpose of INL’s research on this project is to demonstrate the feasibility of a host event based network monitoring tool and the effects on host performance. Current host based network monitoring tools work on polling which can miss activity if it occurs between polls. Instead of polling, a tool could be developed that makes use of event APIs in the operating system to receive asynchronous notifications of network activity. Analysis and logging of these events will allow the tool to construct the complete real-time and historical network configuration of the host while the tool is running. This research focused on three major operating systems commonly used by SCADA systems: Linux, WindowsXP, and Windows7. Windows 7 offers two paths that have minimal impact on the system and should be seriously considered. First is the new Windows Event Logging API, and, second, Windows 7 offers the ALE API within WFP. Any future work should focus on these methods.

  3. Host-Pathogen Coupled Interactions

    Science.gov (United States)

    2015-01-04

    REPORT TYPE Interim 3. DATES COVERED (From - To) Oct 2012 – Oct. 2014 4. TITLE AND SUBTITLE Host-Pathogen Coupled Interactions 5a. CONTRACT NUMBER...Similarly, Bacillus anthracis (BA) produces lethal factor (LF) that also accumulates in the cytosol of macrophages, cleaving the MAPKKs and leading to

  4. Host Defence to Pulmonary Mycosis

    Directory of Open Access Journals (Sweden)

    Christopher H Mody

    1999-01-01

    Full Text Available OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease.

  5. Adaptation of bacteriophages to new hosts through overcoming the interspecific barrier

    Directory of Open Access Journals (Sweden)

    Е. N. Andriychuk

    2016-10-01

    Full Text Available Four wild type phage isolates were tested on P. syringae isolated from potato tuber samples collected in the Kiev and Cherkasy regions of Ukraine. The isolated phages formed clear plaques and had a virion size of 2 to 12 nm. Electron microscopy showed that the phages were of similar size and structure and consisted of isometric particles with long tails characteristic of the Podoviridae family. The effectiveness of phage culturing on bacteria different from the original host was also studied on two phytopathogenic strains of Pseudomonas savastanoi pv. рhaseolicola 4013 and P. syringae pv. tabaci 223. However, no stable isolates could be extracted from P. savastanoi pv. phaseolicola as the plages became inactive after a few passages on the bacterial culture. In order to overcome this, the phages were first cultured on P. syringae pv. tabaci before being transferred to P. savastanoi pv. рhaseolicola. The titers obtained were compared with phage titers from the original host bacteria. Thus, it was determined that the changes occuring in phages after their transfer to the Pseudomonas strain 4013 were irreversible. The changes were evaluated by comparing the effectiveness of phage culturing after a cycle of passages on strains 4013 and 223 where the phages were adapted to strain 4013 after being cultured on strain 223. Additionally, the effectiveness of phage culturing on strain 223 was also determined. The change in the effectiveness of phage culturing for the entire phage range suggests the presence of a defensive system in bacteria when the phages were transferred from strain 223 to strain 4013. The irreversibility of the changes occuring in phages was also tested and it was determined that phages 223/4 and 7591/2 adapt to original hosts and swiftly restore their original titers. Phage 7591/1, however, showed titers that were lower than the ones obtained from the original host culture. The testing of the irreversibility of changes in phages

  6. Specificity of Baculorivus P6.9 Basic DNA-Binding Proteins and Critical Role of the C Terminus in Virion Formation

    NARCIS (Netherlands)

    Wang, M.; Tuladhar, E.; Shen, S.; Wang, H.; Oers, van M.M.; Vlak, J.M.; Westenberg, M.

    2010-01-01

    The majority of double-stranded DNA (dsDNA) viruses infecting eukaryotic organisms use host- or virus-expressed histones or protamine-like proteins to condense their genomes. In contrast, members of the Baculoviridae family use a protamine-like protein named P6.9. The dephosphorylated form of P6.9

  7. The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does not influence packaging of a functional RNA genome

    NARCIS (Netherlands)

    van Bel, Nikki; van der Velden, Yme; Bonnard, Damien; Le Rouzic, Erwann; Das, Atze T.; Benarous, Richard; Berkhout, Ben

    2014-01-01

    The viral integrase (IN) is an essential protein for HIV-1 replication. IN inserts the viral dsDNA into the host chromosome, thereby aided by the cellular co-factor LEDGF/p75. Recently a new class of integrase inhibitors was described: allosteric IN inhibitors (ALLINIs). Although designed to

  8. Reducing uncertainty in within-host parameter estimates of influenza infection by measuring both infectious and total viral load.

    Directory of Open Access Journals (Sweden)

    Stephen M Petrie

    Full Text Available For in vivo studies of influenza dynamics where within-host measurements are fit with a mathematical model, infectivity assays (e.g. 50% tissue culture infectious dose; TCID50 are often used to estimate the infectious virion concentration over time. Less frequently, measurements of the total (infectious and non-infectious viral particle concentration (obtained using real-time reverse transcription-polymerase chain reaction; rRT-PCR have been used as an alternative to infectivity assays. We investigated the degree to which measuring both infectious (via TCID50 and total (via rRT-PCR viral load allows within-host model parameters to be estimated with greater consistency and reduced uncertainty, compared with fitting to TCID50 data alone. We applied our models to viral load data from an experimental ferret infection study. Best-fit parameter estimates for the "dual-measurement" model are similar to those from the TCID50-only model, with greater consistency in best-fit estimates across different experiments, as well as reduced uncertainty in some parameter estimates. Our results also highlight how variation in TCID50 assay sensitivity and calibration may hinder model interpretation, as some parameter estimates systematically vary with known uncontrolled variations in the assay. Our techniques may aid in drawing stronger quantitative inferences from in vivo studies of influenza virus dynamics.

  9. Vaccinia virus A43R gene encodes an orthopoxvirus-specific late non-virion type-1 membrane protein that is dispensable for replication but enhances intradermal lesion formation.

    Science.gov (United States)

    Sood, Cindy L; Moss, Bernard

    2010-01-05

    The vaccinia virus A43R open reading frame encodes a 168-amino acid protein with a predicted N-terminal signal sequence and a C-terminal transmembrane domain. Although A43R is conserved in all sequenced members of the orthopoxvirus genus, no non-orthopoxvirus homolog or functional motif was recognized. Biochemical and confocal microscopic studies indicated that A43 is expressed at late times following viral DNA synthesis and is a type-1 membrane protein with two N-linked oligosaccharide chains. A43 was present in Golgi and plasma membranes but only a trace amount was detected in sucrose gradient purified mature virions and none in CsCl gradient purified enveloped virions. Prevention of A43R expression had no effect on plaque size or virus replication in cell culture and little effect on virulence after mouse intranasal infection. Although the A43 mutant produced significantly smaller lesions in skin of mice than the control, the amounts of virus recovered from the lesions were similar.

  10. Host modulation by therapeutic agents

    Directory of Open Access Journals (Sweden)

    Sugumari Elavarasu

    2012-01-01

    Full Text Available Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs, bisphosphonates, nitrous oxide (NO synthase inhibitors, recombinant human interleukin-11 (rhIL-11, omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA, mitogen-activated protein kinase (MAPK inhibitors, nuclear factor-kappa B (NF-kb inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α are some of the therapeutic agents that have host modulation properties.

  11. A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice

    OpenAIRE

    Ogembo, Javier Gordon; Muraswki, Matthew R; McGinnes, Lori W.; Parcharidou, Agapi; Sutiwisesak, Rujapak; Tison, Timelia; Avendano, Juan; Agnani, Deep; Finberg, Robert W.; Morrison, Trudy G.; Fingeroth, Joyce D.

    2015-01-01

    Epstein-Barr virus (EBV), an oncogenic gammaherpesvirus, causes acute infectious mononucleosis (AIM) and is linked to the development of several human malignancies. There is an urgent need for a vaccine that is safe, prevents infection and/or limits disease. Unique among human herpesviruses, glycoprotein (gp)350/220, which initiates EBV attachment to susceptible host cells, is the major ligand on the EBV envelope and is highly conserved. Interaction between gp350/220 and complement receptor t...

  12. PERCEPTION OF HOST COMMUNITIES TOWARD THE ...

    African Journals Online (AJOL)

    DORCAS

    PERCEPTION OF HOST COMMUNITIES TOWARD THE IMPLEMENTATION OF. PARK LAWS IN OKOMU NATIONAL ... Keywords; Perception, Host communities, Park laws, Implementation, Wildilife conservation. INTRODUCTION. The contributions ... which were not taken into account at the time these national parks were ...

  13. The biogeography of host-parasite interactions

    National Research Council Canada - National Science Library

    Krasnov, Boris R; Morand, S

    2010-01-01

    ... with their disease-bearing hosts and vectors. Although we are most acutely aware of emerging diseases in our own population, all species harbour parasites of various kinds and are potential hosts for new pathogens. Indeed, the distribution of parasites with respect to host taxa and geography reveals a history of mobility along both axes. The study of emerging ...

  14. Host response in aggressive periodontitis.

    Science.gov (United States)

    Kulkarni, Cyelee; Kinane, Denis F

    2014-06-01

    It is critical to understand the underlying host responses in aggressive periodontitis to provide a better appreciation of the risk and susceptibility to this disease. Such knowledge may elucidate the etiology and susceptibility to aggressive periodontitis and directly influence treatment decisions and aid diagnosis. This review is timely in that several widely held tenets are now considered unsupportable, namely the concept that Aggregatibacter actinomycetemycomitans is the key pathogen and that chemotactic defects in polymorphonuclear leukocytes are part of the etiopathology. This review also serves to put into context key elements of the host response that may be implicated in the genetic background of aggressive periodontitis. Furthermore, key molecules unique to the host response in aggressive periodontitis may have diagnostic utility and be used in chairside clinical activity tests or as population screening markers. It is becoming increasingly appreciated that the microbial etiology of aggressive periodontitis and the histopathology of this disease are more similar to than different from that of chronic periodontitis. An important therapeutic consideration from the lack of support for A. actinomycetemycomitans as a critical pathogen here is that the widely held belief that tetracycline had a role in aggressive periodontitis therapy is now not supported and that antibiotics such as those used effectively in chronic periodontitis (metronidazole and amoxicillin) are not contraindicated. Furthermore, A. actinomycetemycomitans-related molecules, such as cytolethal distending toxin and leukotoxin, are less likely to have utility as diagnosis agents or as therapeutic targets. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Acute graft versus host disease

    Directory of Open Access Journals (Sweden)

    Vogelsang Georgia B

    2007-09-01

    Full Text Available Abstract Acute graft-versus-host disease (GVHD occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%–50% of hematopoietic stem cell transplant (HSCT recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis, liver (hepatitis/jaundice, and gastrointestinal tract (abdominal pain/diarrhea. One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis or drug reaction (causing skin rash. Acute GVHD is staged and graded (grade 0-IV by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD.

  16. Host DNA damage response factors localize to merkel cell polyomavirus DNA replication sites to support efficient viral DNA replication.

    Science.gov (United States)

    Tsang, Sabrina H; Wang, Xin; Li, Jing; Buck, Christopher B; You, Jianxin

    2014-03-01

    Accumulating evidence indicates a role for Merkel cell polyomavirus (MCPyV) in the development of Merkel cell carcinoma (MCC), making MCPyV the first polyomavirus to be clearly associated with human cancer. With the high prevalence of MCPyV infection and the increasing amount of MCC diagnosis, there is a need to better understand the virus and its oncogenic potential. In this study, we examined the relationship between the host DNA damage response (DDR) and MCPyV replication. We found that components of the ATM- and ATR-mediated DDR pathways accumulate in MCPyV large T antigen (LT)-positive nuclear foci in cells infected with native MCPyV virions. To further study MCPyV replication, we employed our previously established system, in which recombinant MCPyV episomal DNA is autonomously replicated in cultured cells. Similar to native MCPyV infection, where both MCPyV origin and LT are present, the host DDR machinery colocalized with LT in distinct nuclear foci. Immunofluorescence in situ hybridization and bromodeoxyuridine (BrdU) incorporation analysis showed that these DDR proteins and MCPyV LT in fact colocalized at the actively replicating MCPyV replication complexes, which were absent when a replication-defective LT mutant or an MCPyV-origin mutant was introduced in place of wild-type LT or wild-type viral origin. Inhibition of DDR kinases using chemical inhibitors and ATR/ATM small interfering RNA (siRNA) knockdown reduced MCPyV DNA replication without significantly affecting LT expression or the host cell cycle. This study demonstrates that these host DDR factors are important for MCPyV DNA replication, providing new insight into the host machinery involved in the MCPyV life cycle. MCPyV is the first polyomavirus to be clearly associated with human cancer. However, the MCPyV life cycle and its oncogenic mechanism remain poorly understood. In this report, we show that, in cells infected with native MCPyV virions, components of the ATM- and ATR-mediated DDR

  17. Host defences against Giardia lamblia.

    Science.gov (United States)

    Lopez-Romero, G; Quintero, J; Astiazarán-García, H; Velazquez, C

    2015-08-01

    Giardia spp. is a protozoan parasite that inhabits the upper small intestine of mammals and other species and is the aetiological agent of giardiasis. It has been demonstrated that nitric oxide, mast cells and dendritic cells are the first line of defence against Giardia. IL-6 and IL-17 play an important role during infection. Several cytokines possess overlapping functions in regulating innate and adaptive immune responses. IgA and CD4(+) T cells are fundamental to the process of Giardia clearance. It has been suggested that CD4(+) T cells play a double role during the anti-Giardia immune response. First, they activate and stimulate the differentiation of B cells to generate Giardia-specific antibodies. Second, they act through a B-cell-independent mechanism that is probably mediated by Th17 cells. Several Giardia proteins that stimulate humoral and cellular immune responses have been described. Variant surface proteins, α-1 giardin, and cyst wall protein 2 can induce host protective responses to future Giardia challenges. The characterization and evaluation of the protective potential of the immunogenic proteins that are associated with Giardia will offer new insights into host-parasite interactions and may aid in the development of an effective vaccine against the parasite. © 2015 John Wiley & Sons Ltd.

  18. Host feeding in insect parasitoids: why destructively feed upon a host that excretes an alternative?

    NARCIS (Netherlands)

    Burger, J.S.M.; Reijnen, T.M.; Van Lenteren, J.C.; Vet, L.E.M.

    2004-01-01

    Host feeding is the consumption of host tissue by the adult female parasitoid. We studied the function of destructive host feeding and its advantage over non-destructive feeding on host-derived honeydew in the whitefly parasitoid Encarsia formosa Gahan (Hymenoptera: Aphelinidae). We allowed

  19. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  20. Macroevolution of insect–plant associations: The relevance of host biogeography to host affiliation

    Science.gov (United States)

    Becerra, Judith X.; Venable, D. Lawrence

    1999-01-01

    Identifying the factors that have promoted host shifts by phytophagous insects at a macroevolutionary scale is critical to understanding the associations between plants and insects. We used molecular phylogenies of the beetle genus Blepharida and its host genus Bursera to test whether these insects have been using hosts with widely overlapping ranges over evolutionary time. We also quantified the importance of host range coincidence relative to host chemistry and host phylogenetic relatedness. Overall, the evolution of host use of these insects has not been among hosts that are geographically similar. Host chemistry is the factor that best explains their macroevolutionary patterns of host use. Interestingly, one exceptional polyphagous species has shifted among geographically close chemically dissimilar plants. PMID:10535973

  1. Host condition and host immunity affect parasite fitness in a bird - ectoparasite system

    OpenAIRE

    Tschirren, Barbara; Bischoff, Linda; Saladin, Verena; Richner, Heinz

    2007-01-01

    1. Parasites might preferentially feed on hosts in good nutritional condition as such hosts provide better resources for the parasites’ own growth, survival and reproduction. However, hosts in prime condition are also better able to develop costly immunological or physiological defence mechanisms, which in turn reduce the parasites’ reproductive success. The interplay between host condition, host defence and parasite fitness will thus play an important part in the dynamics of host–parasite sy...

  2. Hepatitis B Virus Pregenomic RNA Is Present in Virions in Plasma and Is Associated With a Response to Pegylated Interferon Alfa-2a and Nucleos(t)ide Analogues.

    Science.gov (United States)

    Jansen, L; Kootstra, Neeltje A; van Dort, Karel A; Takkenberg, R Bart; Reesink, Hendrik W; Zaaijer, Hans L

    2016-01-15

    Treatment of patients with chronic hepatitis B (CHB) with nucleos(t)ide analogues (NAs) suppresses hepatitis B virus (HBV) DNA production but does not affect the synthesis of the RNA pregenome or HBV messenger RNA. Whether HBV RNA-containing particles continue to be secreted into the bloodstream remains controversial. We developed a sensitive polymerase chain reaction (PCR) assay to quantify the HBV RNA load in a supernatant of NA-treated HepG2-2.2.15 cells and in plasma specimens from 20 patients with CHB who were receiving NA therapy and 86 patients treated with pegylated interferon alfa (Peg-IFN) and adefovir. Treatment of HepG2-2.2.15 cells with NAs for 9 days reduced HBV DNA levels (by 1.98 log10 copies/mL), whereas HBV RNA levels increased (by 0.47 log10 copies/mL; P < .05). During long-term NA treatment of patients with CHB, HBV RNA levels remained higher than HBV DNA levels. Peg-IFN-based treatment induced a stronger decrease in the HBV RNA load than NA monotherapy, and this decline was more pronounced in responders than in nonresponders. In HBV e antigen-negative patients, a lower baseline plasma HBV RNA level was independently associated with response to Peg-IFN and adefovir (odds ratio, 0.44; P = .019). Immunoprecipitation with HBV core antigen-specific antibodies after removal of the HBV surface antigen envelope demonstrated the association of plasma HBV RNA with virions. HBV RNA is present in virions in plasma specimens from patients with CHB. HBV RNA levels vary significantly from those of established viral markers during antiviral treatment, which highlights its potential as an independent marker in the evaluation of patients with CHB. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  3. Intercultural Competence in Host Students?

    DEFF Research Database (Denmark)

    Egekvist, Ulla Egidiussen; Lyngdorf, Niels Erik; Du, Xiangyun

    2016-01-01

    Although substantial work in intercultural education has been done on the intercultural competences of mobile students engaging in international study visits, there is a need to explore intercultural competences in host students. This chapter seeks to answer questions about the challenges...... and possibilities of using short-term study visits to develop these competences. Theoretically, this chapter finds inspiration in social constructivist understandings of culture and Byram’s research on intercultural competence. Empirically, the data used in this paper were derived from a study of 22 Danish lower...... experience. The study suggests that challenges and possibilities are found within the following categories: (1) Experiential learning, (2) Stereotypes and (3) Coping strategies and support....

  4. Understanding Host-Switching by Ecological Fitting.

    Directory of Open Access Journals (Sweden)

    Sabrina B L Araujo

    Full Text Available Despite the fact that parasites are highly specialized with respect to their hosts, empirical evidence demonstrates that host switching rather than co-speciation is the dominant factor influencing the diversification of host-parasite associations. Ecological fitting in sloppy fitness space has been proposed as a mechanism allowing ecological specialists to host-switch readily. That proposal is tested herein using an individual-based model of host switching. The model considers a parasite species exposed to multiple host resources. Through time host range expansion can occur readily without the prior evolution of novel genetic capacities. It also produces non-linear variation in the size of the fitness space. The capacity for host colonization is strongly influenced by propagule pressure early in the process and by the size of the fitness space later. The simulations suggest that co-adaptation may be initiated by the temporary loss of less fit phenotypes. Further, parasites can persist for extended periods in sub-optimal hosts, and thus may colonize distantly related hosts by a "stepping-stone" process.

  5. Host-to-host variation of ecological interactions in polymicrobial infections.

    Science.gov (United States)

    Mukherjee, Sayak; Weimer, Kristin E; Seok, Sang-Cheol; Ray, Will C; Jayaprakash, C; Vieland, Veronica J; Swords, W Edward; Das, Jayajit

    2014-12-04

    Host-to-host variability with respect to interactions between microorganisms and multicellular hosts are commonly observed in infection and in homeostasis. However, the majority of mechanistic models used to analyze host-microorganism relationships, as well as most of the ecological theories proposed to explain coevolution of hosts and microbes, are based on averages across a host population. By assuming that observed variations are random and independent, these models overlook the role of differences between hosts. Here, we analyze mechanisms underlying host-to-host variations of bacterial infection kinetics, using the well characterized experimental infection model of polymicrobial otitis media (OM) in chinchillas, in combination with population dynamic models and a maximum entropy (MaxEnt) based inference scheme. We find that the nature of the interactions between bacterial species critically regulates host-to-host variations in these interactions. Surprisingly, seemingly unrelated phenomena, such as the efficiency of individual bacterial species in utilizing nutrients for growth, and the microbe-specific host immune response, can become interdependent in a host population. The latter finding suggests a potential mechanism that could lead to selection of specific strains of bacterial species during the coevolution of the host immune response and the bacterial species.

  6. Road MAPs to engineer host microbiomes.

    Science.gov (United States)

    Oyserman, Ben O; Medema, Marnix H; Raaijmakers, Jos M

    2017-12-02

    Microbiomes contribute directly or indirectly to host health and fitness. Thus far, investigations into these emergent traits, referred to here as microbiome-associated phenotypes (MAPs), have been primarily qualitative and taxonomy-driven rather than quantitative and trait-based. We present the MAPs-first approach, a theoretical and experimental roadmap that involves quantitative profiling of MAPs across genetically variable hosts and subsequent identification of the underlying mechanisms. We outline strategies for developing 'modular microbiomes'-synthetic microbial consortia that are engineered in concert with the host genotype to confer different but mutually compatible MAPs to a single host or host population. By integrating host and microbial traits, these strategies will facilitate targeted engineering of microbiomes to the benefit of agriculture, human/animal health and biotechnology. Copyright © 2017. Published by Elsevier Ltd.

  7. Host specificity in phylogenetic and geographic space.

    Science.gov (United States)

    Poulin, Robert; Krasnov, Boris R; Mouillot, David

    2011-08-01

    The measurement of host specificity goes well beyond counting how many host species can successfully be used by a parasite. In particular, specificity can be assessed with respect to how closely related the host species are, or whether a parasite exploits the same or different hosts across its entire geographic range. Recent developments in the measurement of biodiversity offer a new set of analytical tools that can be used to quantify the many aspects of host specificity. We describe here the multifaceted nature of host specificity, summarize the indices available to measure its different facets one at a time or in combination, and discuss their implications for parasite evolution and disease epidemiology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Salmonella - at home in the host cell.

    Directory of Open Access Journals (Sweden)

    Preeti eMalik Kale

    2011-06-01

    Full Text Available The Gram-negative bacterium Salmonella enterica has developed an array of sophisticated tools to manipulate the host cell and establish an intracellular niche, for successful propagation as a facultative intracellular pathogen. While Salmonella exerts diverse effects on its host cell, only the cell biology of the classic trigger-mediated invasion process and the subsequent development of the Salmonella-containing vacuole have been investigated extensively. These processes are dependent on cohorts of effector proteins translocated into host cells by two type III secretion systems (T3SS, although T3SS-independent mechanisms of entry may be important for invasion of certain host cell-types. Recent studies into the intracellular lifestyle of Salmonella have provided new insights into the mechanisms used by this pathogen to modulate its intracellular environment. Here we discuss current knowledge of Salmonella-host interactions including invasion and establishment of an intracellular niche within the host.

  9. Visualizing viral transport and host infection

    Science.gov (United States)

    Son, Kwangmin; Guasto, Jeffrey; Cubillos-Ruiz, Andres; Sullivan, Matthew; Stocker, Roman; MIT Team

    2013-11-01

    A virus is a non-motile infectious agent that can only replicate inside a living host. They consist of a virus-host encounter/adsorption dynamics and subsequently the effectiveness of various tail morphologies for viral infection. Viral transport and the role of viral morphology in host-virus interactions are critical to our understanding of both ecosystem dynamics and human health, as well as to the evolution of virus morphology.

  10. Intraspecific variability in host manipulation by parasites

    OpenAIRE

    Thomas, F; Brodeur, J; Maure, F.; De Franceschi, N.; Blanchet, S.; Rigaud, T.

    2011-01-01

    Manipulative parasites have the capacity to alter a broad range of phenotypic traits in their hosts, extending from colour, morphology and behaviour. While significant attention has been devoted to describing the diversity of host manipulation among parasite clades, and testing the adaptive value of phenotypic traits that can be manipulated, there is increasing evidence that variation exists in the frequency and intensity of the changes displayed by parasitized individuals within single host-...

  11. Host Cell Copper Transporters CTR1 and ATP7A are important for Influenza A virus replication.

    Science.gov (United States)

    Rupp, Jonathan C; Locatelli, Manon; Grieser, Alexis; Ramos, Andrea; Campbell, Patricia J; Yi, Hong; Steel, John; Burkhead, Jason L; Bortz, Eric

    2017-01-23

    The essential role of copper in eukaryotic cellular physiology is known, but has not been recognized as important in the context of influenza A virus infection. In this study, we investigated the effect of cellular copper on influenza A virus replication. Influenza A/WSN/33 (H1N1) virus growth and macromolecule syntheses were assessed in cultured human lung cells (A549) where the copper concentration of the growth medium was modified, or expression of host genes involved in copper homeostasis was targeted by RNA interference. Exogenously increasing copper concentration, or chelating copper, resulted in moderate defects in viral growth. Nucleoprotein (NP) localization, neuraminidase activity assays and transmission electron microscopy did not reveal significant defects in virion assembly, morphology or release under these conditions. However, RNAi knockdown of the high-affinity copper importer CTR1 resulted in significant viral growth defects (7.3-fold reduced titer at 24 hours post-infection, p = 0.04). Knockdown of CTR1 or the trans-Golgi copper transporter ATP7A significantly reduced polymerase activity in a minigenome assay. Both copper transporters were required for authentic viral RNA synthesis and NP and matrix (M1) protein accumulation in the infected cell. These results demonstrate that intracellular copper regulates the influenza virus life cycle, with potentially distinct mechanisms in specific cellular compartments. These observations provide a new avenue for drug development and studies of influenza virus pathogenesis.

  12. Viral infection and host defense.

    Science.gov (United States)

    Carter, W A; De Clercq, E

    1974-12-27

    Double-stranded RNA, made as an intermediary substance in the replication of most, if not all, viruses, may play a much more important role in the pathogenesis and the recovery from virus infections than has hitherto been suspected. Apparently, dsRNA is used by both the challenge virus and the host cell in an attempt to gain "molecular control." Double-stranded RNA exerts a set of effects, which may be well balanced, not only at the level of the individual cell but also at the complex assemblage of these cells termed the organism (Fig. 1). In the cell, interferon synthesis is triggered, although interferon mRNA translation may not occur if dsRNA shuts off protein synthesis too quickly. In the whole organism, the disease severity will depend on how certain toxic reactions evoked by infection (such as cell necrosis and fever) are counterbalanced by an increase in the host defense mechanisms (for example, immune responsiveness and interferon production). Many aspects of the response, relating to either progress of, or recovery from, the disease, can be explained on the basis of a dsRNA. In addition to drawing attention to the biodynamic role of dsRNA, our hypothesis suggests specific experimental vectors designed to enhance our information on the molecular basis of the morbid process which occurs with viral infection. Finally, we suggest that, although the dsRNA molecule may be viewed as a rather simple unit structure, the opportunity for further diversity in the biological activity of a given dsRNA molecule always exists. Namely, each deviation from a perfectly double-helical arrangement introduces the possibility for emphasizing one biological reactivity at the expense of another. This latter structure-activity property may partially account for the extreme apparent diversity, commonly encountered, in the presentations of virologic illness. Appendix note added in proof. Subsequent to submission of this text, we have found that the potent mitogen effect of dsRNA for

  13. Host Galaxy Identification for Supernova Surveys

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Ravi R.; Kuhlmann, Steve; Kovacs, Eve; Spinka, Harold; Kessler, Richard; Goldstein, Daniel A.; Liotine, Camille; Pomian, Katarzyna; D’Andrea, Chris B.; Sullivan, Mark; Carretero, Jorge; Castander, Francisco J.; Nichol, Robert C.; Finley, David A.; Fischer, John A.; Foley, Ryan J.; Kim, Alex G.; Papadopoulos, Andreas; Sako, Masao; Scolnic, Daniel M.; Smith, Mathew; Tucker, Brad E.; Uddin, Syed; Wolf, Rachel C.; Yuan, Fang; Abbott, Tim M. C.; Abdalla, Filipe B.; Benoit-Lévy, Aurélien; Bertin, Emmanuel; Brooks, David; Rosell, Aurelio Carnero; Kind, Matias Carrasco; Cunha, Carlos E.; Costa, Luiz N. da; Desai, Shantanu; Doel, Peter; Eifler, Tim F.; Evrard, August E.; Flaugher, Brenna; Fosalba, Pablo; Gaztañaga, Enrique; Gruen, Daniel; Gruendl, Robert; James, David J.; Kuehn, Kyler; Kuropatkin, Nikolay; Maia, Marcio A. G.; Marshall, Jennifer L.; Miquel, Ramon; Plazas, Andrés A.; Romer, A. Kathy; Sánchez, Eusebio; Schubnell, Michael; Sevilla-Noarbe, Ignacio; Sobreira, Flávia; Suchyta, Eric; Swanson, Molly E. C.; Tarle, Gregory; Walker, Alistair R.; Wester, William

    2016-11-08

    Host galaxy identification is a crucial step for modern supernova (SN) surveys such as the Dark Energy Survey (DES) and the Large Synoptic Survey Telescope (LSST), which will discover SNe by the thousands. Spectroscopic resources are limited, so in the absence of real-time SN spectra these surveys must rely on host galaxy spectra to obtain accurate redshifts for the Hubble diagram and to improve photometric classification of SNe. In addition, SN luminosities are known to correlate with host-galaxy properties. Therefore, reliable identification of host galaxies is essential for cosmology and SN science. We simulate SN events and their locations within their host galaxies to develop and test methods for matching SNe to their hosts. We use both real and simulated galaxy catalog data from the Advanced Camera for Surveys General Catalog and MICECATv2.0, respectively. We also incorporate "hostless" SNe residing in undetected faint hosts into our analysis, with an assumed hostless rate of 5%. Our fully automated algorithm is run on catalog data and matches SNe to their hosts with 91% accuracy. We find that including a machine learning component, run after the initial matching algorithm, improves the accuracy (purity) of the matching to 97% with a 2% cost in efficiency (true positive rate). Although the exact results are dependent on the details of the survey and the galaxy catalogs used, the method of identifying host galaxies we outline here can be applied to any transient survey.

  14. Expatriate contact with a local host

    DEFF Research Database (Denmark)

    van Bakel, Marian; van Oudenhoven, Jan Pieter; Gerritsen, Marinel

    2017-01-01

    Social capital is a crucial factor for expatriates to employ as they cope with the demands of an international assignment. This longitudinal study used a mixed method approach to examine the social support benefits of expatriate contact with a local host. Western expatriates in the Netherlands were...... a host. This study shows that HRD professionals may develop the social capital of expatriates by bringing them into contact with a local host, which can produce more social support from host nationals. Increased social capital may lead to a higher performance at both the individual and organisational...

  15. Host plant adaptation in Drosophila mettleri populations.

    Directory of Open Access Journals (Sweden)

    Sergio Castrezana

    Full Text Available The process of local adaptation creates diversity among allopatric populations, and may eventually lead to speciation. Plant-feeding insect populations that specialize on different host species provide an excellent opportunity to evaluate the causes of ecological specialization and the subsequent consequences for diversity. In this study, we used geographically separated Drosophila mettleri populations that specialize on different host cacti to examine oviposition preference for and larval performance on an array of natural and non-natural hosts (eight total. We found evidence of local adaptation in performance on saguaro cactus (Carnegiea gigantea for populations that are typically associated with this host, and to chemically divergent prickly pear species (Opuntia spp. in a genetically isolated population on Santa Catalina Island. Moreover, each population exhibited reduced performance on the alternative host. This finding is consistent with trade-offs associated with adaptation to these chemically divergent hosts, although we also discuss alternative explanations for this pattern. For oviposition preference, Santa Catalina Island flies were more likely to oviposit on some prickly pear species, but all populations readily laid eggs on saguaro. Experiments with non-natural hosts suggest that factors such as ecological opportunity may play a more important role than host plant chemistry in explaining the lack of natural associations with some hosts.

  16. Structural host-microbiota interaction networks.

    Science.gov (United States)

    Guven-Maiorov, Emine; Tsai, Chung-Jung; Nussinov, Ruth

    2017-10-01

    Hundreds of different species colonize multicellular organisms making them "metaorganisms". A growing body of data supports the role of microbiota in health and in disease. Grasping the principles of host-microbiota interactions (HMIs) at the molecular level is important since it may provide insights into the mechanisms of infections. The crosstalk between the host and the microbiota may help resolve puzzling questions such as how a microorganism can contribute to both health and disease. Integrated superorganism networks that consider host and microbiota as a whole-may uncover their code, clarifying perhaps the most fundamental question: how they modulate immune surveillance. Within this framework, structural HMI networks can uniquely identify potential microbial effectors that target distinct host nodes or interfere with endogenous host interactions, as well as how mutations on either host or microbial proteins affect the interaction. Furthermore, structural HMIs can help identify master host cell regulator nodes and modules whose tweaking by the microbes promote aberrant activity. Collectively, these data can delineate pathogenic mechanisms and thereby help maximize beneficial therapeutics. To date, challenges in experimental techniques limit large-scale characterization of HMIs. Here we highlight an area in its infancy which we believe will increasingly engage the computational community: predicting interactions across kingdoms, and mapping these on the host cellular networks to figure out how commensal and pathogenic microbiota modulate the host signaling and broadly cross-species consequences.

  17. Host-bacterial interplay in periodontal disease

    National Research Council Canada - National Science Library

    Rudrakshi Chickanna; M. L. V. Prabhuji; M. S. V. Nagarjuna

    2015-01-01

    .... Clearly, an understanding of the host susceptibility factor in addition to microbial factors by elucidating the molecular basis offers opportunity for therapeutic manipulation of advancing periodontal destruction...

  18. Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry.

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ishii

    Full Text Available Human papillomavirus (HPV is a non-enveloped virus composed of a circular DNA genome and two capsid proteins, L1 and L2. Multiple interactions between its capsid proteins and host cellular proteins are required for infectious HPV entry, including cell attachment and internalization, intracellular trafficking and viral genome transfer into the nucleus. Using two variants of HPV type 51, the Ma and Nu strains, we have previously reported that MaL2 is required for efficient pseudovirus (PsV transduction. However, the cellular factors that confer this L2 dependency have not yet been identified. Here we report that the transport protein particle complex subunit 8 (TRAPPC8 specifically interacts with MaL2. TRAPPC8 knockdown in HeLa cells yielded reduced levels of reporter gene expression when inoculated with HPV51Ma, HPV16, and HPV31 PsVs. TRAPPC8 knockdown in HaCaT cells also showed reduced susceptibility to infection with authentic HPV31 virions, indicating that TRAPPC8 plays a crucial role in native HPV infection. Immunofluorescence microscopy revealed that the central region of TRAPPC8 was exposed on the cell surface and colocalized with inoculated PsVs. The entry of Ma, Nu, and L2-lacking PsVs into cells was equally impaired in TRAPPC8 knockdown HeLa cells, suggesting that TRAPPC8-dependent endocytosis plays an important role in HPV entry that is independent of L2 interaction. Finally, expression of GFP-fused L2 that can also interact with TRAPPC8 induced dispersal of the Golgi stack structure in HeLa cells, a phenotype also observed by TRAPPC8 knockdown. These results suggest that during viral intracellular trafficking, binding of L2 to TRAPPC8 inhibits its function resulting in Golgi destabilization, a process that may assist HPV genome escape from the trans-Golgi network.

  19. Structure, Adsorption to Host, and Infection Mechanism of Virulent Lactococcal Phage p2

    Science.gov (United States)

    Bebeacua, Cecilia; Tremblay, Denise; Farenc, Carine; Chapot-Chartier, Marie-Pierre; Sadovskaya, Irina; van Heel, Marin; Veesler, David

    2013-01-01

    Lactococcal siphophages from the 936 and P335 groups infect the Gram-positive bacterium Lactococcus lactis using receptor binding proteins (RBPs) attached to their baseplate, a large multiprotein complex at the distal part of the tail. We have previously reported the crystal and electron microscopy (EM) structures of the baseplates of phages p2 (936 group) and TP901-1 (P335 group) as well as the full EM structure of the TP901-1 virion. Here, we report the complete EM structure of siphophage p2, including its capsid, connector complex, tail, and baseplate. Furthermore, we show that the p2 tail is characterized by the presence of protruding decorations, which are related to adhesins and are likely contributed by the major tail protein C-terminal domains. This feature is reminiscent of the tail of Escherichia coli phage λ and Bacillus subtilis phage SPP1 and might point to a common mechanism for establishing initial interactions with their bacterial hosts. Comparative analyses showed that the architecture of the phage p2 baseplate differs largely from that of lactococcal phage TP901-1. We quantified the interaction of its RBP with the saccharidic receptor and determined that specificity is due to lower koff values of the RBP/saccharidic dissociation. Taken together, these results suggest that the infection of L. lactis strains by phage p2 is a multistep process that involves reversible attachment, followed by baseplate activation, specific attachment of the RBPs to the saccharidic receptor, and DNA ejection. PMID:24027307

  20. Parasite assemblages in fish hosts | Iyaji | Bio-Research

    African Journals Online (AJOL)

    A review of various factors affecting parasite assemblages in fish hosts is presented. These factors are broadly divided into two: Biotic and abiotic factors. Biotic factors such as host age and size, host size and parasites size, host specificity, host diet and host sex and their influence on the abundance and distribution of ...

  1. Noncentrosymmetric Magnets Hosting Magnetic Skyrmions.

    Science.gov (United States)

    Kanazawa, Naoya; Seki, Shinichiro; Tokura, Yoshinori

    2017-07-01

    The concept of a skyrmion, which was first introduced by Tony Skyrme in the field of particle physics, has become widespread in condensed matter physics to describe various topological orders. Skyrmions in magnetic materials have recently received particular attention; they represent vortex-like spin structures with the character of nanometric particles and produce fascinating physical properties rooted in their topological nature. Here, a series of noncentrosymmetric ferromagnets hosting skyrmions is reviewed: B20 metals, Cu2 OSeO3 , Co-Zn-Mn alloys, and GaV4 S8 , where Dzyaloshinskii-Moriya interaction plays a key role in the stabilization of skyrmion spin texture. Their topological spin arrangements and consequent emergent electromagnetic fields give rise to striking features in transport and magnetoelectric properties in metals and insulators, such as the topological Hall effect, efficient electric-drive of skyrmions, and multiferroic behavior. Such electric controllability and nanometric particle natures highlight magnetic skyrmions as a potential information carrier for high-density magnetic storage devices with excellent energy efficiency. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Identification of host proteins involved in host-pathogen interactions : a proteomics approach

    NARCIS (Netherlands)

    Vogels, M.W.

    2010-01-01

    Intracellular pathogens have evolved countless different and fascinating strategies to facilitate their multiplication and survival within host cells. Understanding the biology of intracellular pathogens requires a detailed knowledge of the molecular interactions with and contributions by the host

  3. Host-Pathogen Coupled Networks: Model for Bacillus Anthracis Interaction with Host Macrophages

    Science.gov (United States)

    2015-09-01

    AFRL-RH-WP-TR-2015-0070 HOST-PATHOGEN COUPLED NETWORKS: MODEL FOR BACILLUS ANTHRACIS INTERACTION WITH HOST MACROPHAGES Peter J. Robinson C...DATE (DD-MM-YYYY) 30-09-2015 2. REPORT TYPE Final 3. DATES COVERED (From - To) Oct 2012 – Sept. 2015 4. TITLE AND SUBTITLE Host-Pathogen Coupled...Networks: Model for Bacillus anthracis Interaction with Host Macrophages 5a. CONTRACT NUMBER In-House 5b. GRANT NUMBER NA 5c. PROGRAM ELEMENT

  4. Hepatitis C virus intracellular host interactions

    NARCIS (Netherlands)

    Liefhebber, Johanna Maaike Pieternella

    2010-01-01

    Hepatitis C virus (HCV) infects about 170 million people worldwide causing a major healthcare problem. The virus lifecycle is greatly dependent on the host-cell for effective replication. In this thesis, the intracellular interactions of the non-structural HCV proteins with the host-cell were

  5. Host factors involved in chikungunya virus replication

    NARCIS (Netherlands)

    Scholte, Florine Elisabeth Maria

    2015-01-01

    In this thesis the interplay of CHIKV with cellular (host) factors involved in its replication is addressed. An in-depth understanding of the interactions between the viral proteins and those of their host is required for the elucidation of molecular mechanisms underlying viral replication. A

  6. From Dietary Fiber to Host Physiology

    DEFF Research Database (Denmark)

    Koh, Ara; De Vadder, Filipe; Kovatcheva-Datchary, Petia

    2016-01-01

    A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial...... as energy substrates. They thus affect various physiological processes and may contribute to health and disease....

  7. Host-pathogen interactions during apoptosis

    Indian Academy of Sciences (India)

    Host pathogen interaction results in a variety of responses, which include phagocytosis of the pathogen, release of cytokines, secretion of toxins, as well as production of reactive oxygen species (ROS). Recent studies have shown that many pathogens exert control on the processes that regulate apoptosis in the host.

  8. Nestedness of ectoparasite-vertebrate host networks.

    Directory of Open Access Journals (Sweden)

    Sean P Graham

    2009-11-01

    Full Text Available Determining the structure of ectoparasite-host networks will enable disease ecologists to better understand and predict the spread of vector-borne diseases. If these networks have consistent properties, then studying the structure of well-understood networks could lead to extrapolation of these properties to others, including those that support emerging pathogens. Borrowing a quantitative measure of network structure from studies of mutualistic relationships between plants and their pollinators, we analyzed 29 ectoparasite-vertebrate host networks--including three derived from molecular bloodmeal analysis of mosquito feeding patterns--using measures of nestedness to identify non-random interactions among species. We found significant nestedness in ectoparasite-vertebrate host lists for habitats ranging from tropical rainforests to polar environments. These networks showed non-random patterns of nesting, and did not differ significantly from published estimates of nestedness from mutualistic networks. Mutualistic and antagonistic networks appear to be organized similarly, with generalized ectoparasites interacting with hosts that attract many ectoparasites and more specialized ectoparasites usually interacting with these same "generalized" hosts. This finding has implications for understanding the network dynamics of vector-born pathogens. We suggest that nestedness (rather than random ectoparasite-host associations can allow rapid transfer of pathogens throughout a network, and expand upon such concepts as the dilution effect, bridge vectors, and host switching in the context of nested ectoparasite-vertebrate host networks.

  9. Carp erythrodermatitis : host defense-pathogen interaction

    NARCIS (Netherlands)

    Pourreau, C.N.

    1990-01-01

    The outcome of a bacterial infection depends on the interaction between pathogen and host. The ability of the microbe to survive in the host depends on its invasive potential (i.e. spreading and multiplication), and its ability to obtain essential nutrients and to resist the

  10. Host genetics and dengue fever.

    Science.gov (United States)

    Xavier-Carvalho, Caroline; Cardoso, Cynthia Chester; de Souza Kehdy, Fernanda; Pacheco, Antonio Guilherme; Moraes, Milton Ozório

    2017-12-01

    Dengue is a major worldwide problem in tropical and subtropical areas; it is caused by four different viral serotypes, and it can manifest as asymptomatic, mild, or severe. Many factors interact to determine the severity of the disease, including the genetic profile of the infected patient. However, the mechanisms that lead to severe disease and eventually death have not been determined, and a great challenge is the early identification of patients who are more likely to progress to a worse health condition. Studies performed in regions with cyclic outbreaks such as Cuba, Brazil, and Colombia have demonstrated that African ancestry confers protection against severe dengue. Highlighting the host genetics as an important factor in infectious diseases, a large number of association studies between genetic polymorphisms and dengue outcomes have been published in the last two decades. The most widely used approach involves case-control studies with candidate genes, such as the HLA locus and genes for receptors, cytokines, and other immune mediators. Additionally, a Genome-Wide Association Study (GWAS) identified SNPs associated with African ethnicity that had not previously been identified in case-control studies. Despite the increasing number of publications in America, Africa, and Asia, the results are quite controversial, and a meta-analysis is needed to assess the consensus among the studies. SNPs in the MICB, TNF, CD209, FcγRIIA, TPSAB1, CLEC5A, IL10 and PLCE1 genes are associated with the risk or protection of severe dengue, and the findings have been replicated in different populations. A thorough understanding of the viral, human genetic, and immunological mechanisms of dengue and how they interact is essential for effectively preventing dengue, but also managing and treating patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Importance of host feeding for parasitoids that attack honeydew-producing hosts

    NARCIS (Netherlands)

    Burger, J.S.M.; Kormany, A.; Van Lenteren, J.C.; Vet, L.E.M.

    2005-01-01

    Insect parasitoids lay their eggs in arthropods. Some parasitoid species not only use their arthropod host for oviposition but also for feeding. Host feeding provides nutrients to the adult female parasitoid. However, in many species, host feeding destroys an opportunity to oviposit. For parasitoids

  12. Shifting preference between oviposition vs. host-feeding under changing host densities in two aphelinid parasitoids

    DEFF Research Database (Denmark)

    Yang, Nian-Wan; Ji, Lu-Lu; Lövei, Gabor L

    2012-01-01

    Destructive host-feeding is common in hymenopteran parasitoids. Such feeding may be restricted to host stages not preferred for oviposition. However, whether this is a fixed strategy or can vary according to resource levels or parasitoid needs is less clear. We tested the trade-off between host f...

  13. Insect host location: a volatile situation.

    Science.gov (United States)

    Bruce, Toby J A; Wadhams, Lester J; Woodcock, Christine M

    2005-06-01

    Locating a host plant is crucial for a phytophagous (herbivorous) insect to fulfill its nutritional requirements and to find suitable oviposition sites. Insects can locate their hosts even though the host plants are often hidden among an array of other plants. Plant volatiles play an important role in this host-location process. The recognition of a host plant by these olfactory signals could occur by using either species-specific compounds or specific ratios of ubiquitous compounds. Currently, most studies favor the second scenario, with strong evidence that plant discrimination is due to central processing of olfactory signals by the insect, rather than their initial detection. Furthermore, paired or clustered olfactory receptor neurons might enable fine-scale spatio-temporal resolution of the complex signals encountered when ubiquitous compounds are used.

  14. Host Sexual Dimorphism and Parasite Adaptation

    Science.gov (United States)

    Duneau, David; Ebert, Dieter

    2012-01-01

    In species with separate sexes, parasite prevalence and disease expression is often different between males and females. This effect has mainly been attributed to sex differences in host traits, such as immune response. Here, we make the case for how properties of the parasites themselves can also matter. Specifically, we suggest that differences between host sexes in many different traits, such as morphology and hormone levels, can impose selection on parasites. This selection can eventually lead to parasite adaptations specific to the host sex more commonly encountered, or to differential expression of parasite traits depending on which host sex they find themselves in. Parasites adapted to the sex of the host in this way can contribute to differences between males and females in disease prevalence and expression. Considering those possibilities can help shed light on host–parasite interactions, and impact epidemiological and medical science. PMID:22389630

  15. Host range of meliolaceous fungi in India

    Directory of Open Access Journals (Sweden)

    V.B. Hosagoudar

    2009-05-01

    Full Text Available The order Meliolales comprises two families, namely, Armatellaceae and Meliolaceae. Except the genera Endomeliola and Pauhia, India represents rest of the nine genera of this group. The family Armatellaceae includes two genera, namely, Armatella and Basavamyces. The family Meliolaceae includes seven genera: Amazonia, Appendiculella, Asteridiella, Ectendomeliola, Irenopsis, Meliola and Prataprajella. All these nine genera represent 613 species and infra-specific taxa known till the year 2006, infected 766 host plants belonging to 349 host genera distributed among 104 families. All the host families and the fungal genera are arranged alphabetically with their corresponding parasite and the host plant. The corresponding number after the host family represents the number of meliolaceous taxa known on the members of that family.

  16. Codivergence of mycoviruses with their hosts.

    Directory of Open Access Journals (Sweden)

    Markus Göker

    Full Text Available BACKGROUND: The associations between pathogens and their hosts are complex and can result from any combination of evolutionary events such as codivergence, switching, and duplication of the pathogen. Mycoviruses are RNA viruses which infect fungi and for which natural vectors are so far unknown. Thus, lateral transfer might be improbable and codivergence their dominant mode of evolution. Accordingly, mycoviruses are a suitable target for statistical tests of virus-host codivergence, but inference of mycovirus phylogenies might be difficult because of low sequence similarity even within families. METHODOLOGY: We analyzed here the evolutionary dynamics of all mycovirus families by comparing virus and host phylogenies. Additionally, we assessed the sensitivity of the co-phylogenetic tests to the settings for inferring virus trees from their genome sequences and approximate, taxonomy-based host trees. CONCLUSIONS: While sequence alignment filtering modes affected branch support, the overall results of the co-phylogenetic tests were significantly influenced only by the number of viruses sampled per family. The trees of the two largest families, Partitiviridae and Totiviridae, were significantly more similar to those of their hosts than expected by chance, and most individual host-virus links had a significant positive impact on the global fit, indicating that codivergence is the dominant mode of virus diversification. However, in this regard mycoviruses did not differ from closely related viruses sampled from non-fungus hosts. The remaining virus families were either dominated by other evolutionary modes or lacked an apparent overall pattern. As this negative result might be caused by insufficient taxon sampling, the most parsimonious hypothesis still is that host-parasite evolution is basically the same in all mycovirus families. This is the first study of mycovirus-host codivergence, and the results shed light not only on how mycovirus biology

  17. Codivergence of Mycoviruses with Their Hosts

    Science.gov (United States)

    Göker, Markus; Scheuner, Carmen; Klenk, Hans-Peter; Stielow, J. Benjamin; Menzel, Wulf

    2011-01-01

    Background The associations between pathogens and their hosts are complex and can result from any combination of evolutionary events such as codivergence, switching, and duplication of the pathogen. Mycoviruses are RNA viruses which infect fungi and for which natural vectors are so far unknown. Thus, lateral transfer might be improbable and codivergence their dominant mode of evolution. Accordingly, mycoviruses are a suitable target for statistical tests of virus-host codivergence, but inference of mycovirus phylogenies might be difficult because of low sequence similarity even within families. Methodology We analyzed here the evolutionary dynamics of all mycovirus families by comparing virus and host phylogenies. Additionally, we assessed the sensitivity of the co-phylogenetic tests to the settings for inferring virus trees from their genome sequences and approximate, taxonomy-based host trees. Conclusions While sequence alignment filtering modes affected branch support, the overall results of the co-phylogenetic tests were significantly influenced only by the number of viruses sampled per family. The trees of the two largest families, Partitiviridae and Totiviridae, were significantly more similar to those of their hosts than expected by chance, and most individual host-virus links had a significant positive impact on the global fit, indicating that codivergence is the dominant mode of virus diversification. However, in this regard mycoviruses did not differ from closely related viruses sampled from non-fungus hosts. The remaining virus families were either dominated by other evolutionary modes or lacked an apparent overall pattern. As this negative result might be caused by insufficient taxon sampling, the most parsimonious hypothesis still is that host-parasite evolution is basically the same in all mycovirus families. This is the first study of mycovirus-host codivergence, and the results shed light not only on how mycovirus biology affects their co

  18. Crimean-Congo hemorrhagic fever virus entry into host cells occurs through the multivesicular body and requires ESCRT regulators.

    Directory of Open Access Journals (Sweden)

    Olena Shtanko

    2014-09-01

    Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is a tick-borne bunyavirus causing outbreaks of severe disease in humans, with a fatality rate approaching 30%. There are no widely accepted therapeutics available to prevent or treat the disease. CCHFV enters host cells through clathrin-mediated endocytosis and is subsequently transported to an acidified compartment where the fusion of virus envelope with cellular membranes takes place. To better understand the uptake pathway, we sought to identify host factors controlling CCHFV transport through the cell. We demonstrate that after passing through early endosomes in a Rab5-dependent manner, CCHFV is delivered to multivesicular bodies (MVBs. Virus particles localized to MVBs approximately 1 hour after infection and affected the distribution of the organelle within cells. Interestingly, blocking Rab7 activity had no effect on association of the virus with MVBs. Productive virus infection depended on phosphatidylinositol 3-kinase (PI3K activity, which meditates the formation of functional MVBs. Silencing Tsg101, Vps24, Vps4B, or Alix/Aip1, components of the endosomal sorting complex required for transport (ESCRT pathway controlling MVB biogenesis, inhibited infection of wild-type virus as well as a novel pseudotyped vesicular stomatitis virus (VSV bearing CCHFV glycoprotein, supporting a role for the MVB pathway in CCHFV entry. We further demonstrate that blocking transport out of MVBs still allowed virus entry while preventing vesicular acidification, required for membrane fusion, trapped virions in the MVBs. These findings suggest that MVBs are necessary for infection and are the sites of virus-endosome membrane fusion.

  19. Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration.

    Science.gov (United States)

    Zurnic, Irena; Hütter, Sylvia; Rzeha, Ute; Stanke, Nicole; Reh, Juliane; Müllers, Erik; Hamann, Martin V; Kern, Tobias; Gerresheim, Gesche K; Lindel, Fabian; Serrao, Erik; Lesbats, Paul; Engelman, Alan N; Cherepanov, Peter; Lindemann, Dirk

    2016-08-01

    Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells.

  20. A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice.

    Science.gov (United States)

    Ogembo, Javier Gordon; Muraswki, Matthew R; McGinnes, Lori W; Parcharidou, Agapi; Sutiwisesak, Rujapak; Tison, Timelia; Avendano, Juan; Agnani, Deep; Finberg, Robert W; Morrison, Trudy G; Fingeroth, Joyce D

    2015-02-06

    Epstein-Barr virus (EBV), an oncogenic gammaherpesvirus, causes acute infectious mononucleosis (AIM) and is linked to the development of several human malignancies. There is an urgent need for a vaccine that is safe, prevents infection and/or limits disease. Unique among human herpesviruses, glycoprotein (gp)350/220, which initiates EBV attachment to susceptible host cells, is the major ligand on the EBV envelope and is highly conserved. Interaction between gp350/220 and complement receptor type 2 (CR2)/CD21 and/or (CR1)/CD35 on B-cells is required for infection. Potent antibody responses to gp350/220 occur in animal models and humans. Thus, gp350/220 provides an attractive candidate for prophylactic subunit vaccine development. However, in a recent Phase II clinical trial immunization with soluble recombinant gp350 reduced the incidence of AIM, but did not prevent infection. Despite various attempts to produce an EBV vaccine, no vaccine is licensed. Herein we describe a sub-unit vaccine against EBV based on a novel Newcastle disease virus (NDV)-virus-like particle (VLP) platform consisting of EBVgp350/220 ectodomain fused to NDV-fusion (F) protein. The chimeric protein EBVgp350/220-F is incorporated into the membrane of a VLP composed of the NDV matrix and nucleoprotein. The particles resemble native EBV in diameter and shape and bind CD21 and CD35. Immunization of BALB/c mice with EBVgp350/220-F VLPs elicited strong, long-lasting neutralizing antibody responses when assessed in vitro. This chimeric VLP is predicted to provide a superior safety profile as it is efficiently produced in Chinese hamster ovary (CHO) cells using a platform devoid of human nucleic acid and EBV-transforming genes.

  1. Mosquito host selection varies seasonally with host availability and mosquito density.

    Directory of Open Access Journals (Sweden)

    Tara C Thiemann

    2011-12-01

    Full Text Available Host selection by vector mosquitoes is a critical component of virus proliferation, particularly for viruses such as West Nile (WNV that are transmitted enzootically to a variety of avian hosts, and tangentially to dead-end hosts such as humans. Culex tarsalis is a principal vector of WNV in rural areas of western North America. Based on previous work, Cx. tarsalis utilizes a variety of avian and mammalian hosts and tends to feed more frequently on mammals in the late summer than during the rest of the year. To further explore this and other temporal changes in host selection, bloodfed females were collected at a rural farmstead and heron nesting site in Northern California from May 2008 through May 2009, and bloodmeal hosts identified using either a microsphere-based array or by sequencing of the mitochondrial cytochrome c oxidase I (COI gene. Host composition during summer was dominated by four species of nesting Ardeidae. In addition, the site was populated with various passerine species as well as domestic farm animals and humans. When present, Cx. tarsalis fed predominantly (>80% upon the ardeids, with Black-crowned Night-Herons, a highly competent WNV host, the most prevalent summer host. As the ardeids fledged and left the area and mosquito abundance increased in late summer, Cx. tarsalis feeding shifted to include more mammals, primarily cattle, and a high diversity of avian species. In the winter, Yellow-billed Magpies and House Sparrows were the predominant hosts, and Yellow-billed Magpies and American Robins were fed upon more frequently than expected given their relative abundance. These data demonstrated that host selection was likely based both on host availability and differences in utilization, that the shift of bloodfeeding to include more mammalian hosts was likely the result of both host availability and increased mosquito abundance, and that WNV-competent hosts were fed upon by Cx. tarsalis throughout the year.

  2. Peptides designed to spatially depict the Epstein-Barr virus major virion glycoprotein gp350 neutralization epitope elicit antibodies that block virus-neutralizing antibody 72A1 interaction with the native gp350 molecule.

    Science.gov (United States)

    Tanner, Jerome E; Coinçon, Mathieu; Leblond, Valérie; Hu, Jing; Fang, Janey M; Sygusch, Jurgen; Alfieri, Caroline

    2015-05-01

    Epstein-Barr virus (EBV) is the etiologic agent of infectious mononucleosis and the root cause of B-cell lymphoproliferative disease in individuals with a weakened immune system, as well as a principal cofactor in nasopharyngeal carcinoma, various lymphomas, and other cancers. The EBV major virion surface glycoprotein gp350 is viewed as the best vaccine candidate to prevent infectious mononucleosis in healthy EBV-naive persons and EBV-related cancers in at-risk individuals. Previous epitope mapping of gp350 revealed only one dominant neutralizing epitope, which has been shown to be the target of the monoclonal antibody 72A1. Computer modeling of the 72A1 antibody interaction with the gp350 amino terminus was used to identify gp350 amino acids that could form strong ionic, electrostatic, or hydrogen bonds with the 72A1 antibody. Peptide DDRTTLQLAQNPVYIPETYPYIKWDN (designated peptide 2) and peptide GSAKPGNGSYFASVKTEMLGNEID (designated peptide 3) were designed to spatially represent the gp350 amino acids predicted to interact with the 72A1 antibody paratope. Peptide 2 bound to the 72A1 antibody and blocked 72A1 antibody recognition of the native gp350 molecule. Peptide 2 and peptide 3 were recognized by human IgG and shown to elicit murine antibodies that could target gp350 and block its recognition by the 72A1 antibody. This work provides a structural mapping of the interaction between the EBV-neutralizing antibody 72A1 and the major virion surface protein gp350. gp350 mimetic peptides that spatially depict the EBV-neutralizing epitope would be useful as a vaccine to focus the immune system exclusively to this important virus epitope. The production of virus-neutralizing antibodies targeting the Epstein-Barr virus (EBV) major surface glycoprotein gp350 is important for the prevention of infectious mononucleosis and EBV-related cancers. The data presented here provide the first in silico map of the gp350 interaction with a virus-blocking monoclonal antibody

  3. Host response to biomaterials the impact of host response on biomaterial selection

    CERN Document Server

    Badylak, Stephen F

    2015-01-01

    Host Response to Biomaterials: The Impact of Host Response on Biomaterial Selection explains the various categories of biomaterials and their significance for clinical applications, focusing on the host response to each biomaterial. It is one of the first books to connect immunology and biomaterials with regard to host response. The text also explores the role of the immune system in host response, and covers the regulatory environment for biomaterials, along with the benefits of synthetic versus natural biomaterials, and the transition from simple to complex biomaterial solutions. Fiel

  4. Host seeking parasitic nematodes use specific odors to assess host resources.

    Science.gov (United States)

    Baiocchi, Tiffany; Lee, Grant; Choe, Dong-Hwan; Dillman, Adler R

    2017-07-24

    Entomopathogenic nematodes (EPNs) are insect parasites used as biological control agents. Free-living infective juveniles (IJs) of EPNs employ host-seeking behaviors to locate suitable hosts for infection. We found that EPNs can differentiate between naïve and infected hosts, and that host attractiveness changes over time in a species-specific manner. We used solid-phase microextraction and gas chromatography/mass spectrometry to identify volatile chemical cues that may relay information about a potential host's infection status and resource availability. Among the chemicals identified from the headspace of infected hosts, 3-Methyl-2-buten-1-ol (prenol) and 3-Hydroxy-2-butanone (AMC) were selected for further behavioral assays due to their temporal correlation with the behavioral changes of IJs towards the infected hosts. Both compounds were repulsive to IJs of Steinernema glaseri and S. riobrave in a dose-dependent manner when applied on an agar substrate. Furthermore, the repulsive effects of prenol were maintained when co-presented with the uninfected host odors, overriding attraction to uninfected hosts. Prenol was attractive to dauers of some free-living nematodes and insect larvae. These data suggest that host-associated chemical cues may have several implications in EPN biology, not only as signals for avoidance and dispersal of conspecifics, but also as attractants for new potential hosts.

  5. Host allometry influences the evolution of parasite host-generalism: theory and meta-analysis.

    Science.gov (United States)

    Walker, Josephine G; Hurford, Amy; Cable, Jo; Ellison, Amy R; Price, Stephen J; Cressler, Clayton E

    2017-05-05

    Parasites vary widely in the diversity of hosts they infect: some parasite species are specialists-infecting just a single host species, while others are generalists, capable of infecting many. Understanding the factors that drive parasite host-generalism is of basic biological interest, but also directly relevant to predicting disease emergence in new host species, identifying parasites that are likely to have unidentified additional hosts, and assessing transmission risk. Here, we use mathematical models to investigate how variation in host body size and environmental temperature affect the evolution of parasite host-generalism. We predict that parasites are more likely to evolve a generalist strategy when hosts are large-bodied, when variation in host body size is large, and in cooler environments. We then explore these predictions using a newly updated database of over 20 000 fish-macroparasite associations. Within the database we see some evidence supporting these predictions, but also highlight mismatches between theory and data. By combining these two approaches, we establish a theoretical basis for interpreting empirical data on parasites' host specificity and identify key areas for future work that will help untangle the drivers of parasite host-generalism.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'. © 2017 The Authors.

  6. Host Genotype and Coinfection Modify the Relationship of within and between Host Transmission.

    Science.gov (United States)

    Susi, Hanna; Vale, Pedro F; Laine, Anna-Liisa

    2015-08-01

    Variation in individual-level disease transmission is well documented, but the underlying causes of this variation are challenging to disentangle in natural epidemics. In general, within-host replication is critical in determining the extent to which infected hosts shed transmission propagules, but which factors cause variation in this relationship are poorly understood. Here, using a plant host, Plantago lanceolata, and the powdery mildew fungus Podosphaera plantaginis, we quantify how the distinct stages of within-host spread (autoinfection), spore release, and successful transmission to new hosts (alloinfection) are influenced by host genotype, pathogen genotype, and the coinfection status of the host. We find that within-host spread alone fails to predict transmission rates, as this relationship is modified by genetic variation in hosts and pathogens. Their contributions change throughout the course of the epidemic. Host genotype and coinfection had particularly pronounced effects on the dynamics of spore release from infected hosts. Confidently predicting disease spread from local levels of individual transmission, therefore, requires a more nuanced understanding of genotype-specific infection outcomes. This knowledge is key to better understanding the drivers of epidemiological dynamics and the resulting evolutionary trajectories of infectious disease.

  7. Metalloporphyrin hosts for supramolecular chemistry of fullerenes.

    Science.gov (United States)

    Tashiro, Kentaro; Aida, Takuzo

    2007-02-01

    This paper is a tutorial review of the host-guest chemistry of fullerenes and metalloporphyrin. Among various host molecules for fullerenes, cyclic hosts composed of metalloporphyrin moieties possess one of the highest affinities toward fullerenes, which can be widely tuned simply by changing the central metal ions of the porphyrin moieties. Inclusion of fullerenes occurs not only by van der Waals interactions but also, in some cases, via pi-electronic charge-transfer from the host metalloporphyrin moieties to the guest fullerenes. Fullerenes such as C(120), upon inclusion with cyclic metalloporphyrin dimers, show an oscillatory motion within the host cavity, whose frequency reflects the solvation/desolvation dynamics of the fullerenes. A molecularly engineered metalloporphyrin host with a self-assembling capability allows a guest-directed formation of a supramolecular peapod, where included fullerenes, as peas, are aligned along the self-assembled metalloporphyrin nanotube, as a pod. Furthermore, certain metalloporphyrin hosts are applicable to the selective extraction of low-abundance higher fullerenes from an industrial production source and also allow spectroscopic discrimination of chiral fullerenes.

  8. Bartonella entry mechanisms into mammalian host cells.

    Science.gov (United States)

    Eicher, Simone C; Dehio, Christoph

    2012-08-01

    The Gram-negative genus Bartonella comprises arthropod-borne pathogens that typically infect mammals in a host-specific manner. Bartonella bacilliformis and Bartonella quintana are human-specific pathogens, while several zoonotic bartonellae specific for diverse animal hosts infect humans as an incidental host. Clinical manifestations of Bartonella infections range from mild symptoms to life-threatening disease. Following transmission by blood-sucking arthropods or traumatic contact with infected animals, bartonellae display sequential tropisms towards endothelial and possibly other nucleated cells and erythrocytes, the latter in a host-specific manner. Attachment to the extracellular matrix (ECM) and to nucleated cells is mediated by surface-exposed bacterial adhesins, in particular trimeric autotransporter adhesins (TAAs). The subsequent engulfment of the pathogen into a vacuolar structure follows a unique series of events whereby the pathogen avoids the endolysosomal compartments. For Bartonella henselae and assumingly most other species, the infection process is aided at different steps by Bartonella effector proteins (Beps). They are injected into host cells through the type IV secretion system (T4SS) VirB/D4 and subvert host cellular functions to favour pathogen uptake. Bacterial binding to erythrocytes is mediated by Trw, another T4SS, in a strictly host-specific manner, followed by pathogen-forced uptake involving the IalB invasin and subsequent replication and persistence within a membrane-bound intra-erythrocytic compartment. © 2012 Blackwell Publishing Ltd.

  9. Determinants Involved in Hepatitis C Virus and GB Virus B Primate Host Restriction

    Science.gov (United States)

    Marnata, Caroline; Saulnier, Aure; Mompelat, Dimitri; Krey, Thomas; Cohen, Lisette; Boukadida, Célia; Warter, Lucile; Fresquet, Judith; Vasiliauskaite, Ieva; Escriou, Nicolas; Cosset, François-Loïc; Rey, Felix A.; Lanford, Robert E.; Karayiannis, Peter; Rose, Nicola J.; Lavillette, Dimitri

    2015-01-01

    ABSTRACT Hepatitis C virus (HCV) only infects humans and chimpanzees, while GB virus B (GBV-B), another hepatotropic hepacivirus, infects small New World primates (tamarins and marmosets). In an effort to develop an immunocompetent small primate model for HCV infection to study HCV pathogenesis and vaccine approaches, we investigated the HCV life cycle step(s) that may be restricted in small primate hepatocytes. First, we found that replication-competent, genome-length chimeric HCV RNAs encoding GBV-B structural proteins in place of equivalent HCV sequences designed to allow entry into simian hepatocytes failed to induce viremia in tamarins following intrahepatic inoculation, nor did they lead to progeny virus in permissive, transfected human Huh7.5 hepatoma cells upon serial passage. This likely reflected the disruption of interactions between distantly related structural and nonstructural proteins that are essential for virion production, whereas such cross talk could be restored in similarly designed HCV intergenotypic recombinants via adaptive mutations in NS3 protease or helicase domains. Next, HCV entry into small primate hepatocytes was examined directly using HCV-pseudotyped retroviral particles (HCV-pp). HCV-pp efficiently infected tamarin hepatic cell lines and primary marmoset hepatocyte cultures through the use of the simian CD81 ortholog as a coreceptor, indicating that HCV entry is not restricted in small New World primate hepatocytes. Furthermore, we observed genomic replication and modest virus secretion following infection of primary marmoset hepatocyte cultures with a highly cell culture-adapted HCV strain. Thus, HCV can successfully complete its life cycle in primary simian hepatocytes, suggesting the possibility of adapting some HCV strains to small primate hosts. IMPORTANCE Hepatitis C virus (HCV) is an important human pathogen that infects over 150 million individuals worldwide and leads to chronic liver disease. The lack of a small animal

  10. Determinants Involved in Hepatitis C Virus and GB Virus B Primate Host Restriction.

    Science.gov (United States)

    Marnata, Caroline; Saulnier, Aure; Mompelat, Dimitri; Krey, Thomas; Cohen, Lisette; Boukadida, Célia; Warter, Lucile; Fresquet, Judith; Vasiliauskaite, Ieva; Escriou, Nicolas; Cosset, François-Loïc; Rey, Felix A; Lanford, Robert E; Karayiannis, Peter; Rose, Nicola J; Lavillette, Dimitri; Martin, Annette

    2015-12-01

    Hepatitis C virus (HCV) only infects humans and chimpanzees, while GB virus B (GBV-B), another hepatotropic hepacivirus, infects small New World primates (tamarins and marmosets). In an effort to develop an immunocompetent small primate model for HCV infection to study HCV pathogenesis and vaccine approaches, we investigated the HCV life cycle step(s) that may be restricted in small primate hepatocytes. First, we found that replication-competent, genome-length chimeric HCV RNAs encoding GBV-B structural proteins in place of equivalent HCV sequences designed to allow entry into simian hepatocytes failed to induce viremia in tamarins following intrahepatic inoculation, nor did they lead to progeny virus in permissive, transfected human Huh7.5 hepatoma cells upon serial passage. This likely reflected the disruption of interactions between distantly related structural and nonstructural proteins that are essential for virion production, whereas such cross talk could be restored in similarly designed HCV intergenotypic recombinants via adaptive mutations in NS3 protease or helicase domains. Next, HCV entry into small primate hepatocytes was examined directly using HCV-pseudotyped retroviral particles (HCV-pp). HCV-pp efficiently infected tamarin hepatic cell lines and primary marmoset hepatocyte cultures through the use of the simian CD81 ortholog as a coreceptor, indicating that HCV entry is not restricted in small New World primate hepatocytes. Furthermore, we observed genomic replication and modest virus secretion following infection of primary marmoset hepatocyte cultures with a highly cell culture-adapted HCV strain. Thus, HCV can successfully complete its life cycle in primary simian hepatocytes, suggesting the possibility of adapting some HCV strains to small primate hosts. Hepatitis C virus (HCV) is an important human pathogen that infects over 150 million individuals worldwide and leads to chronic liver disease. The lack of a small animal model for this

  11. Mesoscale spatiotemporal variability in a complex host-parasite system influenced by intermediate host body size.

    Science.gov (United States)

    Rodríguez, Sara M; Valdivia, Nelson

    2017-01-01

    Parasites are essential components of natural communities, but the factors that generate skewed distributions of parasite occurrences and abundances across host populations are not well understood. Here, we analyse at a seascape scale the spatiotemporal relationships of parasite exposure and host body-size with the proportion of infected hosts (i.e., prevalence) and aggregation of parasite burden across ca. 150 km of the coast and over 22 months. We predicted that the effects of parasite exposure on prevalence and aggregation are dependent on host body-sizes. We used an indirect host-parasite interaction in which migratory seagulls, sandy-shore molecrabs, and an acanthocephalan worm constitute the definitive hosts, intermediate hosts, and endoparasite, respectively. In such complex systems, increments in the abundance of definitive hosts imply increments in intermediate hosts' exposure to the parasite's dispersive stages. Linear mixed-effects models showed a significant, albeit highly variable, positive relationship between seagull density and prevalence. This relationship was stronger for small (cephalothorax length >15 mm) than large molecrabs (parasites than small molecrabs. The analysis of the variance-to-mean ratio of per capita parasite burden showed no relationship between seagull density and mean parasite aggregation across host populations. However, the amount of unexplained variability in aggregation was strikingly higher in larger than smaller intermediate hosts. This unexplained variability was driven by a decrease in the mean-variance scaling in heavily infected large molecrabs. These results show complex interdependencies between extrinsic and intrinsic population attributes on the structure of host-parasite interactions. We suggest that parasite accumulation-a characteristic of indirect host-parasite interactions-and subsequent increasing mortality rates over ontogeny underpin size-dependent host-parasite dynamics.

  12. Deployable Emergency Shutoff Device Blocks High-Velocity Fluid Flows

    Science.gov (United States)

    Nabors, Sammy A.

    2015-01-01

    NASA's Marshall Space Flight Center has developed a device and method for blocking the flow of fluid from an open pipe. Motivated by the sea-bed oil-drilling catastrophe in the Gulf of Mexico in 2010, NASA innovators designed the device to plug, control, and meter the flow of gases and liquids. Anchored with friction fittings, spikes, or explosively activated fasteners, the device is well-suited for harsh environments and high fluid velocities and pressures. With the addition of instrumentation, it can also be used as a variable area flow metering valve that can be set based upon flow conditions. With robotic additions, this patent-pending innovation can be configured to crawl into a pipe then anchor and activate itself to block or control fluid flow.

  13. Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions.

    Science.gov (United States)

    Freudenberger, Nora; Meyer, Tina; Groitl, Peter; Dobner, Thomas; Schreiner, Sabrina

    2018-02-15

    Human adenoviruses (HAdV) are nonenveloped viruses containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear pore complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood. The core protein V is speculated to bridge the core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli. Here, we show that protein V contains conserved SUMO conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced SUMOylation of the protein; thus, protein V represents a novel target of the host SUMOylation machinery. To understand the role of protein V SUMO posttranslational modification during productive HAdV infection, we generated a replication-competent HAdV with SCM mutations within the protein V coding sequence. Phenotypic analyses revealed that these SCM mutations are beneficial for adenoviral replication. Blocking protein V SUMOylation at specific sites shifts the onset of viral DNA replication to earlier time points during infection and promotes viral gene expression. Simultaneously, the altered kinetics within the viral life cycle are accompanied by more efficient proteasomal degradation of host determinants and increased virus progeny production than that observed during wild-type infection. Taken together, our studies show that protein V SUMOylation reduces virus growth; hence, protein V SUMOylation represents an important novel aspect of the host antiviral strategy to limit virus replication and thereby points to potential intervention strategies. IMPORTANCE Many decades of research have revealed that HAdV structural proteins promote viral entry and mainly physical stability of the viral genome in the capsid. Our work over the last years showed that this

  14. H1N1 influenza A outbreak among young medical staff members who received single dose of non-adjuvanted split-virion 2009 H1N1 vaccine.

    Science.gov (United States)

    Ohara, Mamiko; Tsubokura, Masaharu; Naoto, Hosokawa; Kami, Masahiro; Mochizuki, Takahiro

    2011-01-01

    We experienced an H1N1 influenza A outbreak among medical staff members who had received a vaccination. To investigate the preventive effects of the H1N1 influenza vaccine on the H1N1 influenza A infection, we examined the data on the medical staff members and patients with confirmed H1N1 influenza A or influenza-like illness retrospectively. Approximately half of the young individuals under 30 years of age developed H1N1 influenza A, while the diagnosis was established in 3% of medical staff over the age of 30 and 0.9% of patients with a median age of 67. The mechanism for association between age and the risk of H1N1 infection is unclear; however, it might have been associated with an age-related increase in the prevalence of neutralizing antibody titers against the 2009 H1N1 influenza A as indicated by previous reports. This study showed that current Japanese H1N1 influenza A vaccine program using one dose of non-adjuvant split-virion 2009 H1N1 vaccine with 7.5 μg hemagglutinin had a limited preventive effect on H1N1 influenza A infection in adults under 30 years of age.

  15. Generation of H9 T-cells stably expressing a membrane-bound form of the cytoplasmic tail of the Env-glycoprotein: lack of transcomplementation of defective HIV-1 virions encoding C-terminally truncated Env

    Directory of Open Access Journals (Sweden)

    Bosch Valerie

    2006-05-01

    Full Text Available Abstract H9-T-cells do not support the replication of mutant HIV-1 encoding Env protein lacking its long cytoplasmic C-terminal domain (Env-CT. Here we describe the generation of a H9-T-cell population constitutively expressing the HIV-1 Env-CT protein domain anchored in the cellular membrane by it homologous membrane-spanning domain (TMD. We confirmed that the Env-TMD-CT protein was associated with cellular membranes, that its expression did not have any obvious cytotoxic effects on the cells and that it did not affect wild-type HIV-1 replication. However, as measured in both a single-round assay as well as in spreading infections, replication competence of mutant pNL-Tr712, lacking the Env-CT, was not restored in this H9 T-cell population. This means that the Env-CT per se cannot transcomplement the replication block of HIV-1 virions encoding C-terminally truncated Env proteins and suggests that the Env-CT likely exerts its function only in the context of the complete Env protein.

  16. The evolution of host-symbiont dependence

    NARCIS (Netherlands)

    Fisher, Roberta M.; Henry, Lee M.; Cornwallis, Charlie K.; Kiers, E. Toby; West, Stuart A.

    2017-01-01

    Organisms across the tree of life form symbiotic partnerships with microbes for metabolism, protection and resources. While some hosts evolve extreme dependence on their symbionts, others maintain facultative associations. Explaining this variation is fundamental to understanding when symbiosis can

  17. CERN to host conference on information society

    CERN Multimedia

    CERN will host a conference on the Role of Science in the Information Society (RSIS) in December. This conference will focus on ensuring that the information society benefits people to the greatest extent possible, especially in developing regions.

  18. Host-bacterial interplay in periodontal disease

    Directory of Open Access Journals (Sweden)

    Rudrakshi Chickanna

    2015-01-01

    Full Text Available A literature search was performed using MEDLINE (PubMed and other electronic basis from 1991 to 2014. Search included books and journals based on the systematic and critical reviews, in vitro and in vivo clinical studies on molecular basis of host microbial interactions. Clearly, an understanding of the host susceptibility factor in addition to microbial factors by elucidating the molecular basis offers opportunity for therapeutic manipulation of advancing periodontal destruction. One of the hallmarks of pathogenesis is the ability of pathogenic organisms to invade surrounding tissues and to evade the host defence. This paper focuses the general overview of molecular mechanisms involved in the microbiota and host response to bacterial inimical behavior in periodontics.

  19. Towards host-directed therapies for tuberculosis.

    Science.gov (United States)

    Zumla, Alimuddin; Maeurer, Markus; Chakaya, Jeremiah; Hoelscher, Michael; Ntoumi, Francine; Rustomjee, Roxana; Vilaplana, Cristina; Yeboah-Manu, Dorothy; Rasolof, Voahangy; Munderi, Paula; Singh, Nalini; Aklillu, Eleni; Padayatchi, Nesri; Macete, Eusebio; Kapata, Nathan; Mulenga, Modest; Kibiki, Gibson; Mfinanga, Sayoki; Nyirenda, Thomas; Maboko, Leonard; Garcia-Basteiro, Alberto; Rakotosamimanana, Niaina; Bates, Matthew; Mwaba, Peter; Reither, Klaus; Gagneux, Sebastien; Edwards, Sarah; Mfinanga, Elirehema; Abdulla, Salim; Cardona, Pere-Joan; Russell, James B W; Gant, Vanya; Noursadeghi, Mahdad; Elkington, Paul; Bonnet, Maryline; Menendez, Clara; Dieye, Tandakha N; Diarra, Bassirou; Maiga, Almoustapha; Aseffa, Abraham; Parida, Shreemanta; Wejse, Christian; Petersen, Eskild; Kaleebu, Pontiano; Oliver, Matt; Craig, Gill; Corrah, Tumena; Tientcheu, Leopold; Antonio, Martin; Rao, Martin; McHugh, Timothy D; Sheikh, Aziz; Ippolito, Giuseppe; Ramjee, Gita; Kaufmann, Stefan H E; Churchyard, Gavin; Steyn, Andrie; Grobusch, Martin; Sanne, Ian; Martinson, Neil; Madansein, Rajhmun; Wilkinson, Robert J; Mayosi, Bongani; Schito, Marco; Wallis, Robert S

    2015-08-01

    The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies.

  20. Towards host-directed therapies for tuberculosis

    NARCIS (Netherlands)

    Zumla, Alimuddin; Maeurer, Markus; Chakaya, Jeremiah; Hoelscher, Michael; Ntoumi, Francine; Rustomjee, Roxana; Vilaplana, Cristina; Yeboah-Manu, Dorothy; Rasolof, Voahangy; Munderi, Paula; Singh, Nalini; Aklillu, Eleni; Padayatchi, Nesri; Macete, Eusebio; Kapata, Nathan; Mulenga, Modest; Kibiki, Gibson; Mfinanga, Sayoki; Nyirenda, Thomas; Maboko, Leonard; Garcia-Basteiro, Alberto; Rakotosamimanana, Niaina; Bates, Matthew; Mwaba, Peter; Reither, Klaus; Gagneux, Sebastien; Edwards, Sarah; Mfinanga, Elirehema; Abdulla, Salim; Cardona, Pere-Joan; Russell, James B. W.; Gant, Vanya; Noursadeghi, Mahdad; Elkington, Paul; Bonnet, Maryline; Menendez, Clara; Dieye, Tandakha N.; Diarra, Bassirou; Maiga, Almoustapha; Aseffa, Abraham; Parida, Shreemanta; Wejse, Christian; Petersen, Eskild; Kaleebu, Pontiano; Oliver, Matt; Craig, Gill; Corrah, Tumena; Tientcheu, Leopold; Antonio, Martin; Rao, Martin; McHugh, Timothy D.; Sheikh, Aziz; Ippolito, Giuseppe; Ramjee, Gita; Kaufmann, Stefan H. E.; Churchyard, Gavin; Steyn, Andrie; Grobusch, Martin; Sanne, Ian; Martinson, Neil; Madansein, Rajhmun; Wilkinson, Robert J.; Mayosi, Bongani; Schito, Marco; Wallis, Robert S.

    2015-01-01

    The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies

  1. Circumnuclear Structures in Megamaser Host Galaxies

    Science.gov (United States)

    Pjanka, Patryk; Greene, Jenny E.; Seth, Anil C.; Braatz, James A.; Henkel, Christian; Lo, Fred K. Y.; Läsker, Ronald

    2017-08-01

    Using the Hubble Space Telescope, we identify circumnuclear (100-500 pc scale) structures in nine new H2O megamaser host galaxies to understand the flow of matter from kpc-scale galactic structures down to the supermassive black holes (SMBHs) at galactic centers. We double the sample analyzed in a similar way by Greene et al. and consider the properties of the combined sample of 18 sources. We find that disk-like structure is virtually ubiquitous when we can resolve hosts. We find marginal evidence that the disk-like nuclear structures show increasing misalignment from the kpc-scale host galaxy disk as the scale of the structure decreases. In turn, we find that the orientation of both the ˜100 pc scale nuclear structures and their host galaxy large-scale disks is consistent with random with respect to the orientation of their respective megamaser disks.

  2. Symbiont-mediated functions in insect hosts

    National Research Council Canada - National Science Library

    Su, Qi; Zhou, Xiaomao; Zhang, Youjun

    2013-01-01

    .... Bacterial symbionts play a prominent role in insect nutritional ecology by aiding in digestion of food or supplementing nutrients that insect hosts can't obtain sufficient amounts from a restricted diet of plant phloem...

  3. Mandatory Access Control applications to web hosting

    Science.gov (United States)

    Prandini, Marco; Faldella, Eugenio; Laschi, Roberto

    "Hosting" represents a commonplace solution for the low-cost implementation of web sites through the efficient sharing of the resources of a single server. The arising security problems, however, are not always easily dealt with under the Discretionary Access Control model implemented by traditional operating systems. More robust separation between the hosted sites, as well as more robust protection of the host system, can be attained by exploiting the features typical of Mandatory Access Control systems. Recently, these systems have recently been made available to the vast Linux community through projects like SELinux and grsecurity. This paper describes the architecture of a secure hosting server, integrating SELinux functionalities into the Apache/PHP platform, designed with the goal of increasing security without adding administrative burdens or impacting performance.

  4. Bridge hosts, a missing link for disease ecology in multi-host systems.

    Science.gov (United States)

    Caron, Alexandre; Cappelle, Julien; Cumming, Graeme S; de Garine-Wichatitsky, Michel; Gaidet, Nicolas

    2015-07-21

    In ecology, the grouping of species into functional groups has played a valuable role in simplifying ecological complexity. In epidemiology, further clarifications of epidemiological functions are needed: while host roles may be defined, they are often used loosely, partly because of a lack of clarity on the relationships between a host's function and its epidemiological role. Here we focus on the definition of bridge hosts and their epidemiological consequences. Bridge hosts provide a link through which pathogens can be transmitted from maintenance host populations or communities to receptive populations that people want to protect (i.e., target hosts). A bridge host should (1) be competent for the pathogen or able to mechanically transmit it; and (2) come into direct contact or share habitat with both maintenance and target populations. Demonstration of bridging requires an operational framework that integrates ecological and epidemiological approaches. We illustrate this framework using the example of the transmission of Avian Influenza Viruses across wild bird/poultry interfaces in Africa and discuss a range of other examples that demonstrate the usefulness of our definition for other multi-host systems. Bridge hosts can be particularly important for understanding and managing infectious disease dynamics in multi-host systems at wildlife/domestic/human interfaces, including emerging infections.

  5. Directional Selection from Host Plants Is a Major Force Driving Host Specificity in Magnaporthe Species.

    Science.gov (United States)

    Zhong, Zhenhui; Norvienyeku, Justice; Chen, Meilian; Bao, Jiandong; Lin, Lianyu; Chen, Liqiong; Lin, Yahong; Wu, Xiaoxian; Cai, Zena; Zhang, Qi; Lin, Xiaoye; Hong, Yonghe; Huang, Jun; Xu, Linghong; Zhang, Honghong; Chen, Long; Tang, Wei; Zheng, Huakun; Chen, Xiaofeng; Wang, Yanli; Lian, Bi; Zhang, Liangsheng; Tang, Haibao; Lu, Guodong; Ebbole, Daniel J; Wang, Baohua; Wang, Zonghua

    2016-05-06

    One major threat to global food security that requires immediate attention, is the increasing incidence of host shift and host expansion in growing number of pathogenic fungi and emergence of new pathogens. The threat is more alarming because, yield quality and quantity improvement efforts are encouraging the cultivation of uniform plants with low genetic diversity that are increasingly susceptible to emerging pathogens. However, the influence of host genome differentiation on pathogen genome differentiation and its contribution to emergence and adaptability is still obscure. Here, we compared genome sequence of 6 isolates of Magnaporthe species obtained from three different host plants. We demonstrated the evolutionary relationship between Magnaporthe species and the influence of host differentiation on pathogens. Phylogenetic analysis showed that evolution of pathogen directly corresponds with host divergence, suggesting that host-pathogen interaction has led to co-evolution. Furthermore, we identified an asymmetric selection pressure on Magnaporthe species. Oryza sativa-infecting isolates showed higher directional selection from host and subsequently tends to lower the genetic diversity in its genome. We concluded that, frequent gene loss or gain, new transposon acquisition and sequence divergence are host adaptability mechanisms for Magnaporthe species, and this coevolution processes is greatly driven by directional selection from host plants.

  6. Host reproductive phenology drives seasonal patterns of host use in mosquitoes.

    Directory of Open Access Journals (Sweden)

    Nathan D Burkett-Cadena

    2011-03-01

    Full Text Available Seasonal shifts in host use by mosquitoes from birds to mammals drive the timing and intensity of annual epidemics of mosquito-borne viruses, such as West Nile virus, in North America. The biological mechanism underlying these shifts has been a matter of debate, with hypotheses falling into two camps: (1 the shift is driven by changes in host abundance, or (2 the shift is driven by seasonal changes in the foraging behavior of mosquitoes. Here we explored the idea that seasonal changes in host use by mosquitoes are driven by temporal patterns of host reproduction. We investigated the relationship between seasonal patterns of host use by mosquitoes and host reproductive phenology by examining a seven-year dataset of blood meal identifications from a site in Tuskegee National Forest, Alabama USA and data on reproduction from the most commonly utilized endothermic (white-tailed deer, great blue heron, yellow-crowned night heron and ectothermic (frogs hosts. Our analysis revealed that feeding on each host peaked during periods of reproductive activity. Specifically, mosquitoes utilized herons in the spring and early summer, during periods of peak nest occupancy, whereas deer were fed upon most during the late summer and fall, the period corresponding to the peak in births for deer. For frogs, however, feeding on early- and late-season breeders paralleled peaks in male vocalization. We demonstrate for the first time that seasonal patterns of host use by mosquitoes track the reproductive phenology of the hosts. Peaks in relative mosquito feeding on each host during reproductive phases are likely the result of increased tolerance and decreased vigilance to attacking mosquitoes by nestlings and brooding adults (avian hosts, quiescent young (avian and mammalian hosts, and mate-seeking males (frogs.

  7. Mesoscale spatiotemporal variability in a complex host-parasite system influenced by intermediate host body size

    Directory of Open Access Journals (Sweden)

    Sara M. Rodríguez

    2017-08-01

    Full Text Available Background Parasites are essential components of natural communities, but the factors that generate skewed distributions of parasite occurrences and abundances across host populations are not well understood. Methods Here, we analyse at a seascape scale the spatiotemporal relationships of parasite exposure and host body-size with the proportion of infected hosts (i.e., prevalence and aggregation of parasite burden across ca. 150 km of the coast and over 22 months. We predicted that the effects of parasite exposure on prevalence and aggregation are dependent on host body-sizes. We used an indirect host-parasite interaction in which migratory seagulls, sandy-shore molecrabs, and an acanthocephalan worm constitute the definitive hosts, intermediate hosts, and endoparasite, respectively. In such complex systems, increments in the abundance of definitive hosts imply increments in intermediate hosts’ exposure to the parasite’s dispersive stages. Results Linear mixed-effects models showed a significant, albeit highly variable, positive relationship between seagull density and prevalence. This relationship was stronger for small (cephalothorax length >15 mm than large molecrabs (<15 mm. Independently of seagull density, large molecrabs carried significantly more parasites than small molecrabs. The analysis of the variance-to-mean ratio of per capita parasite burden showed no relationship between seagull density and mean parasite aggregation across host populations. However, the amount of unexplained variability in aggregation was strikingly higher in larger than smaller intermediate hosts. This unexplained variability was driven by a decrease in the mean-variance scaling in heavily infected large molecrabs. Conclusions These results show complex interdependencies between extrinsic and intrinsic population attributes on the structure of host-parasite interactions. We suggest that parasite accumulation—a characteristic of indirect host

  8. How foreign investment affects host countries

    OpenAIRE

    Blomstrom, Magnus; Kokko, Ari

    1997-01-01

    Foreign direct investment may promote economic development by helping to improve productivity growth and exports in the multinationals'host countries, the authors conclude, after reviewing the empirical evidence. But the exact relationship between foreign multinational corporations and their host economies seems to vary between industries and countries. Multinational corporations mainly enter industries where barriers to entry and concentration are relatively high, and at first they increase ...

  9. Data hosting infrastructure for primary biodiversity data

    Science.gov (United States)

    2011-01-01

    Background Today, an unprecedented volume of primary biodiversity data are being generated worldwide, yet significant amounts of these data have been and will continue to be lost after the conclusion of the projects tasked with collecting them. To get the most value out of these data it is imperative to seek a solution whereby these data are rescued, archived and made available to the biodiversity community. To this end, the biodiversity informatics community requires investment in processes and infrastructure to mitigate data loss and provide solutions for long-term hosting and sharing of biodiversity data. Discussion We review the current state of biodiversity data hosting and investigate the technological and sociological barriers to proper data management. We further explore the rescuing and re-hosting of legacy data, the state of existing toolsets and propose a future direction for the development of new discovery tools. We also explore the role of data standards and licensing in the context of data hosting and preservation. We provide five recommendations for the biodiversity community that will foster better data preservation and access: (1) encourage the community's use of data standards, (2) promote the public domain licensing of data, (3) establish a community of those involved in data hosting and archival, (4) establish hosting centers for biodiversity data, and (5) develop tools for data discovery. Conclusion The community's adoption of standards and development of tools to enable data discovery is essential to sustainable data preservation. Furthermore, the increased adoption of open content licensing, the establishment of data hosting infrastructure and the creation of a data hosting and archiving community are all necessary steps towards the community ensuring that data archival policies become standardized. PMID:22373257

  10. Ectoparasite reproductive performance when host condition varies.

    Science.gov (United States)

    Rueesch, Shona; Lemoine, Mélissa; Richner, Heinz

    2012-09-01

    Host condition can influence both the nutritive resources available to parasites and the strength of host defences. Since these factors are likely to be correlated, it is unclear whether parasites would be more successful on hosts in good, intermediate or poor conditions. For more complex parasites, like fleas, where larvae depend on adults to extract and make available some essential host resources, host condition can act at two levels. First, it can affect the investment of females into eggs, and second, it can influence offspring growth. In a two-step experiment, we first let female hen fleas Ceratophyllus gallinae feed on nestlings of reduced, control or enlarged great tit Parus major broods and secondly used the blood from these nestlings as a food source for flea larvae reared in the laboratory. We then assessed the effect of brood size manipulation on reproductive investment and survival of female fleas, and on survival, developmental time, mass and size of pre-imago larvae and adults of the first generation. Although host condition, measured as body mass controlled for body size, was significantly influenced by brood size manipulation, it did not affect the female fleas' reproductive investment and survival. Larvae fed with blood from nestlings of reduced broods lived longer, however, than larvae fed on blood from enlarged or control broods. Additionally, F1 adults grew shorter tibiae when their mother had fed on hosts of reduced broods. The finding that brood size manipulation influenced parasite reproduction suggests that it affected nutritive resources and/or host defence, but the precise mechanism or balance between the two requires further investigation.

  11. Host Proteome Research in HIV Infection

    OpenAIRE

    Zhang, Lijun; Zhang, Xiaojun; Ma, Qing; Zhou, Honghao

    2010-01-01

    Proteomics has been widely used in the last few years to look for new biomarkers and decipher the mechanism of HIV?host interaction. Herein, we review the recent developments of HIV/AIDS proteomic research, including the samples used in HIV/AIDS related research, the technologies used for proteomic study, the diagnosis biomarkers of HIV-associated disease especially HIV-associated neurocognitive impairment, the mechanisms of HIV?host interaction, HIV-associated dementia, substance abuse, and ...

  12. The allometry of host-pathogen interactions.

    Directory of Open Access Journals (Sweden)

    Jessica M Cable

    2007-11-01

    Full Text Available Understanding the mechanisms that control rates of disease progression in humans and other species is an important area of research relevant to epidemiology and to translating studies in small laboratory animals to humans. Body size and metabolic rate influence a great number of biological rates and times. We hypothesize that body size and metabolic rate affect rates of pathogenesis, specifically the times between infection and first symptoms or death.We conducted a literature search to find estimates of the time from infection to first symptoms (t(S and to death (t(D for five pathogens infecting a variety of bird and mammal hosts. A broad sampling of diseases (1 bacterial, 1 prion, 3 viruses indicates that pathogenesis is controlled by the scaling of host metabolism. We find that the time for symptoms to appear is a constant fraction of time to death in all but one disease. Our findings also predict that many population-level attributes of disease dynamics are likely to be expressed as dimensionless quantities that are independent of host body size.Our results show that much variability in host pathogenesis can be described by simple power functions consistent with the scaling of host metabolic rate. Assessing how disease progression is controlled by geometric relationships will be important for future research. To our knowledge this is the first study to report the allometric scaling of host/pathogen interactions.

  13. Host immune responses accelerate pathogen evolution.

    Science.gov (United States)

    Trivedi, Pankaj; Wang, Nian

    2014-03-01

    Pathogens face a hostile and often novel environment when infecting a new host, and adaptation is likely to be an important determinant of the success in colonization and establishment. We hypothesized that resistant hosts will impose stronger selection on pathogens than susceptible hosts, which should accelerate pathogen evolution through selection biased toward effector genes. To test this hypothesis, we conducted an experimental evolution study on Xanthomonas citri subsp. citri (Xcc) in a susceptible plant species and a resistant plant species. We performed 55 rounds of repeated reinoculation of Xcc through susceptible host grapefruit (isolates G1, G2, G3) and resistant host kumquat (isolates K1, K2, K3). Consequently, only K1 and K3 isolates lost their ability to elicit a hypersensitive response (HR) in kumquat. Illumina sequencing of the parental and descendant strains P, G1, G2, G3, K1, K2 and K3 revealed that fixed mutations were biased toward type three secretion system effectors in isolates K1 and K3. Parallel evolution was observed in the K1 and K3 strains, suggesting that the mutations result from selection rather than by random drift. Our results support our hypothesis and suggest that repeated infection of resistant hosts by pathogens should be prevented to avoid selecting for adaptive pathogens.

  14. The current Salmonella–host interactome

    Science.gov (United States)

    Schleker, Sylvia; Sun, Jingchun; Raghavan, Balachandran; Srnec, Matthew; Müller, Nicole; Koepfinger, Mary; Murthy, Leelavati; Zhao, Zhongming; Klein-Seetharaman, Judith

    2011-01-01

    Salmonella bacteria cause millions of infections and thousands of deaths every year. This pathogen has an unusually broad host range including humans, animals, and even plants. During infection, Salmonella expresses a variety of virulence factors and effectors that are delivered into the host cell triggering cellular responses through protein–protein interactions (PPIs) with host cell proteins which make the pathogen’s invasion and replication possible. To speed up proteomic efforts in elucidating Salmonella–host interactomes, we carried out a survey of the currently published Salmonella–host PPI. Such a list can serve as the gold standard for computational models aimed at predicting Salmonella–host interactomes through integration of large-scale biological data sources. Manual literature and database search of >2200 journal articles and >100 databases resulted in a gold standard list of currently 62 PPI, including primarily interactions of Salmonella proteins with human and mouse proteins. Only six of these interactions were directly retrievable from PPI databases and 16 were highlighted in databases featuring literature extracts. Thus, the literature survey resulted in the most complete interactome available to date for Salmonella. Pathway analysis using Ingenuity and Broad Gene Set Enrichment Analysis (GSEA) software revealed among general pathways such as MAPK signaling in particular those related to cell death as well as cell morphology, turnover, and interactions, in addition to response to not only Salmonella but also other pathogenic – viral and bacterial – infections. The list of interactions is available at http://www.shiprec.org/indicationslist.htm PMID:22213674

  15. Sumoylation at the Host-Pathogen Interface

    Directory of Open Access Journals (Sweden)

    Van G. Wilson

    2012-04-01

    Full Text Available Many viral proteins have been shown to be sumoylated with corresponding regulatory effects on their protein function, indicating that this host cell modification process is widely exploited by viral pathogens to control viral activity. In addition to using sumoylation to regulate their own proteins, several viral pathogens have been shown to modulate overall host sumoylation levels. Given the large number of cellular targets for SUMO addition and the breadth of critical cellular processes that are regulated via sumoylation, viral modulation of overall sumoylation presumably alters the cellular environment to ensure that it is favorable for viral reproduction and/or persistence. Like some viruses, certain bacterial plant pathogens also target the sumoylation system, usually decreasing sumoylation to disrupt host anti-pathogen responses. The recent demonstration that Listeria monocytogenes also disrupts host sumoylation, and that this is required for efficient infection, extends the plant pathogen observations to a human pathogen and suggests that pathogen modulation of host sumoylation may be more widespread than previously appreciated. This review will focus on recent aspects of how pathogens modulate the host sumoylation system and how this benefits the pathogen.

  16. The Potential for Hosted Payloads at NASA

    Science.gov (United States)

    Andraschko, Mark; Antol, Jeffrey; Baize, Rosemary; Horan, Stephen; Neil, Doreen; Rinsland, Pamela; Zaiceva, Rita

    2012-01-01

    The 2010 National Space Policy encourages federal agencies to actively explore the use of inventive, nontraditional arrangements for acquiring commercial space goods and services to meet United States Government requirements, including...hosting government capabilities on commercial spacecraft. NASA's Science Mission Directorate has taken an important step towards this goal by adding an option for hosted payload responses to its recent Announcement of Opportunity (AO) for Earth Venture-2 missions. Since NASA selects a significant portion of its science missions through a competitive process, it is useful to understand the implications that this process has on the feasibility of successfully proposing a commercially hosted payload mission. This paper describes some of the impediments associated with proposing a hosted payload mission to NASA, and offers suggestions on how these impediments might be addressed. Commercially hosted payloads provide a novel way to serve the needs of the science and technology demonstration communities at a fraction of the cost of a traditional Geostationary Earth Orbit (GEO) mission. The commercial communications industry launches over 20 satellites to GEO each year. By exercising this repeatable commercial paradigm of privately financed access to space with proven vendors, NASA can achieve science goals at a significantly lower cost than the current dedicated spacecraft and launch vehicle approach affords. Commercial hosting could open up a new realm of opportunities for NASA science missions to make measurements from GEO. This paper also briefly describes two GEO missions recommended by the National Academies of Science Earth Science Decadal Survey, the Geostationary Coastal and Air Pollution Events (GEO-CAPE) mission and the Precipitation and All-weather Temperature and Humidity (PATH) mission. Hosted payload missions recently selected for implementation by the Office of the Chief Technologist are also discussed. Finally, there are

  17. Host-to-Host Transmission of the Pneumococcus-New Victims of a Toxic Relationship.

    Science.gov (United States)

    Trappetti, Claudia; Paton, James C

    2017-01-11

    Host-to-host transmission is critical for survival of the human-adapted bacterium Streptococcus pneumoniae. In this issue of Cell Host & Microbe, Zafar et al. (2017) show that transmission is dependent on nasopharyngeal inflammation elicited by the toxin pneumolysin, causing increased shedding and enhanced survival of the bacterium in the environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Local host adaptation and use of a novel host in the seed beetle Megacerus eulophus.

    Directory of Open Access Journals (Sweden)

    Gisela C Stotz

    Full Text Available Spatial variation in host plant availability may lead to specialization in host use and local host adaptation in herbivorous insects, which may involve a cost in performance on other hosts. We studied two geographically separated populations of the seed beetle Megacerus eulophus (Coleoptera: Bruchidae in central Chile: a population from the host Convolvulus chilensis (in Aucó and a population from C. bonariensis (in Algarrobo. In Aucó C. chilensis is the only host plant, while in Algarrobo both C. bonariensis and C. chilensis are available. We tested local adaptation to these native host plants and its influence on the use of another, exotic host plant. We hypothesized that local adaptation would be verified, particularly for the one-host population (Aucó, and that the Aucó population would be less able to use an alternative, high-quality host. We found evidence of local adaptation in the population from C. chilensis. Thus, when reared on C. chilensis, adults from the C. chilensis population were larger and lived longer than individuals from the C. bonariensis population, while bruchids from the two populations had the same body size and longevity when reared on C. bonariensis. Overall, bruchids from the C. chilensis population showed greater performance traits than those from the C. bonariensis population. There were no differences between the bruchid populations in their ability to use the alternative, exotic host Calystegia sepium, as shown by body size and longevity patterns. Results suggest that differences in local adaptation might be explained by differential host availability in the study populations.

  19. Divergence in Olfactory Host Plant Preference in D. mojavensis in Response to Cactus Host Use

    OpenAIRE

    Priya Date; Dweck, Hany K. M.; Stensmyr, Marcus C; Jodi Shann; Hansson, Bill S.; Rollmann, Stephanie M.

    2013-01-01

    Divergence in host adaptive traits has been well studied from an ecological and evolutionary perspective, but identification of the proximate mechanisms underlying such divergence is less well understood. Behavioral preferences for host plants are often mediated by olfaction and shifts in preference may be accompanied by changes in the olfactory system. In this study, we examine the evolution of host plant preferences in cactophilic Drosophila mojavensis that feeds and breeds on different cac...

  20. Animal salmonelloses: a brief review of “host adaptation and host specificity” of Salmonella spp.

    Directory of Open Access Journals (Sweden)

    Grammato Evangelopoulou

    2013-07-01

    Full Text Available Salmonella enterica, the most pathogenic species of the genusSalmonella, includes more than 2,500 serovars, many of which are of great veterinary and medical significance. The emergence of food-borne pathogens, such as Salmonella spp., has increased knowledge about the mechanisms helping microorganisms to persist and spread within new host populations. It has also increased information about the properties they acquire for adapting in the biological environment of a new host. Thedifferences observed between serovars in their host preference and clinical manifestations are referred to as “serovar-host specificity” or “serovar-host adaptation”. The genus Salmonella, highly adaptive to vertebrate hosts, has many pathogenic serovars showing host specificity. Serovar Salmonella Typhi, causing disease to man and higher primates, is a good example of host specificity. Thus, understanding the mechanisms that Salmonella serovars use to overcome animal species' barriers or adapt to new hosts is also important for understanding the origins of any other infectious diseases or the emergence of new pathogens. In addition, molecular methods used to study the virulence determinants of Salmonella serovars, could also be used to model ways of studying the virulence determinants used by bacteria in general, when causing disease to a specific animal species

  1. HOST PLANT UTILIZATION, HOST RANGE OSCILLATIONS AND DIVERSIFICATION IN NYMPHALID BUTTERFLIES: A PHYLOGENETIC INVESTIGATION

    Science.gov (United States)

    Nylin, Sören; Slove, Jessica; Janz, Niklas

    2014-01-01

    It has been suggested that phenotypic plasticity is a major factor in the diversification of life, and that variation in host range in phytophagous insects is a good model for investigating this claim. We explore the use of angiosperm plants as hosts for nymphalid butterflies, and in particular the evidence for past oscillations in host range and how they are linked to host shifts and to diversification. At the level of orders of plants, a relatively simple pattern of host use and host shifts emerges, despite the 100 million years of history of the family Nymphalidae. We review the evidence that these host shifts and the accompanying diversifications were associated with transient polyphagous stages, as suggested by the “oscillation hypothesis.” In addition, we investigate all currently polyphagous nymphalid species and demonstrate that the state of polyphagy is rare, has a weak phylogenetic signal, and a very apical distribution in the phylogeny; we argue that these are signs of its transient nature. We contrast our results with data from the bark beetles Dendroctonus, in which a more specialized host use is instead the apical state. We conclude that plasticity in host use is likely to have contributed to diversification in nymphalid butterflies. PMID:24372598

  2. A parasite's modification of host behavior reduces predation on its host.

    Science.gov (United States)

    Soghigian, John; Valsdottir, Linda R; Livdahl, Todd P

    2017-03-01

    Parasite modification of host behavior is common, and the literature is dominated by demonstrations of enhanced predation on parasitized prey resulting in transmission of parasites to their next host. We present a case in which predation on parasitized prey is reduced. Despite theoretical modeling suggesting that this phenomenon should be common, it has been reported in only a few host-parasite-predator systems. Using a system of gregarine endosymbionts in host mosquitoes, we designed experiments to compare the vulnerability of parasitized and unparasitized mosquito larvae to predation by obligate predatory mosquito larvae and then compared behavioral features known to change in the presence of predatory cues. We exposed Aedes triseriatus larvae to the parasite Ascogregarina barretti and the predator Toxohrynchites rutilus and assessed larval mortality rate under each treatment condition. Further, we assessed behavioral differences in larvae due to infection and predation stimuli by recording larvae and scoring behaviors and positions within microcosms. Infection with gregarines reduced cohort mortality in the presence of the predator, but the parasite did not affect mortality alone. Further, infection by parasites altered behavior such that infected hosts thrashed less frequently than uninfected hosts and were found more frequently on or in a refuge within the microcosm. By reducing predation on their host, gregarines may be acting as mutualists in the presence of predation on their hosts. These results illustrate a higher-order interaction, in which a relationship between a species pair (host-endosymbiont or predator-prey) is altered by the presence of a third species.

  3. Adaptation to different host plant ages facilitates insect divergence without a host shift.

    Science.gov (United States)

    Zhang, Bin; Segraves, Kari A; Xue, Huai-Jun; Nie, Rui-E; Li, Wen-Zhu; Yang, Xing-Ke

    2015-09-22

    Host shifts and subsequent adaption to novel host plants are important drivers of speciation among phytophagous insects. However, there is considerably less evidence for host plant-mediated speciation in the absence of a host shift. Here, we investigated divergence of two sympatric sister elm leaf beetles, Pyrrhalta maculicollis and P. aenescens, which feed on different age classes of the elm Ulmus pumila L. (seedling versus adult trees). Using a field survey coupled with preference and performance trials, we show that these beetle species are highly divergent in both feeding and oviposition preference and specialize on either seedling or adult stages of their host plant. An experiment using artificial leaf discs painted with leaf surface wax extracts showed that host plant chemistry is a critical element that shapes preference. Specialization appears to be driven by adaptive divergence as there was also evidence of divergent selection; beetles had significantly higher survival and fecundity when reared on their natal host plant age class. Together, the results identify the first probable example of divergence induced by host plant age, thus extending how phytophagous insects might diversify in the absence of host shifts. © 2015 The Author(s).

  4. Are cryptic host species also cryptic to parasites? Host specificity and geographical distribution of acanthocephalan parasites infecting freshwater Gammarus

    OpenAIRE

    Westram A. M.; Baumgartner C; Keller I; Jokela J.

    2011-01-01

    Many parasites infect multiple host species. In coevolving host parasite interactions theory predicts that parasites should be adapted to locally common hosts which could lead to regional shifts in host preferences. We studied the interaction between freshwater Gammarus (Crustacea Amphipoda) and their acanthocephalan parasites using a large scale field survey and experiments combined with molecular identification of cryptic host and parasite species. Gammarus pulex is a common host for multip...

  5. Deconstructing host-pathogen interactions in Drosophila

    Science.gov (United States)

    Bier, Ethan; Guichard, Annabel

    2012-01-01

    Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host. PMID:21979942

  6. Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations.

    Science.gov (United States)

    Thaiss, Christoph A; Levy, Maayan; Korem, Tal; Dohnalová, Lenka; Shapiro, Hagit; Jaitin, Diego A; David, Eyal; Winter, Deborah R; Gury-BenAri, Meital; Tatirovsky, Evgeny; Tuganbaev, Timur; Federici, Sara; Zmora, Niv; Zeevi, David; Dori-Bachash, Mally; Pevsner-Fischer, Meirav; Kartvelishvily, Elena; Brandis, Alexander; Harmelin, Alon; Shibolet, Oren; Halpern, Zamir; Honda, Kenya; Amit, Ido; Segal, Eran; Elinav, Eran

    2016-12-01

    The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day. This diurnal microbial behavior drives, in turn, the global programming of the host circadian transcriptional, epigenetic, and metabolite oscillations. Surprisingly, disruption of homeostatic microbiome rhythmicity not only abrogates normal chromatin and transcriptional oscillations of the host, but also incites genome-wide de novo oscillations in both intestine and liver, thereby impacting diurnal fluctuations of host physiology and disease susceptibility. As such, the rhythmic biogeography and metabolome of the intestinal microbiota regulates the temporal organization and functional outcome of host transcriptional and epigenetic programs. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The host galaxy of GRB 990712

    DEFF Research Database (Denmark)

    Christensen, L.; Hjorth, J.; Gorosabel, J.

    2004-01-01

    galaxy types shows that the host is similar to a moderately kreddened starburst galaxy with a young stellar population. The estimated internal extinction in the host is A(V) = 0.15 +/- 0.1 and the star-formation rate (SFR) from the UV continuum is 1.3 +/- 0.3 M-circle dot yr(-1) (not corrected......We present a comprehensive study of the z = 0.43 host galaxy of GRB 990712, involving ground-based photometry, spectroscopy, and HST imaging. The broad-band UBVRIJHKs photometry is used to determine the global spectral energy distribution (SED) of the host galaxy. Comparison with that of known...... for the effects of extinction). Other galaxy template spectra than starbursts failed to reproduce the observed SED. We also present VLT spectra leading to the detection of Halpha from the GRB host galaxy. A SFR of 2.8 +/- 0.7 M-circle dot yr(-1) is inferred from the Halpha line flux, and the presence of a young...

  8. Proteinaceous Molecules Mediating Bifidobacterium-Host Interactions

    Science.gov (United States)

    Ruiz, Lorena; Delgado, Susana; Ruas-Madiedo, Patricia; Margolles, Abelardo; Sánchez, Borja

    2016-01-01

    Bifidobacteria are commensal microoganisms found in the gastrointestinal tract. Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics, and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization, or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota, and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs. PMID:27536282

  9. Early-season host switching in Adelphocoris spp. (Hemiptera: Miridae of differing host breadth.

    Directory of Open Access Journals (Sweden)

    Hongsheng Pan

    Full Text Available The mirid bugs Adelphocoris suturalis (Jakovlev, Adelphocoris lineolatus (Goeze and Adelphocoris fasciaticollis (Reuter (Hemiptera: Miridae are common pests of several agricultural crops. These three species have vastly different geographical distributions, phenologies and abundances, all of which are linked to their reliance on local plants. Previous work has shown notable differences in Adelphocoris spp. host use for overwintering. In this study, we assessed the extent to which each of the Adelphocoris spp. relies on some of its major overwinter hosts for spring development. Over the course of four consecutive years (2009-2012, we conducted population surveys on 77 different plant species from 39 families. During the spring, A. fasciaticollis used the broadest range of hosts, as it was found on 35 plant species, followed by A. suturalis (15 species and A. lineolatus (7 species. Abundances of the species greatly differed between host plants, with A. fasciaticollis reaching the highest abundance on Chinese date (Ziziphus jujuba Mill., whereas both A. suturalis and A. lineolatus preferred alfalfa (Medicago sativa L.. The host breadths of the three Adelphocoris spp. differed greatly between subsequent spring and winter seasons. The generalist species exhibited the least host fidelity, with A. suturalis and A. lineolatus using 8 of 22 and 4 of 12 overwinter host species for spring development, respectively. By contrast, the comparative specialist A. fasciaticollis relied on 9 of its 11 overwinter plants as early-season hosts. We highlight important seasonal changes in host breadth and interspecific differences in the extent of host switching behavior between the winter and spring seasons. These findings benefit our understanding of the evolutionary interactions between mirid bugs and their host plants and can be used to guide early-season population management.

  10. Plants as alternative hosts for Salmonella.

    Science.gov (United States)

    Schikora, Adam; Garcia, Ana V; Hirt, Heribert

    2012-05-01

    Recent findings show that many human pathogenic bacteria can use multiple host organisms. For example, Salmonella Typhimurium can use plants as alternative hosts to humans and other animals. These bacteria are able to adhere to plant surfaces and actively infect the interior of plants. Similarly to the infection of animal cells, S. Typhimurium suppresses plant defense responses by a type III secretion mechanism, indicating that these bacteria possess a dedicated multi-kingdom infection strategy, raising the question of host specificity. In addition, evidence is accumulating that the interaction of Salmonella with plants is an active process with different levels of specificity, because different Salmonella serovars show variations in pathogenicity, and different plant species reveal various levels of resistance towards these bacteria. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Staphylococcus aureus pathogenesis in diverse host environments

    Science.gov (United States)

    Balasubramanian, Divya; Harper, Lamia; Shopsin, Bo; Torres, Victor J.

    2017-01-01

    Abstract Staphylococcus aureus is an eminent human pathogen that can colonize the human host and cause severe life-threatening illnesses. This bacterium can reside in and infect a wide range of host tissues, ranging from superficial surfaces like the skin to deeper tissues such as in the gastrointestinal tract, heart and bones. Due to its multifaceted lifestyle, S. aureus uses complex regulatory networks to sense diverse signals that enable it to adapt to different environments and modulate virulence. In this minireview, we explore well-characterized environmental and host cues that S. aureus responds to and describe how this pathogen modulates virulence in response to these signals. Lastly, we highlight therapeutic approaches undertaken by several groups to inhibit both signaling and the cognate regulators that sense and transmit these signals downstream. PMID:28104617

  12. New Hosts of The Lassa Virus.

    Science.gov (United States)

    Olayemi, Ayodeji; Cadar, Daniel; Magassouba, N'Faly; Obadare, Adeoba; Kourouma, Fode; Oyeyiola, Akinlabi; Fasogbon, Samuel; Igbokwe, Joseph; Rieger, Toni; Bockholt, Sabrina; Jérôme, Hanna; Schmidt-Chanasit, Jonas; Garigliany, Mutien; Lorenzen, Stephan; Igbahenah, Felix; Fichet, Jean-Nicolas; Ortsega, Daniel; Omilabu, Sunday; Günther, Stephan; Fichet-Calvet, Elisabeth

    2016-05-03

    Lassa virus (LASV) causes a deadly haemorrhagic fever in humans, killing several thousand people in West Africa annually. For 40 years, the Natal multimammate rat, Mastomys natalensis, has been assumed to be the sole host of LASV. We found evidence that LASV is also hosted by other rodent species: the African wood mouse Hylomyscus pamfi in Nigeria, and the Guinea multimammate mouse Mastomys erythroleucus in both Nigeria and Guinea. Virus strains from these animals were isolated in the BSL-4 laboratory and fully sequenced. Phylogenetic analyses of viral genes coding for glycoprotein, nucleoprotein, polymerase and matrix protein show that Lassa strains detected in M. erythroleucus belong to lineages III and IV. The strain from H. pamfi clusters close to lineage I (for S gene) and between II &III (for L gene). Discovery of new rodent hosts has implications for LASV evolution and its spread into new areas within West Africa.

  13. HCV genetic heterogeneity and its host genetics

    Directory of Open Access Journals (Sweden)

    NIE Yonghong

    2013-10-01

    Full Text Available Hepatitis C represents a major worldwide public health problem. Studies have shown that both genetic diversity of hepatitis C virus (HCV and genetic polymorphisms of IL-28B, ITPA, and IP-10 in the host are implicated in the progression of hepatitis C, treatment response, and adverse effects. The research advances in the molecular epidemiology and clinical and therapeutic interventions of HCV genetic heterogeneity and single nucleotide polymorphisms in its host are reviewed. It is suggested that there is a pressing need for reliable data on the molecular epidemiology of HCV and its host, which will assist in the decision making of public health issues and reduce the morbidity and mortality of hepatitis C worldwide.

  14. 5-(Perylen-3-yl)ethynyl-arabino-uridine (aUY11), an arabino-based rigid amphipathic fusion inhibitor, targets virion envelope lipids to inhibit fusion of influenza virus, hepatitis C virus, and other enveloped viruses.

    Science.gov (United States)

    Colpitts, Che C; Ustinov, Alexey V; Epand, Raquel F; Epand, Richard M; Korshun, Vladimir A; Schang, Luis M

    2013-04-01

    Entry of enveloped viruses requires fusion of viral and cellular membranes. Fusion requires the formation of an intermediate stalk structure, in which only the outer leaflets are fused. The stalk structure, in turn, requires the lipid bilayer of the envelope to bend into negative curvature. This process is inhibited by enrichment in the outer leaflet of lipids with larger polar headgroups, which favor positive curvature. Accordingly, phospholipids with such shape inhibit viral fusion. We previously identified a compound, 5-(perylen-3-yl)ethynyl-2'-deoxy-uridine (dUY11), with overall shape and amphipathicity similar to those of these phospholipids. dUY11 inhibited the formation of the negative curvature necessary for stalk formation and the fusion of a model enveloped virus, vesicular stomatitis virus (VSV). We proposed that dUY11 acted by biophysical mechanisms as a result of its shape and amphipathicity. To test this model, we have now characterized the mechanisms against influenza virus and HCV of 5-(perylen-3-yl)ethynyl-arabino-uridine (aUY11), which has shape and amphipathicity similar to those of dUY11 but contains an arabino-nucleoside. aUY11 interacted with envelope lipids to inhibit the infectivity of influenza virus, hepatitis C virus (HCV), herpes simplex virus 1 and 2 (HSV-1/2), and other enveloped viruses. It specifically inhibited the fusion of influenza virus, HCV, VSV, and even protein-free liposomes to cells. Furthermore, aUY11 inhibited the formation of negative curvature in model lipid bilayers. In summary, the arabino-derived aUY11 and the deoxy-derived dUY11 act by the same antiviral mechanisms against several enveloped but otherwise unrelated viruses. Therefore, chemically unrelated compounds of appropriate shape and amphipathicity target virion envelope lipids to inhibit formation of the negative curvature required for fusion, inhibiting infectivity by biophysical, not biochemical, mechanisms.

  15. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

    Science.gov (United States)

    Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B

    2016-04-02

    Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

  16. Safety, immunogenicity, and lot-to-lot consistency of a split-virion quadrivalent influenza vaccine in younger and older adults: a phase III randomized, double-blind clinical trial.

    Science.gov (United States)

    Sesay, Sanie; Brzostek, Jerzy; Meyer, Ingo; Donazzolo, Yves; Leroux-Roels, Geert; Rouzier, Régine; Astruc, Béatrice; Szymanski, Henryk; Toursarkissian, Nicole; Vandermeulen, Corinne; Kowalska, Edyta; Van Damme, Pierre; Salamand, Camille; Pepin, Stephanie

    2017-10-02

    Here, we report a randomized multicenter phase III trial assessing the lot-to-lot consistency of the 2014-2015 Northern Hemisphere quadrivalent split-virion inactivated influenza vaccine (IIV4; Sanofi Pasteur) and comparing its immunogenicity and safety with that of trivalent inactivated influenza vaccine (IIV3) in younger and older adults (EudraCT no. 2014-000785-21). Younger (18-60 y, n = 1114) and older (>60 y, n = 1111) adults were randomized 2:2:2:1:1 to receive a single dose of one of three lots of IIV4, the licensed IIV3 containing the B Yamagata lineage strain, or an investigational IIV3 containing the B Victoria lineage strain. Post-vaccination (day 21) hemagglutination inhibition antibody titers were equivalent for the three IIV4 lots. For the pooled IIV4s vs. IIV3, hemagglutination inhibition antibody titers were also non-inferior for the A strains, non-inferior for the B strain when present in the comparator IIV3, and superior for the B strain lineage when absent from the comparator IIV3. For all vaccine strains, seroprotection rates were ≥98% in younger adults and ≥90% in older adults. IIV4 also increased seroneutralizing antibody titers against all three vaccine strains of influenza. All vaccines were well tolerated, with no safety concerns identified. Solicited injection-site reactions were similar for IIV4 and IIV3 and mostly grade 1 and transient. This study showed that in younger and older adults, IIV4 had a similar safety profile as the licensed IIV3 and that including a second B strain lineage in IIV4 provided superior immunogenicity for the added B strain without affecting the immunogenicity of the three IIV3 strains.

  17. Lymphadenectomy prior to rat hind limb allotransplantation prevents graft-versus-host disease in chimeric hosts

    NARCIS (Netherlands)

    Brouha, PCR; Perez-Abadia, G; Francois, CG; Laurentin-Perez, LA; Gorantla, [No Value; Vossen, M; Tai, C; Pidwell, D; Anderson, GL; Stadelmann, WK; Hewitt, CW; Kon, M; Barker, JH; Maldonado, C

    In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if immunocompetent cells in bone marrow (BM) and/or lymph nodes (LNs) of

  18. Wolbachia-Host Interactions: Host Mating Patterns Affect Wolbachia Density Dynamics.

    Directory of Open Access Journals (Sweden)

    Dong-Xiao Zhao

    Full Text Available Wolbachia are maternally inherited intracellular bacteria that infect a wide range of arthropods and cause an array of effects on host reproduction, fitness and mating behavior. Although our understanding of the Wolbachia-associated effects on hosts is rapidly expanding, our knowledge of the host factors that mediate Wolbachia dynamics is rudimentary. Here, we explore the interactions between Wolbachia and its host, the two-spotted spider mite Tetranychus urticae Koch. Our results indicate that Wolbachia induces strong cytoplasmic incompatibility (CI, increases host fecundity, but has no effects on the longevity of females and the mating competitiveness of males in T. urticae. Most importantly, host mating pattern was found to affect Wolbachia density dynamics during host aging. Mating of an uninfected mite of either sex with an infected mite attenuates the Wolbachia density in the infected mite. According to the results of Wolbachia localization, this finding may be associated with the tropism of Wolbachia for the reproductive tissue in adult spider mites. Our findings describe a new interaction between Wolbachia and their hosts.

  19. Preference of diamondback moth larvae for novel and original host plant after host range expansion

    NARCIS (Netherlands)

    Henniges-Janssen, K.; Heckel, D.G.; Groot, A.T.

    2014-01-01

    Utilization of a novel plant host by herbivorous insects requires coordination of numerous physiological and behavioral adaptations in both larvae and adults. The recent host range expansion of the crucifer-specialist diamondback moth (DBM), Plutella xylostella L. (Lepidoptera: Plutellidae), to the

  20. Host-age discrimination during host location by Cotesia glomerata, a larval parasitoid of Pieris brassicae.

    NARCIS (Netherlands)

    Mattiacci, L.; Dicke, M.

    1995-01-01

    Some parasitoids are restricted with respect to the host stage that they attack and even to a certain age within a stage. In this paper we investigate whether the parasitoid Cotesia glomerata can discriminate between old and young caterpillar instars of its host, Pieris brassicae, before contacting

  1. Monkeypox Virus Host Factor Screen Using Haploid Cells Identifies Essential Role of GARP Complex in Extracellular Virus Formation.

    Science.gov (United States)

    Realegeno, Susan; Puschnik, Andreas S; Kumar, Amrita; Goldsmith, Cynthia; Burgado, Jillybeth; Sambhara, Suryaprakash; Olson, Victoria A; Carroll, Darin; Damon, Inger; Hirata, Tetsuya; Kinoshita, Taroh; Carette, Jan E; Satheshkumar, Panayampalli Subbian

    2017-06-01

    Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. We validated the role of a set of vacuolar protein sorting (VPS) genes during infection, VPS51 to VPS54 (VPS51-54), which comprise the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex involved in retrograde transport of endosomes to the trans -Golgi apparatus. Our data demonstrate that VPS52 and VPS54 were dispensable for mature virion (MV) production but were required for extracellular virus (EV) formation. For comparison, a known antiviral compound, ST-246, was used in our experiments, demonstrating that EV titers in VPS52 and VPS54 knockout (KO) cells were comparable to levels exhibited by ST-246-treated wild-type cells. Confocal microscopy was used to examine actin tail formation, one of the viral egress mechanisms for cell-to-cell dissemination, and revealed an absence of actin tails in VPS52KO- or VPS54KO-infected cells. Further evaluation of these cells by electron microscopy demonstrated a decrease in levels of wrapped viruses (WVs) compared to those seen with the wild-type control. Collectively, our data demonstrate the role of GARP complex genes in double-membrane wrapping of MVs necessary for EV formation, implicating the host endosomal trafficking pathway in orthopoxvirus infection. IMPORTANCE Human monkeypox is an emerging zoonotic infectious disease caused by Monkeypox virus (MPXV). Of the two MPXV clades, the Congo Basin strain is associated with severe

  2. Morphology of methane hydrate host sediments

    Science.gov (United States)

    Jones, K.W.; Feng, H.; Tomov, S.; Winters, W.J.; Eaton, M.; Mahajan, D.

    2005-01-01

    The morphological features including porosity and grains of methane hydrate host sediments were investigated using synchrotron computed microtomography (CMT) technique. The sediment sample was obtained during Ocean Drilling Program Leg 164 on the Blake Ridge at water depth of 2278.5 m. The CMT experiment was performed at the Brookhaven National Synchrotron Light Source facility. The analysis gave ample porosity, specific surface area, mean particle size, and tortuosity. The method was found to be highly effective for the study of methane hydrate host sediments.

  3. Manipulative parasites may not alter intermediate host distribution but still enhance their transmission: field evidence for increased vulnerability to definitive hosts and non-host predator avoidance.

    Science.gov (United States)

    Lagrue, C; Güvenatam, A; Bollache, L

    2013-02-01

    Behavioural alterations induced by parasites in their intermediate hosts can spatially structure host populations, possibly resulting in enhanced trophic transmission to definitive hosts. However, such alterations may also increase intermediate host vulnerability to non-host predators. Parasite-induced behavioural alterations may thus vary between parasite species and depend on each parasite definitive host species. We studied the influence of infection with 2 acanthocephalan parasites (Echinorhynchus truttae and Polymorphus minutus) on the distribution of the amphipod Gammarus pulex in the field. Predator presence or absence and predator species, whether suitable definitive host or dead-end predator, had no effect on the micro-distribution of infected or uninfected G. pulex amphipods. Although neither parasite species seem to influence intermediate host distribution, E. truttae infected G. pulex were still significantly more vulnerable to predation by fish (Cottus gobio), the parasite's definitive hosts. In contrast, G. pulex infected with P. minutus, a bird acanthocephalan, did not suffer from increased predation by C. gobio, a predator unsuitable as host for P. minutus. These results suggest that effects of behavioural changes associated with parasite infections might not be detectable until intermediate hosts actually come in contact with predators. However, parasite-induced changes in host spatial distribution may still be adaptive if they drive hosts into areas of high transmission probabilities.

  4. Modeling within-host HIV-1 dynamics and the evolution of drug resistance: trade-offs between viral enzyme function and drug susceptibility

    Science.gov (United States)

    Rong, Libin; Gilchrist, Michael A.; Feng, Zhilan; Perelson, Alan S.

    2007-01-01

    There are many biological steps between viral infection of CD4+ T cells and the production of HIV-1 virions. Here we incorporate an eclipse phase, representing the stage in which infected T cells have not started to produce new virus, into a simple HIV-1 model. Model calculations suggest that the quicker infected T cells progress from the eclipse stage to the productively infected stage, the more likely that a viral strain will persist. Long-term treatment effectiveness of antiretroviral drugs is often hindered by the frequent emergence of drug resistant virus during therapy. We link drug resistance to both the rate of progression of the eclipse phase and the rate of viral production of the resistant strain, and explore how the resistant strain could evolve to maximize its within-host viral fitness. We obtained the optimal progression rate and the optimal viral production rate, which maximize the fitness of a drug resistant strain in the presence of drugs. We show that the window of opportunity for invasion of drug resistant strains is widened for a higher level of drug efficacy provided that the treatment is not potent enough to eradicate both the sensitive and resistant virus. PMID:17532343

  5. Entrapment of Viral Capsids in Nuclear PML Cages Is an Intrinsic Antiviral Host Defense against Varicella-Zoster Virus

    Science.gov (United States)

    Reichelt, Mike; Wang, Li; Sommer, Marvin; Perrino, John; Nour, Adel M.; Sen, Nandini; Baiker, Armin; Zerboni, Leigh; Arvin, Ann M.

    2011-01-01

    The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant

  6. Coxsackievirus B exits the host cell in shed microvesicles displaying autophagosomal markers.

    Directory of Open Access Journals (Sweden)

    Scott M Robinson

    2014-04-01

    Full Text Available Coxsackievirus B3 (CVB3, a member of the picornavirus family and enterovirus genus, causes viral myocarditis, aseptic meningitis, and pancreatitis in humans. We genetically engineered a unique molecular marker, "fluorescent timer" protein, within our infectious CVB3 clone and isolated a high-titer recombinant viral stock (Timer-CVB3 following transfection in HeLa cells. "Fluorescent timer" protein undergoes slow conversion of fluorescence from green to red over time, and Timer-CVB3 can be utilized to track virus infection and dissemination in real time. Upon infection with Timer-CVB3, HeLa cells, neural progenitor and stem cells (NPSCs, and C2C12 myoblast cells slowly changed fluorescence from green to red over 72 hours as determined by fluorescence microscopy or flow cytometric analysis. The conversion of "fluorescent timer" protein in HeLa cells infected with Timer-CVB3 could be interrupted by fixation, suggesting that the fluorophore was stabilized by formaldehyde cross-linking reactions. Induction of a type I interferon response or ribavirin treatment reduced the progression of cell-to-cell virus spread in HeLa cells or NPSCs infected with Timer-CVB3. Time lapse photography of partially differentiated NPSCs infected with Timer-CVB3 revealed substantial intracellular membrane remodeling and the assembly of discrete virus replication organelles which changed fluorescence color in an asynchronous fashion within the cell. "Fluorescent timer" protein colocalized closely with viral 3A protein within virus replication organelles. Intriguingly, infection of partially differentiated NPSCs or C2C12 myoblast cells induced the release of abundant extracellular microvesicles (EMVs containing matured "fluorescent timer" protein and infectious virus representing a novel route of virus dissemination. CVB3 virions were readily observed within purified EMVs by transmission electron microscopy, and infectious virus was identified within low-density isopycnic

  7. Coxsackievirus B exits the host cell in shed microvesicles displaying autophagosomal markers.

    Science.gov (United States)

    Robinson, Scott M; Tsueng, Ginger; Sin, Jon; Mangale, Vrushali; Rahawi, Shahad; McIntyre, Laura L; Williams, Wesley; Kha, Nelson; Cruz, Casey; Hancock, Bryan M; Nguyen, David P; Sayen, M Richard; Hilton, Brett J; Doran, Kelly S; Segall, Anca M; Wolkowicz, Roland; Cornell, Christopher T; Whitton, J Lindsay; Gottlieb, Roberta A; Feuer, Ralph

    2014-04-01

    Coxsackievirus B3 (CVB3), a member of the picornavirus family and enterovirus genus, causes viral myocarditis, aseptic meningitis, and pancreatitis in humans. We genetically engineered a unique molecular marker, "fluorescent timer" protein, within our infectious CVB3 clone and isolated a high-titer recombinant viral stock (Timer-CVB3) following transfection in HeLa cells. "Fluorescent timer" protein undergoes slow conversion of fluorescence from green to red over time, and Timer-CVB3 can be utilized to track virus infection and dissemination in real time. Upon infection with Timer-CVB3, HeLa cells, neural progenitor and stem cells (NPSCs), and C2C12 myoblast cells slowly changed fluorescence from green to red over 72 hours as determined by fluorescence microscopy or flow cytometric analysis. The conversion of "fluorescent timer" protein in HeLa cells infected with Timer-CVB3 could be interrupted by fixation, suggesting that the fluorophore was stabilized by formaldehyde cross-linking reactions. Induction of a type I interferon response or ribavirin treatment reduced the progression of cell-to-cell virus spread in HeLa cells or NPSCs infected with Timer-CVB3. Time lapse photography of partially differentiated NPSCs infected with Timer-CVB3 revealed substantial intracellular membrane remodeling and the assembly of discrete virus replication organelles which changed fluorescence color in an asynchronous fashion within the cell. "Fluorescent timer" protein colocalized closely with viral 3A protein within virus replication organelles. Intriguingly, infection of partially differentiated NPSCs or C2C12 myoblast cells induced the release of abundant extracellular microvesicles (EMVs) containing matured "fluorescent timer" protein and infectious virus representing a novel route of virus dissemination. CVB3 virions were readily observed within purified EMVs by transmission electron microscopy, and infectious virus was identified within low-density isopycnic iodixanol

  8. Recombination hotspots and host susceptibility modulate the adaptive value of recombination during maize streak virus evolution

    Directory of Open Access Journals (Sweden)

    Monjane Adérito L

    2011-12-01

    Full Text Available Abstract Background Maize streak virus -strain A (MSV-A; Genus Mastrevirus, Family Geminiviridae, the maize-adapted strain of MSV that causes maize streak disease throughout sub-Saharan Africa, probably arose between 100 and 200 years ago via homologous recombination between two MSV strains adapted to wild grasses. MSV recombination experiments and analyses of natural MSV recombination patterns have revealed that this recombination event entailed the exchange of the movement protein - coat protein gene cassette, bounded by the two genomic regions most prone to recombination in mastrevirus genomes; the first surrounding the virion-strand origin of replication, and the second around the interface between the coat protein gene and the short intergenic region. Therefore, aside from the likely adaptive advantages presented by a modular exchange of this cassette, these specific breakpoints may have been largely predetermined by the underlying mechanisms of mastrevirus recombination. To investigate this hypothesis, we constructed artificial, low-fitness, reciprocal chimaeric MSV genomes using alternating genomic segments from two MSV strains; a grass-adapted MSV-B, and a maize-adapted MSV-A. Between them, each pair of reciprocal chimaeric genomes represented all of the genetic material required to reconstruct - via recombination - the highly maize-adapted MSV-A genotype, MSV-MatA. We then co-infected a selection of differentially MSV-resistant maize genotypes with pairs of reciprocal chimaeras to determine the efficiency with which recombination would give rise to high-fitness progeny genomes resembling MSV-MatA. Results Recombinants resembling MSV-MatA invariably arose in all of our experiments. However, the accuracy and efficiency with which the MSV-MatA genotype was recovered across all replicates of each experiment depended on the MSV susceptibility of the maize genotypes used and the precise positions - in relation to known recombination hotspots

  9. EXTRACTIVE INDUSTRIES, THE STATE AND HOST COM ...

    African Journals Online (AJOL)

    PUBLICATIONS1

    tions between mining companies and host com- munities are adversarial. The book clearly poses that the Ministry of Lands, Forestry and. Mines (now Ministry of Lands and Natural. Resources) is responsible for implementing mining policy in Ghana and each of these three sectors is represented nationwide by commis-.

  10. Detecting Intermediary Hosts by TCP Latency Measurements

    Science.gov (United States)

    Singh, Gurvinder; Eian, Martin; Willassen, Svein Y.; Mjølsnes, Stig Fr.

    Use of intermediary hosts as stepping stones to conceal tracks is common in Internet misuse. It is therefore desirable to find a method to detect whether the originating party is using an intermediary host. Such a detection technique would allow the activation of a number of countermeasures that would neutralize the effects of misuse, and make it easier to trace a perpetrator. This work explores a new approach in determining if a host communicating via TCP is the data originator or if it is acting as a mere TCP proxy. The approach is based on measuring the inter packet arrival time at the receiving end of the connection only, and correlating the observed results with the network latency between the receiver and the proxy. The results presented here indicate that determining the use of a proxy host is possible, if the network latency between the originator and proxy is larger than the network latency between the proxy and the receiver. We show that this technique has potential to be used to detect connections were data is sent through a TCP proxy, such as remote login through TCP proxies, or rejecting spam sent through a bot network.

  11. Microbial manipulation of host sex determination

    NARCIS (Netherlands)

    Beukeboom, Leo W.

    A recent study in the lepidopteran Ostrinia scapulalis shows that endosymbionts can actively manipulate the sex determination mechanism of their host. Wolbachia bacteria alter the sex-specific splicing of the doublesex master switch gene. In ZZ males of this female heterogametic system, the female

  12. Host range evaluation and morphological characterization of ...

    African Journals Online (AJOL)

    USER

    2010-08-02

    Aug 2, 2010 ... pathogens” with high evolutionary potential (Sarris et al.,. 2008). Pathogenic and morphological variation of this oomycete appear to be correlated with host and environ- mental conditions (Lebeda and Widrlechner, 2003), and significant variation has been found at both the individual and population levels.

  13. Host selection by a kleptobiotic spider

    Science.gov (United States)

    Hénaut, Yann; Delme, Juliette; Legal, Luc; Williams, Trevor

    2005-02-01

    Why do kleptobiotic spiders of the genus Argyrodes seem to be associated with spiders of the genus Nephila worldwide? Observations following introduction of experimental insect prey of different sizes and weights on to host webs revealed that: (1) small prey are more effectively retained on the web of Nephila clavipes than on the web of another common host, Leucauge venusta. (2) N. clavipes did not consume small prey that accumulated on the web whereas larger, heavier prey were enveloped and stored. (3) We observed clear partitioning of prey items between N. clavipes and Argyrodes spp.; diet selection by Argyrodes did not overlap with that of N. clavipes but closely overlapped with that of L. venusta. (4) L. venusta responds very quickly to prey impact whereas N. clavipes is slower, offering a temporal window of opportunity for Argyrodes foraging. (5) The ability of L. venusta to detect and respond to small items also means that it acts aggressively to Argyrodes spp., whereas N. clavipes does not. Consequently, food-acquisition behaviours of Argyrodes were clearly less risky with N. clavipes compared with L. venusta. We conclude that when a kleptobiotic organism has a choice of various host species, it will opt for the least risky host that presents the highest rate of availability of food items. The fact that Nephila species present such characteristics explains the worldwide association with Argyrodes kleptobiotic spiders.

  14. The Swift GRB Host Galaxy Legacy Survey

    Science.gov (United States)

    Perley, Daniel A.

    I will describe the Swift Host Galaxy Legacy Survey (SHOALS), a comprehensive multiwavelengthprogram to characterize the demographics of the GRB host population and its redshift evolution from z=0 to z=7.Using unbiased selection criteria we have designated a subset of 119 Swift gamma-ray bursts which are now beingtargeted with intensive observational follow-up. Deep Spitzer imaging of every field has already been obtained andanalyzed, with major programs ongoing at Keck, GTC, Gemini, VLT, and Magellan to obtain complementaryoptical/NIR photometry and spectroscopy to enable full SED modeling and derivation of fundamental physicalparameters such as mass, extinction, and star-formation rate. Using these data I will present an unbiasedmeasurement of the GRB host-galaxy luminosity and mass distributions and their evolution with redshift, compareGRB hosts to other star-forming galaxy populations, and discuss implications for the nature of the GRB progenitor andthe ability of GRBs to serve as tools for measuring and studying cosmic star-formation in the distant universe.

  15. Host-pathogen interactions in typhoid fever

    NARCIS (Netherlands)

    de Jong, H.K.

    2015-01-01

    This thesis focuses on host-pathogen interactions in Salmonella Typhi and Burkholderia pseudomallei infections and explores the interplay between these bacteria and the innate immune system. Typhoid fever is one of the most common causes of bacterial infection in low-income countries. With adequate

  16. Host country language ability and expatriate adjustment

    DEFF Research Database (Denmark)

    Selmer, Jan; Lauring, Jakob

    2015-01-01

    countries, one with an easy, relatively simple language and the other with a difficult, highly complex language. Consistent with Goal-Setting Theory, results indicated a relative advantage of expatriates’ language ability in terms of their adjustment in the host country with the difficult language...

  17. EFFECT OF TEMPERATURE AND HOST GENOTYPE ON ...

    African Journals Online (AJOL)

    Disease development in plants involves various inter-related processes each of which may be. influenced by environmental factors as well as host and pathogen genotypes Temperature in the range of 20~25°C was reported to be optimum for urediniospore germination of groundnut rust. (Subrahmanyam and McDonald ...

  18. Systems analysis of host-parasite interactions.

    Science.gov (United States)

    Swann, Justine; Jamshidi, Neema; Lewis, Nathan E; Winzeler, Elizabeth A

    2015-01-01

    Parasitic diseases caused by protozoan pathogens lead to hundreds of thousands of deaths per year in addition to substantial suffering and socioeconomic decline for millions of people worldwide. The lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites necessitates that the research community take an active role in understanding host-parasite infection biology in order to develop improved therapeutics. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host-parasite interactions. Over the past decade, these technologies have led to the discovery of many important biological processes governing parasitic disease. The integration and interpretation of high-throughput -omic data will undoubtedly generate extraordinary insight into host-parasite interaction networks essential to navigate the intricacies of these complex systems. As systems analysis continues to build the foundation for our understanding of host-parasite biology, this will provide the framework necessary to drive drug discovery research forward and accelerate the development of new antiparasitic therapies. © 2015 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc.

  19. Five bid to host Middle East synchroton

    CERN Multimedia

    McCabe, H

    1999-01-01

    Germany is willing to donate a synchrotron to a research centre to be built somewhere in the Middle East. Bids to host the centre were submitted by Turkey, Cyprus, Iran, the Palestinian Authority and Egypt. Funding of at least 30 million US dollars still needs to be found (1 page).

  20. Host range of emerald ash borer

    Science.gov (United States)

    Robert A. Haack; Toby R. Petrice; Deborah L. Miller; Leah S. Bauer; Nathan M. Schiff

    2004-01-01

    The emerald ash borer (EAB), Agrilus planipennis Fairmaire, is native to China, Korea, Japan, Mongolia, Russia, and Taiwan (Haack et al. 2002). Established populations of EAB were first discovered in Michigan and Ontario in 2002. Smaller populations, which resulted from human assisted movement of infested host material, were found in Ohio, Maryland,...

  1. Host range evaluation and morphological characterization of ...

    African Journals Online (AJOL)

    A total of 29 isolates of Pseudoperonospora cubensis were collected from various cucurbit farms in West Malaysia. Sporangia of 13 isolates had the ability to germinate at 14°C and were used for host range (pathotype) study using leaf disc assay on a set of twelve cucurbit cultivars. Twelve different pathotypes of P. cubensis ...

  2. Studies of Reservoir Hosts for Marburg virus

    DEFF Research Database (Denmark)

    Swanepoel, Robert; Smit, Sheilagh B; Rollin, Pierre E

    2007-01-01

    To determine reservoir hosts for Marburg virus (MARV), we examined the fauna of a mine in northeastern Democratic Republic of the Congo. The mine was associated with a protracted outbreak of Marburg hemorrhagic fever during 1998-2000. We found MARV nucleic acid in 12 bats, comprising 3.0%-3.6% of 2...

  3. Host-pathogen interactions during apoptosis

    Indian Academy of Sciences (India)

    Unknown

    The adenovirus E3-14⋅7 K protein, expressed early in the life cycle of human adenoviruses to protect the virus from the antiviral response of host cells, inhibits cell death mediated by TNF-α and FasL receptors. Specific induction of apoptosis in immune cells is seen in HIV infections (Pantaleo and Fauci 1995). HIV kills ...

  4. SHORT COMMUNICATION: EVALUATION OF HOST-PATHOGEN ...

    African Journals Online (AJOL)

    SHORT COMMUNICATION: EVALUATION OF HOST-PATHOGEN INTERACTION OF MYCOVELLOSIELLA CAJAN WITH PIGEONPEA. ... produit dans les feuilles de pigeonpea susceptibles 16 à 18 jours après l'inoculation et dans les variétés résistantes, les conidiophores n'étaient pas observés même après 16 jours.

  5. Spectroscopic Analysis of Planetary Host Stars

    Science.gov (United States)

    Rittipruk, P.; Yushchenko, A.; Kang, Y. W.

    2014-08-01

    We observed the high resolution spectra of extra-solar planet host stars. The spectroscopic data of host stars were observed using the CHIRON echelle spectrometer and R-C Spectrograph for magnetic activity on the SMART-1.5 meter telescope at CTIO, Chile. The analysis of spectroscopic data was performed using URAN and SYNTHE programs. These spectra allow us to determine the effective temperatures, surface gravities, microturbulent velocities and, finally, the chemical composition of the hosts was obtained by spectrum synthesis. One of the targets, namely HD 47536, the host of two planets, appeared to be a halo star with overabundances of neutron capture elements. The effective temperature and the surface gravity of this star are 4400 K and log=1.5 respectively, the iron is underabundant by 0.6 dex. The heavy elements (up to thorium, Z=90) show the overabundances with respect to iron. The signs of accretion of interstellar gas are found in the atmosphere of this star.

  6. Gut microbiota, host gene expression, and aging.

    Science.gov (United States)

    Patrignani, Paola; Tacconelli, Stefania; Bruno, Annalisa

    2014-01-01

    Novel concepts of disease susceptibility and development suggest an important role of gastrointestinal microbiota and microbial pathogens. They can contribute to physiological systems and disease processes, even outside of the gastrointestinal tract. There is increasing evidence that genetics of the host influence and interact with gut microbiota. Moreover, aging-associated oxidative stress may cause morphologic alterations of bacterial cells, thus influencing the aggressive potential and virulence markers of an anaerobic bacterium and finally the type of interaction with the host. At the same time, microbiota may influence host gene expression and it is becoming apparent that it may occur through the regulation of microRNAs. They are short single-stranded noncoding RNAs that regulate posttranscriptional gene expression by affecting mRNA stability and/or translational repression of their target mRNAs. The introduction of -omics approaches (such as metagenomics, metaproteomics, and metatranscriptomics) in microbiota research will certainly advance our knowledge of this area. This will lead to greatly deepen our understanding of the molecular targets in the homeostatic interaction between the gut microbiota and the host and, thereby, promises to reveal new ways to treat diseases and maintain health.

  7. Influence of host profitability and microenvironmental conditions on parasite specialization on a main and an alternative hosts.

    Science.gov (United States)

    Lemoine, M; Doligez, B; Passerault, M; Richner, H

    2011-06-01

    Parasite success depends on both host profitability and the microenvironment provided by the host, which together define host-parasite compatibility and can differ between hosts. We experimentally disentangled the effects of host profitability and microenvironmental conditions provided by nest material on the reproduction of a nest-based ectoparasite when exploiting its main and an alternative avian host species. Parasite reproductive performance was similar on both hosts when breeding in nests of their own species, suggesting no difference in host-parasite compatibility between hosts. The apparent parasite specialization could therefore result from differences in host-parasite encounter processes. However, when hosts were successful, the main host produced more young in infested nests, whereas the alternative host produced less; furthermore, host reproductive performance was higher in nests of the main host species, suggesting that this nest material alleviates parasitism cost. Therefore, our results suggest different evolutionary responses to parasites of the main and alternative hosts, with either higher tolerance or higher resistance, modulated by nest material. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  8. Trophic relationships between the parasitic plant species Phelipanche ramosa (L. and different hosts depending on host phenological stage and host growth rate

    Directory of Open Access Journals (Sweden)

    Delphine Moreau

    2016-07-01

    Full Text Available Phelipanche ramosa (L. Pomel (branched broomrape is a holoparasitic plant that reproduces on crops and also on weeds, which contributes to increase the parasite seed bank in fields. This parasite extracts all its nutrients at the host's expense so that host-parasite trophic relationships are crucial to determine host and parasite growth. This study quantified the intensity with which P. ramosa draws assimilates from its host and analyzed whether it varied with host species, host phenological stage and host growth rate. A greenhouse experiment was conducted on three host species: the crop species Brassica napus (L. (oilseed rape and two weed species, Capsella bursa-pastoris (L. Medik. and Geranium dissectum (L.. Plants were grown with or without P. ramosa and under three light levels to modulate host growth rate. The proportion of host biomass loss due to parasitism by P. ramosa differed between host species (at host fructification, biomass loss ranged from 34% to 84%. Brassica napus and C. bursa-pastoris displayed a similar response to P. ramosa, probably because they belong to the same botanical family. The sensitivity to P. ramosa in each host species could be related to the precocity of P. ramosa development on them. Host compartments could be ranked as a function of their sensitivity to parasitism, with the reproductive compartment being the most severely affected, followed by stems and roots. The proportion of biomass allocated to leaves was not reduced by parasitism. The proportion of pathosystem biomass allocated to the parasite depended on host species. It generally increased with host stage progression but was constant across light induced-host growth rate, showing that P. ramosa adapts its growth to host biomass production. The rank order of host species in terms of sink strength differed from that in terms of host sensitivity. Finally, for B. napus, the biomass of individual parasite shoots decreased with increasing their number per

  9. Dietary Fiber Gap and Host Gut Microbiota.

    Science.gov (United States)

    Han, Meng; Wang, Congmin; Liu, Ping; Li, Defa; Li, Yuan; Ma, Xi

    2017-05-10

    Accumulating evidence is dramatically increasing the access to the facts that the gut microbiota plays a pivotal role in host metabolism and health, which revealed the possibility of a plethora of associations between gut bacteria and human diseases. Several functional roles are carried out by a major class of the host's diet, such as fiber. Fiber is the main source of microbiota-accessible carbohydrate in the diet of humans. In the modern diet, it is difficult to intake sufficient dietary fiber as recommended. The low-fiber diet in the modern life, known as fiber gap, can trigger a substantial depletion of the human gut microbiota diversity and beneficial metabolites. The short-chain fatty acids are regarded as one of the major microbial metabolites of dietary fibers, which can improve intestinal mucosal immunity, as well as to be a source of energy for the liver. Thus, the loss of microbiota diversity has a potential negative function to various aspects of host health. Actually, the real "fiber gap" for ideal health and maintaining microbial diversity might be even more serious than currently appreciated. Herein, we briefly discuss the interactions between gut microbiota and the host diet, focusing specifically on the low-fiber diet. Gut bacteria in the context of the development of host low-fiber diets, which may lead to health and disorders, particularly include metabolic syndrome and obesity-related disease, IBD liver, disease, and colorectal cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Citrus tristeza virus-host interactions

    Directory of Open Access Journals (Sweden)

    William O. Dawson

    2013-05-01

    Full Text Available Citrus tristeza virus (CTV is a phloem-limited virus whose natural host range is restricted to citrus and related species. Although the virus has killed millions of trees, almost destroying whole industries, and continually limits production in many citrus growing areas, most isolates are mild or symptomless in most of their host range. There is little understanding of how the virus causes severe disease in some citrus and none in others. Movement and distribution of CTV differs considerably from that of well-studied viruses of herbaceous plants where movement occurs largely through adjacent cells. In contrast, CTV systemically infects plants mainly by long-distance movement with only limited cell-to-cell movement. The virus is transported through sieve elements and occasionally enters an adjacent companion or phloem parenchyma cell where virus replication occurs. In some plants this is followed by cell-to-cell movement into only a small cluster of adjacent cells, while in others there is no cell-to-cell movement. Different proportions of cells adjacent to sieve elements become infected in different plant species. This appears to be related to how well viral gene products interact with specific hosts. CTV has three genes that are not necessary for infection of most of its hosts, but are needed in different combinations for infection of certain citrus species. These genes apparently were acquired by the virus to extend its host range. Some specific viral gene products have been implicated in symptom induction. Remarkably, the deletion of these genes from the virus genome can induce large increases in stem pitting symptoms. The p23 gene, which is a suppressor of RNA silencing and a regulator of viral RNA synthesis, has been shown to be the cause of seedling yellows symptoms in sour orange. Most isolates of CTV in nature are populations of different strains of CTV. The next frontier of CTV biology is the understanding how the virus variants in

  11. Star Formation Quenching in Quasar Host Galaxies

    Directory of Open Access Journals (Sweden)

    Stefano Carniani

    2017-10-01

    Full Text Available Galaxy evolution is likely to be shaped by negative feedback from active galactic nuclei (AGN. In the whole range of redshifts and luminosities studied so far, galaxies hosting an AGN frequently show fast and extended outflows consisting in both ionized and molecular gas. Such outflows could potentially quench the start formation within the host galaxy, but a clear evidence of negative feedback in action is still missing. Hereby I will analyse integral-field spectroscopic data for six quasars at z ~ 2.4 obtained with SINFONI in the H- and K-band. All the quasars show [Oiii]λ5007 line detection of fast, extended outflows. Also, the high signal-to-noise SINFONI observations allow the identification of faint narrow Hα emission (FWHM < 500 km/s, which is spatially extended and associated with star formation in the host galaxy. On paper fast outflows are spatially anti-correlated with star-formation powered emission, i.e., star formation is suppressed in the area affected by the outflow. Nonetheless as narrow, spatially-extended Hα emission, indicating star formation rates of at least 50–100 M⊙ yr−1, has been detected, either AGN feedback is not affecting the whole host galaxy, or star formation is completely quenched only by several feedback episodes. On the other hand, a positive feedback scenario, supported by narrow emission in Hα extending along the edges of the outflow cone, suggests that galaxy-wide outflows could also have a twofold role in the evolution of the host galaxy. Finally, I will present CO(3-2 ALMA data for three out of the six QSOs observed with SINFONI. Flux maps obtained for the CO(3-2 transition suggest that molecular gas within the host galaxy is swept away by fast winds. A negative-feedback scenario is supported by the inferred molecular gas mass in all three objects, which is significantly below what observed in non-active main-sequence galaxies at high-z.

  12. Divergence in olfactory host plant preference in D. mojavensis in response to cactus host use.

    Science.gov (United States)

    Date, Priya; Dweck, Hany K M; Stensmyr, Marcus C; Shann, Jodi; Hansson, Bill S; Rollmann, Stephanie M

    2013-01-01

    Divergence in host adaptive traits has been well studied from an ecological and evolutionary perspective, but identification of the proximate mechanisms underlying such divergence is less well understood. Behavioral preferences for host plants are often mediated by olfaction and shifts in preference may be accompanied by changes in the olfactory system. In this study, we examine the evolution of host plant preferences in cactophilic Drosophila mojavensis that feeds and breeds on different cacti throughout its range. We show divergence in electrophysiological responses and olfactory behavior among populations with host plant shifts. Specifically, significant divergence was observed in the Mojave Desert population that specializes on barrel cactus. Differences were observed in electrophysiological responses of the olfactory organs and in behavioral responses to barrel cactus volatiles. Together our results suggest that the peripheral nervous system has changed in response to different ecological environments and that these changes likely contribute to divergence among D. mojavensis populations.

  13. Divergence in olfactory host plant preference in D. mojavensis in response to cactus host use.

    Directory of Open Access Journals (Sweden)

    Priya Date

    Full Text Available Divergence in host adaptive traits has been well studied from an ecological and evolutionary perspective, but identification of the proximate mechanisms underlying such divergence is less well understood. Behavioral preferences for host plants are often mediated by olfaction and shifts in preference may be accompanied by changes in the olfactory system. In this study, we examine the evolution of host plant preferences in cactophilic Drosophila mojavensis that feeds and breeds on different cacti throughout its range. We show divergence in electrophysiological responses and olfactory behavior among populations with host plant shifts. Specifically, significant divergence was observed in the Mojave Desert population that specializes on barrel cactus. Differences were observed in electrophysiological responses of the olfactory organs and in behavioral responses to barrel cactus volatiles. Together our results suggest that the peripheral nervous system has changed in response to different ecological environments and that these changes likely contribute to divergence among D. mojavensis populations.

  14. Host density increases parasite recruitment but decreases host risk in a snail-trematode system

    Science.gov (United States)

    Buck, Julia C; Hechinger, R.F.; Wood, A.C.; Stewart, T.E.; Kuris, A.M.; Lafferty, Kevin D.

    2017-01-01

    Most species aggregate in local patches. High host density in patches increases contact rate between hosts and parasites, increasing parasite transmission success. At the same time, for environmentally-transmitted parasites, high host density can decrease infection risk to individual hosts, because infective stages are divided among all hosts in a patch, leading to safety in numbers. We tested these predictions using the California horn snail, Cerithideopsis californica (=Cerithidea californica), which is the first intermediate host for at least 19 digenean trematode species in California estuaries. Snails become infected by ingesting trematode eggs or through penetration by free-swimming miracidia that hatch from trematode eggs deposited with final-host (bird or mammal) feces. This complex life cycle decouples infective-stage production from transmission, raising the possibility of an inverse relationship between host density and infection risk. In a field survey, higher snail density was associated with increased trematode (infected snail) density, but decreased trematode prevalence, consistent with either safety in numbers, parasitic castration, or both. To determine the extent to which safety in numbers drove the negative snail density-trematode prevalence association, we manipulated uninfected snail density in 83 cages at eight sites within Carpinteria Salt Marsh (CA, USA). At each site, we quantified snail density and used data on final-host (bird and raccoon) distributions to control for between-site variation in infective-stage supply. After three months, overall trematode infections per cage increased with snail-biomass density. For egg-transmitted trematodes, per-snail infection risk decreased with snail-biomass density in the cage and surrounding area, whereas per-snail infection risk did not decrease for miracidium-transmitted trematodes. Furthermore, both trematode recruitment and infection risk increased with infective-stage input, but this was

  15. Host density increases parasite recruitment but decreases host risk in a snail-trematode system.

    Science.gov (United States)

    Buck, J C; Hechinger, R F; Wood, A C; Stewart, T E; Kuris, A M; Lafferty, K D

    2017-08-01

    Most species aggregate in local patches. High host density in patches increases contact rate between hosts and parasites, increasing parasite transmission success. At the same time, for environmentally transmitted parasites, high host density can decrease infection risk to individual hosts, because infective stages are divided among all hosts in a patch, leading to safety in numbers. We tested these predictions using the California horn snail, Cerithideopsis californica (=Cerithidea californica), which is the first intermediate host for at least 19 digenean trematode species in California estuaries. Snails become infected by ingesting trematode eggs or through penetration by free-swimming miracidia that hatch from trematode eggs deposited with final-host (bird or mammal) feces. This complex life cycle decouples infective-stage production from transmission, raising the possibility of an inverse relationship between host density and infection risk at local scales. In a field survey, higher snail density was associated with increased trematode (infected snail) density, but decreased trematode prevalence, consistent with either safety in numbers, parasitic castration, or both. To determine the extent to which safety in numbers drove the negative snail-density-trematode-prevalence association, we manipulated uninfected snail density in 83 cages at eight sites within Carpinteria Salt Marsh (California, USA). At each site, we quantified snail density and used data on final-host (bird and raccoon) distributions to control for between-site variation in infective-stage supply. After three months, overall trematode infections per cage increased with snail biomass density. For egg-transmitted trematodes, per-snail infection risk decreased with snail biomass density in the cage and surrounding area, whereas per-snail infection risk did not decrease for miracidium-transmitted trematodes. Furthermore, both trematode recruitment and infection risk increased with infective

  16. Host Specificity in the Parasitic Plant Cytinus hypocistis

    Directory of Open Access Journals (Sweden)

    C. J. Thorogood

    2007-01-01

    Full Text Available Host specificity in the parasitic plant Cytinus hypocistis was quantified at four sites in the Algarve region of Portugal from 2002 to 2007. The parasite was found to be locally host specific, and only two hosts were consistently infected: Halimium halimifolium and Cistus monspeliensis. C. hypocistis did not infect hosts in proportion to their abundance; at three sites, 100% of parasites occurred on H. halimifolium which represented just 42.4%, 3% and 19.7% of potential hosts available, respectively. At the remaining site, where H. halimifolium was absent, 100% of parasites occurred on C. monspeliensis which represented 81.1% of potential hosts available. Other species of potential host were consistently uninfected irrespective of their abundance. Ecological niche divergence of host plants H. halimifolium and C. monspeliensis may isolate host-specific races of C. hypocistis, thereby potentially driving allopatric divergence in this parasitic plant.

  17. Parasites of cephalopods in the northern Tyrrhenian Sea (western Mediterranean: new host records and host specificity

    Directory of Open Access Journals (Sweden)

    C. Gestal

    1999-03-01

    Full Text Available This paper examines the species composition of the parasite fauna and the values of infection for seven species of cephalopods in the Mediterranean at the Tyrrhenian Sea (West coast of Italy. Results suggest the important role of cephalopods as intermediate hosts in the life cycle of anisakine nematodes and pennellid copepods. The low host specificity (i. e., eurixenous condition of metazoan parasites in cephalopods worldwide is also reinforced.

  18. Infection dynamics at within-host and between-host scales

    OpenAIRE

    Severins, M.

    2012-01-01

    Developing and predicting the effect of control measures on the infection dynamics in parasite-host systems with many feedback loops between the different infection processes poses a challenge. Part of this challenge comes from the large heterogeneity often observed in these systems. The goal of this PhD thesis is to increase our understanding of these complex within and between-host infection dynamics through the creation of mathematical and computational models that are able to capture the ...

  19. Average Spectral Properties of Type Ia Supernova Host Galaxies

    Science.gov (United States)

    Uddin, Syed A.; Mould, Jeremy; Wang, Lifan

    2017-12-01

    We construct the average spectra of host galaxies of slower, faster, bluer, and redder Type Ia supernovae (SNe Ia) from the SDSS-II supernova survey. The average spectrum of slower declining (broader light curve width or higher stretch) SN Ia hosts shows stronger emission lines compared to the average spectrum of faster declining (narrower light curve width or lower stretch) SN Ia hosts. Using pPXF, we find that hosts of slower declining SNe Ia have metallicities that are, on average, 0.24 dex lower than average metallicities of faster declining SN Ia hosts. Similarly, redder SN Ia hosts have slightly higher metallicities than bluer SN Ia hosts. Lick index analysis of metallic lines and Balmer lines shows that faster declining SN Ia hosts have relatively higher metal content and have relatively older stellar populations compared with slower declining SN Ia hosts. We calculate average {{{H}}}α star formation rate (SFR), stellar mass, and the specific SFR (sSFR) of host galaxies in these subgroups of SNe Ia. We find that slower declining SN Ia hosts have significantly higher (> 5σ ) sSFR than faster declining SN Ia hosts. A Kolmogorov-Smirnov test shows that these two types of hosts originate from different parent distributions. Our results, when compared with the models of Childress et al., indicate that slower declining SNe Ia, being hosted in actively star-forming galaxies, are young (prompt) SNe Ia, originating from similar progenitor age groups.

  20. The herpes simplex virus UL20 protein functions in glycoprotein K (gK intracellular transport and virus-induced cell fusion are independent of UL20 functions in cytoplasmic virion envelopment

    Directory of Open Access Journals (Sweden)

    Kousoulas Konstantin G

    2007-11-01

    Full Text Available Abstract The HSV-1 UL20 protein (UL20p and glycoprotein K (gK are both important determinants of cytoplasmic virion morphogenesis and virus-induced cell fusion. In this manuscript, we examined the effect of UL20 mutations on the coordinate transport and Trans Golgi Network (TGN localization of UL20p and gK, virus-induced cell fusion and infectious virus production. Deletion of 18 amino acids from the UL20p carboxyl terminus (UL20 mutant 204t inhibited intracellular transport and cell-surface expression of both gK and UL20, resulting in accumulation of UL20p and gK in the endoplasmic reticulum (ER in agreement with the inability of 204t to complement UL20-null virus replication and virus-induced cell fusion. In contrast, less severe carboxyl terminal deletions of either 11 or six amino acids (UL20 mutants 211t and 216t, respectively allowed efficient UL20p and gK intracellular transport, cell-surface expression and TGN colocalization. However, while both 211t and 216t failed to complement for infectious virus production, 216t complemented for virus-induced cell fusion, but 211t did not. These results indicated that the carboxyl terminal six amino acids of UL20p were crucial for infectious virus production, but not involved in intracellular localization of UL20p/gK and concomitant virus-induced cell fusion. In the amino terminus of UL20, UL20p mutants were produced changing one or both of the Y38 and Y49 residues found within putative phosphorylation sites. UL20p tyrosine-modified mutants with both tyrosine residues changed enabled efficient intracellular transport and TGN localization of UL20p and gK, but failed to complement for either infectious virus production, or virus-induced cell fusion. These results show that UL20p functions in cytoplasmic envelopment are separable from UL20 functions in UL20p intracellular transport, cell surface expression and virus-induced cell fusion.

  1. Rapid evolution of virulence leading to host extinction under host-parasite coevolution.

    Science.gov (United States)

    Rafaluk, Charlotte; Gildenhard, Markus; Mitschke, Andreas; Telschow, Arndt; Schulenburg, Hinrich; Joop, Gerrit

    2015-06-13

    Host-parasite coevolution is predicted to result in changes in the virulence of the parasite in order to maximise its reproductive success and transmission potential, either via direct host-to-host transfer or through the environment. The majority of coevolution experiments, however, do not allow for environmental transmission or persistence of long lived parasite stages, in spite of the fact that these may be critical for the evolutionary success of spore forming parasites under natural conditions. We carried out a coevolution experiment using the red flour beetle, Tribolium castaneum, and its natural microsporidian parasite, Paranosema whitei. Beetles and their environment, inclusive of spores released into it, were transferred from generation to generation. We additionally took a modelling approach to further assess the importance of transmissive parasite stages on virulence evolution. In all parasite treatments of the experiment, coevolution resulted in extinction of the host population, with a pronounced increase in virulence being seen. Our modelling approach highlighted the presence of environmental transmissive parasite stages as being critical to the trajectory of virulence evolution in this system. The extinction of host populations was unexpected, particularly as parasite virulence is often seen to decrease in host-parasite coevolution. This, in combination with the increase in virulence and results obtained from the model, suggest that the inclusion of transmissive parasite stages is important to improving our understanding of virulence evolution.

  2. Host preference of the crapemyrtle aphid (Hemiptera: Aphididae) and host suitability of crapemyrtle cultivars.

    Science.gov (United States)

    Herbert, John J; Mizell, R F; McAuslane, H J

    2009-08-01

    Crapemyrtle aphids, Sarucallis kahawaluokalani (Kirkaldy), are a common pest of crapemyrtle (Lagerstroemia spp.) throughout the southeastern United States. Breeding programs have produced >100 crapemyrtle cultivars that vary in floral color, plant height, and disease resistance, but these programs did not evaluate insect resistance as part of the selection process. In this study, the host suitability of crapemyrtle cultivars and host preference of the crapemyrtle aphid were tested using the following seven crapemyrtle cultivars: 'Carolina Beauty', 'Byers Wonderful White', 'Apalachee', 'Lipan', 'Tuscarora', 'Sioux', and 'Natchez'. Host suitability or aphid preference may be affected by cultivar attributes of plant parentage, source of Lagerstroemia fauriei Koehne germplasm, and mature plant height. Host suitability was evaluated by measuring daily and total fecundity under no-choice conditions. Host preference of the crapemyrtle aphid was tested in a choice experiment that used eight crapemyrtle cultivars; the seven used in the no-choice experiment plus Lagerstroemia speciosa L. In the no-choice experiment, aphid daily fecundity was not different among the crapemyrtle cultivars, but aphid total fecundity was different for the factors cultivar, plant parentage, source of germplasm, and mature plant height. Crapemyrtle aphid host preference in the choice experiment indicated that there were differences among cultivar, parentage, source of germplasm, and mature plant height. Results from this study are useful for plant breeding programs that have the objective of producing aphid resistant cultivars.

  3. Lytic myophage Abp53 encodes several proteins similar to those encoded by host Acinetobacter baumannii and phage phiKO2.

    Science.gov (United States)

    Lee, Chia-Ni; Tseng, Tsai-Tien; Lin, Juey-Wen; Fu, Yung-Chieh; Weng, Shu-Fen; Tseng, Yi-Hsiung

    2011-10-01

    Acinetobacter baumannii is an important Gram-negative opportunistic pathogen causing nosocomial infections. The emergence of multiple-drug-resistant A. baumannii isolates has increased in recent years. Directed toward phage therapy, a lytic phage of A. baumannii, designated Abp53, was isolated from a sputum sample in this study. Abp53 has an isometric head and a contractile tail with tail fibers (belonging to Myoviridae), a latent period of about 10 min, and a burst size of approximately 150 PFU per infected cell. Abp53 could completely lyse 27% of the A. baumannii isolates tested, which were all multiple drug resistant, but not other bacteria. Mg(2+) enhanced the adsorption and productivity of, and host lysis by, Abp53. Twenty Abp53 virion proteins were visualized in SDS-polyacrylamide gel electrophoresis, with a 47-kDa protein being the predicted major capsid protein. Abp53 has a double-stranded DNA genome of 95 kb. Sequence analyses of a 10-kb region revealed 8 open reading frames. Five of the encoded proteins, including 3 tail components and 2 hypothetical proteins, were similar to proteins encoded by A. baumannii strain ACICU. ORF1176 (one of the tail components, 1,176 amino acids [aa]), which is also similar to tail protein gp21 of Klebsiella phage phiKO2, contained repeated domains similar to those within the ACICU_02717 protein of A. baumannii ACICU and gp21. These findings suggest a common ancestry and horizontal gene transfer during evolution. As phages can expand the host range by domain duplication in tail fiber proteins, repeated domains in ORF1176 might have a similar significance in Abp53.

  4. Lytic Myophage Abp53 Encodes Several Proteins Similar to Those Encoded by Host Acinetobacter baumannii and Phage phiKO2 ▿ †

    Science.gov (United States)

    Lee, Chia-Ni; Tseng, Tsai-Tien; Lin, Juey-Wen; Fu, Yung-Chieh; Weng, Shu-Fen; Tseng, Yi-Hsiung

    2011-01-01

    Acinetobacter baumannii is an important Gram-negative opportunistic pathogen causing nosocomial infections. The emergence of multiple-drug-resistant A. baumannii isolates has increased in recent years. Directed toward phage therapy, a lytic phage of A. baumannii, designated Abp53, was isolated from a sputum sample in this study. Abp53 has an isometric head and a contractile tail with tail fibers (belonging to Myoviridae), a latent period of about 10 min, and a burst size of approximately 150 PFU per infected cell. Abp53 could completely lyse 27% of the A. baumannii isolates tested, which were all multiple drug resistant, but not other bacteria. Mg2+ enhanced the adsorption and productivity of, and host lysis by, Abp53. Twenty Abp53 virion proteins were visualized in SDS-polyacrylamide gel electrophoresis, with a 47-kDa protein being the predicted major capsid protein. Abp53 has a double-stranded DNA genome of 95 kb. Sequence analyses of a 10-kb region revealed 8 open reading frames. Five of the encoded proteins, including 3 tail components and 2 hypothetical proteins, were similar to proteins encoded by A. baumannii strain ACICU. ORF1176 (one of the tail components, 1,176 amino acids [aa]), which is also similar to tail protein gp21 of Klebsiella phage phiKO2, contained repeated domains similar to those within the ACICU_02717 protein of A. baumannii ACICU and gp21. These findings suggest a common ancestry and horizontal gene transfer during evolution. As phages can expand the host range by domain duplication in tail fiber proteins, repeated domains in ORF1176 might have a similar significance in Abp53. PMID:21821767

  5. CERN hosts Physics and Society Forum

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    On 28-29 March, CERN hosted the fifth edition of the European Physical Society's “Physics and Society” forum. The forum addresses the role of physicists in general society – be they in education, politics, industry or communication. This year, attendees looked at how physicists have adapted - and can continue to adapt - to work in the economic marketplace.   “The forums began back in 2006, as a special closing event for the 2005 World Year of Physics,” explains Martial Ducloy, former President of the French Physical Society and Chair of the EPS Forum Physics and Society. “We decided to keep the sessions going, as they gave physicists a venue to discuss the non-scientific issues that influence their daily work. As the world's largest international physics laboratory – and the venue for this year's EPS Council – CERN seemed the ideal place to host this year's forum.” The forum ...

  6. Exploiting host immunity: the Salmonella paradigm

    Science.gov (United States)

    Behnsen, Judith; Perez-Lopez, Araceli; Nuccio, Sean-Paul; Raffatellu, Manuela

    2014-01-01

    Pathogens have evolved clever strategies to evade and in some cases exploit the attacks of an activated immune system. Salmonella enterica is one such pathogen, exploiting multiple aspects of host defense to promote its replication in the host. Here we review recent findings on the mechanisms by which Salmonella establishes systemic and chronic infection, including strategies involving manipulation of innate immune signaling and inflammatory forms of cell death, as well as immune evasion by establishing residency in M2 macrophages. We also examine recent evidence showing that the oxidative environment and the high levels of antimicrobial proteins produced in response to localized Salmonella gastrointestinal infection enable the pathogen to successfully outcompete the resident gut microbiota. PMID:25582038

  7. Host proteome research in HIV infection.

    Science.gov (United States)

    Zhang, Lijun; Zhang, Xiaojun; Ma, Qing; Zhou, Honghao

    2010-03-01

    Proteomics has been widely used in the last few years to look for new biomarkers and decipher the mechanism of HIV-host interaction. Herein, we review the recent developments of HIV/AIDS proteomic research, including the samples used in HIV/AIDS related research, the technologies used for proteomic study, the diagnosis biomarkers of HIV-associated disease especially HIV-associated neurocognitive impairment, the mechanisms of HIV-host interaction, HIV-associated dementia, substance abuse, and so on. In the end of this review, we also give some prospects about the limitation and future improvement of HIV/AIDS proteomic research. 2010 Beijing Genomics Institute. Published by Elsevier Ltd. All rights reserved.

  8. Trichinella inflammatory myopathy: host or parasite strategy?

    Science.gov (United States)

    2011-01-01

    The parasitic nematode Trichinella has a special relation with muscle, because of its unique intracellular localization in the skeletal muscle cell, completely devoted in morphology and biochemistry to become the parasite protective niche, otherwise called the nurse cell. The long-lasting muscle infection of Trichinella exhibits a strong interplay with the host immune response, mainly characterized by a Th2 phenotype. The aim of this review is to illustrate the role of the Th2 host immune response at the muscle level during trichinellosis in different experimental models, such as knock-out or immuno-modulated mice. In particular, in knock-out mice a crucial role of IL-10 is evident for the regulation of inflammation intensity. The muscular host immune response to Trichinella is partially regulated by the intestinal phase of the parasite which emphasizes the intensity of the following muscle inflammation compared with animals infected by synchronized injections of newborn larvae. In eosinophil-ablated mice such as PHIL and GATA-- animals it was observed that there was an increased NOS2 expression in macrophages, driven by higher IFN-γ release, thus responsible for muscle larva damage. Besides modulation of the intestinal stage of the infection, using recombinant IL-12, increases the muscular parasite burden delaying adult worm expulsion from the intestine. Furthermore, a Th1 adjuvant of bacterial origin called Helicobacter pylori neutrophil activating protein (HP-NAP), administered during the intestinal phase of trichinellosis, alters the Th2 dependent response at muscle level. All these data from the literature delineate then a mutual adaptation between parasite and host immune response in order to achieve a strategic compromise between two evolutionary forces pointed towards the survival of both species. PMID:21429196

  9. Identification of host response signatures of infection.

    Energy Technology Data Exchange (ETDEWEB)

    Branda, Steven S.; Sinha, Anupama; Bent, Zachary

    2013-02-01

    Biological weapons of mass destruction and emerging infectious diseases represent a serious and growing threat to our national security. Effective response to a bioattack or disease outbreak critically depends upon efficient and reliable distinguishing between infected vs healthy individuals, to enable rational use of scarce, invasive, and/or costly countermeasures (diagnostics, therapies, quarantine). Screening based on direct detection of the causative pathogen can be problematic, because culture- and probe-based assays are confounded by unanticipated pathogens (e.g., deeply diverged, engineered), and readily-accessible specimens (e.g., blood) often contain little or no pathogen, particularly at pre-symptomatic stages of disease. Thus, in addition to the pathogen itself, one would like to detect infection-specific host response signatures in the specimen, preferably ones comprised of nucleic acids (NA), which can be recovered and amplified from tiny specimens (e.g., fingerstick draws). Proof-of-concept studies have not been definitive, however, largely due to use of sub-optimal sample preparation and detection technologies. For purposes of pathogen detection, Sandia has developed novel molecular biology methods that enable selective isolation of NA unique to, or shared between, complex samples, followed by identification and quantitation via Second Generation Sequencing (SGS). The central hypothesis of the current study is that variations on this approach will support efficient identification and verification of NA-based host response signatures of infectious disease. To test this hypothesis, we re-engineered Sandia's sophisticated sample preparation pipelines, and developed new SGS data analysis tools and strategies, in order to pioneer use of SGS for identification of host NA correlating with infection. Proof-of-concept studies were carried out using specimens drawn from pathogen-infected non-human primates (NHP). This work provides a strong foundation for

  10. Modern condition and prospective host microecology investigations

    OpenAIRE

    Boris A. Shenderov

    2011-01-01

    This review considers data regarding fundamental and applied investigations in human microbial ecology received over the last 15 years. Analysis of these data enabled the author to come to the conclusion that in natural habitats there are practically no metabolic processes or physiological functions of a living being that would not need a direct or indirect participation of symbiotic microbiota. The condition of the host microbial ecology should be considered one of the main biogenic factors ...

  11. Symbiont-mediated functions in insect hosts

    OpenAIRE

    Su, Qi; Zhou, Xiaomao; Zhang, Youjun

    2013-01-01

    The bacterial endosymbionts occur in a diverse array of insect species and are usually rely within the vertical transmission from mothers to offspring. In addition to primary symbionts, plant sap-sucking insects may also harbor several diverse secondary symbionts. Bacterial symbionts play a prominent role in insect nutritional ecology by aiding in digestion of food or supplementing nutrients that insect hosts can?t obtain sufficient amounts from a restricted diet of plant phloem. Currently, s...

  12. Virus de inmunodeficiencia de simios: estudio de la participación del dominio citoplasmático de la glicoproteína viral de envoltura (Env) en la infectividad viral y en la incorporación de Env a viriones

    OpenAIRE

    Celma, Cristina Cecilia del Pilar

    2003-01-01

    En las últimas etapas del ciclo de replicación de los virus de immunodeficiencia de simios (SIV), ocurre el ensamblado de las partículas virales en la membrana plasmática de las células infectadas. Durante la morfogénesis de los viriones se produce la incorporación de la glicoproteína viral de envoltura (Env), proceso que es esencial para la infectividad viral. La glicoproteína Env se sintetiza como un precursor proteico, el cual es clivado en las subunidades de superficie y transmembrana por...

  13. The Toxoplasma Parasitophorous Vacuole: An Evolving Host-Parasite Frontier.

    Science.gov (United States)

    Clough, Barbara; Frickel, Eva-Maria

    2017-06-01

    The parasitophorous vacuole is a unique replicative niche for apicomplexan parasites, including Toxoplasma gondii. Derived from host plasma membrane, the vacuole is rendered nonfusogenic with the host endolysosomal system. Toxoplasma secretes numerous proteins to modify the forming vacuole, enable nutrient uptake, and set up mechanisms of host subversion. Here we describe the pathways of host-parasite interaction at the parasitophorous vacuole employed by Toxoplasma and host, leading to the intricate balance of host defence versus parasite survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Measles Virus Host Invasion and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Brigitta M. Laksono

    2016-07-01

    Full Text Available Measles virus is a highly contagious negative strand RNA virus that is transmitted via the respiratory route and causes systemic disease in previously unexposed humans and non-human primates. Measles is characterised by fever and skin rash and usually associated with cough, coryza and conjunctivitis. A hallmark of measles is the transient immune suppression, leading to increased susceptibility to opportunistic infections. At the same time, the disease is paradoxically associated with induction of a robust virus-specific immune response, resulting in lifelong immunity to measles. Identification of CD150 and nectin-4 as cellular receptors for measles virus has led to new perspectives on tropism and pathogenesis. In vivo studies in non-human primates have shown that the virus initially infects CD150+ lymphocytes and dendritic cells, both in circulation and in lymphoid tissues, followed by virus transmission to nectin-4 expressing epithelial cells. The abilities of the virus to cause systemic infection, to transmit to numerous new hosts via droplets or aerosols and to suppress the host immune response for several months or even years after infection make measles a remarkable disease. This review briefly highlights current topics in studies of measles virus host invasion and pathogenesis.

  15. Host specialist clownfishes are environmental niche generalists

    Science.gov (United States)

    Litsios, Glenn; Kostikova, Anna; Salamin, Nicolas

    2014-01-01

    Why generalist and specialist species coexist in nature is a question that has interested evolutionary biologists for a long time. While the coexistence of specialists and generalists exploiting resources on a single ecological dimension has been theoretically and empirically explored, biological systems with multiple resource dimensions (e.g. trophic, ecological) are less well understood. Yet, such systems may provide an alternative to the classical theory of stable evolutionary coexistence of generalist and specialist species on a single resource dimension. We explore such systems and the potential trade-offs between different resource dimensions in clownfishes. All species of this iconic clade are obligate mutualists with sea anemones yet show interspecific variation in anemone host specificity. Moreover, clownfishes developed variable environmental specialization across their distribution. In this study, we test for the existence of a relationship between host-specificity (number of anemones associated with a clownfish species) and environmental-specificity (expressed as the size of the ecological niche breadth across climatic gradients). We find a negative correlation between host range and environmental specificities in temperature, salinity and pH, probably indicating a trade-off between both types of specialization forcing species to specialize only in a single direction. Trade-offs in a multi-dimensional resource space could be a novel way of explaining the coexistence of generalist and specialists. PMID:25274370

  16. Deforestation homogenizes tropical parasitoid-host networks.

    Science.gov (United States)

    Laliberté, Etienne; Tylianakis, Jason M

    2010-06-01

    Human activities drive biotic homogenization (loss of regional diversity) of many taxa. However, whether species interaction networks (e.g., food webs) can also become homogenized remains largely unexplored. Using 48 quantitative parasitoid-host networks replicated through space and time across five tropical habitats, we show that deforestation greatly homogenized network structure at a regional level, such that interaction composition became more similar across rice and pasture sites compared with forested habitats. This was not simply caused by altered consumer and resource community composition, but was associated with altered consumer foraging success, such that parasitoids were more likely to locate their hosts in deforested habitats. Furthermore, deforestation indirectly homogenized networks in time through altered mean consumer and prey body size, which decreased in deforested habitats. Similar patterns were obtained with binary networks, suggesting that interaction (link) presence-absence data may be sufficient to detect network homogenization effects. Our results show that tropical agroforestry systems can support regionally diverse parasitoid-host networks, but that removal of canopy cover greatly homogenizes the structure of these networks in space, and to a lesser degree in time. Spatiotemporal homogenization of interaction networks may alter coevolutionary outcomes and reduce ecological resilience at regional scales, but may not necessarily be predictable from community changes observed within individual trophic levels.

  17. Citrus tristeza virus-host interactions

    Science.gov (United States)

    Dawson, W. O.; Garnsey, S. M.; Tatineni, S.; Folimonova, S. Y.; Harper, S. J.; Gowda, S.

    2013-01-01

    Citrus tristeza virus (CTV) is a phloem-limited virus whose natural host range is restricted to citrus and related species. Although the virus has killed millions of trees, almost destroying whole industries, and continually limits production in many citrus growing areas, most isolates are mild or symptomless in most of their host range. There is little understanding of how the virus causes severe disease in some citrus and none in others. Movement and distribution of CTV differs considerably from that of well-studied viruses of herbaceous plants where movement occurs largely through adjacent cells. In contrast, CTV systemically infects plants mainly by long-distance movement with only limited cell-to-cell movement. The virus is transported through sieve elements and occasionally enters an adjacent companion or phloem parenchyma cell where virus replication occurs. In some plants this is followed by cell-to-cell movement into only a small cluster of adjacent cells, while in others there is no cell-to-cell movement. Different proportions of cells adjacent to sieve elements become infected in different plant species. This appears to be related to how well viral gene products interact with specific hosts. CTV has three genes (p33, p18, and p13) that are not necessary for infection of most of its hosts, but are needed in different combinations for infection of certain citrus species. These genes apparently were acquired by the virus to extend its host range. Some specific viral gene products have been implicated in symptom induction. Remarkably, the deletion of these genes from the virus genome can induce large increases in stem pitting (SP) symptoms. The p23 gene, which is a suppressor of RNA silencing and a regulator of viral RNA synthesis, has been shown to be the cause of seedling yellows (SY) symptoms in sour orange. Most isolates of CTV in nature are populations of different strains of CTV. The next frontier of CTV biology is the understanding how the virus

  18. Citrus tristeza virus-host interactions.

    Science.gov (United States)

    Dawson, W O; Garnsey, S M; Tatineni, S; Folimonova, S Y; Harper, S J; Gowda, S

    2013-01-01

    Citrus tristeza virus (CTV) is a phloem-limited virus whose natural host range is restricted to citrus and related species. Although the virus has killed millions of trees, almost destroying whole industries, and continually limits production in many citrus growing areas, most isolates are mild or symptomless in most of their host range. There is little understanding of how the virus causes severe disease in some citrus and none in others. Movement and distribution of CTV differs considerably from that of well-studied viruses of herbaceous plants where movement occurs largely through adjacent cells. In contrast, CTV systemically infects plants mainly by long-distance movement with only limited cell-to-cell movement. The virus is transported through sieve elements and occasionally enters an adjacent companion or phloem parenchyma cell where virus replication occurs. In some plants this is followed by cell-to-cell movement into only a small cluster of adjacent cells, while in others there is no cell-to-cell movement. Different proportions of cells adjacent to sieve elements become infected in different plant species. This appears to be related to how well viral gene products interact with specific hosts. CTV has three genes (p33, p18, and p13) that are not necessary for infection of most of its hosts, but are needed in different combinations for infection of certain citrus species. These genes apparently were acquired by the virus to extend its host range. Some specific viral gene products have been implicated in symptom induction. Remarkably, the deletion of these genes from the virus genome can induce large increases in stem pitting (SP) symptoms. The p23 gene, which is a suppressor of RNA silencing and a regulator of viral RNA synthesis, has been shown to be the cause of seedling yellows (SY) symptoms in sour orange. Most isolates of CTV in nature are populations of different strains of CTV. The next frontier of CTV biology is the understanding how the virus

  19. Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration.

    Directory of Open Access Journals (Sweden)

    Irena Zurnic

    2016-08-01

    Full Text Available Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H screen with prototype FV (PFV Gag protein as bait we identified human polo-like kinase 2 (hPLK2, a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells.

  20. Olfactory host location in beetle bruchid parasitoid Dinarmus basalis ...

    African Journals Online (AJOL)

    Hymenoptera : Pteromalidae). O Rabi, AD Bouli, JP Monge. Abstract. The role of chemicals cues in host location by the parasitoid Dinarmus basalis (Rond.) was investigated in bioassays by measuring response to stimuli associated with one of its hosts, ...

  1. Host plant quality mediates competition between arbuscular mycorrhizal fungi

    NARCIS (Netherlands)

    Knegt, B.; Jansa, J.; Franken, O.; Engelmoer, D.J.P.; Werner, G.D.A.; Bücking, H.; Kiers, E.T.

    2016-01-01

    Arbuscular mycorrhizal fungi exchange soil nutrients for carbon from plant hosts. Empirical works suggests that hosts may selectively provide resources to different fungal species, ultimately affecting fungal competition. However, fungal competition may also be mediated by colonization strategies of

  2. From Many Hosts, One Accidental Pathogen: The Diverse Protozoan Hosts of Legionella

    Directory of Open Access Journals (Sweden)

    David K. Boamah

    2017-11-01

    Full Text Available The 1976 outbreak of Legionnaires' disease led to the discovery of the intracellular bacterial pathogen Legionella pneumophila. Given their impact on human health, Legionella species and the mechanisms responsible for their replication within host cells are often studied in alveolar macrophages, the primary human cell type associated with disease. Despite the potential severity of individual cases of disease, Legionella are not spread from person-to-person. Thus, from the pathogen's perspective, interactions with human cells are accidents of time and space—evolutionary dead ends with no impact on Legionella's long-term survival or pathogenic trajectory. To understand Legionella as a pathogen is to understand its interaction with its natural hosts: the polyphyletic protozoa, a group of unicellular eukaryotes with a staggering amount of evolutionary diversity. While much remains to be understood about these enigmatic hosts, we summarize the current state of knowledge concerning Legionella's natural host range, the diversity of Legionella-protozoa interactions, the factors influencing these interactions, the importance of avoiding the generalization of protozoan-bacterial interactions based on a limited number of model hosts and the central role of protozoa to the biology, evolution, and persistence of Legionella in the environment.

  3. Hijacking host cell highways: manipulation of the host actin cytoskeleton by obligate intracellular bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Punsiri M Colonne

    2016-09-01

    Full Text Available Intracellular bacterial pathogens replicate within eukaryotic cells and display unique adaptations that support key infection events including invasion, replication, immune evasion, and dissemination. From invasion to dissemination, all stages of the intracellular bacterial life cycle share the same three-dimensional cytosolic space containing the host cytoskeleton. For successful infection and replication, many pathogens hijack the cytoskeleton using effector proteins introduced into the host cytosol by specialized secretion systems. A subset of effectors contains eukaryotic-like motifs that mimic host proteins to exploit signaling and modify specific cytoskeletal components such as actin and microtubules. Cytoskeletal rearrangement promotes numerous events that are beneficial to the pathogen, including internalization of bacteria, subversion of cell intrinsic immunity, structural support for bacteria-containing vacuoles, altered vesicular trafficking, actin-dependent bacterial movement, and pathogen dissemination. This review highlights a diverse group of obligate intracellular bacterial pathogens that manipulate the host cytoskeleton to thrive within eukaryotic cells and discusses underlying molecular mechanisms that promote these dynamic host-pathogen interactions.

  4. An Endoparasitoid Avoids Hyperparasitism by Manipulating Immobile Host Herbivore to Modify Host Plant Morphology

    Science.gov (United States)

    Fujii, Tomohisa; Matsuo, Kazunori; Abe, Yoshihisa; Yukawa, Junichi; Tokuda, Makoto

    2014-01-01

    Many parasitic organisms have an ability to manipulate their hosts to increase their own fitness. In parasitoids, behavioral changes of mobile hosts to avoid or protect against predation and hyperparasitism have been intensively studied, but host manipulation by parasitoids associated with endophytic or immobile hosts has seldom been investigated. We examined the interactions between a gall inducer Masakimyia pustulae (Diptera: Cecidomyiidae) and its parasitoids. This gall midge induces dimorphic leaf galls, thick and thin types, on Euonymus japonicus (Celastraceae). Platygaster sp. was the most common primary parasitoid of M. pustulae. In galls attacked by Platygaster sp., whole gall thickness as well as thicknesses of upper and lower gall wall was significantly larger than unparasitized galls, regardless of the gall types, in many localities. In addition, localities and tree individuals significantly affected the thickness of gall. Galls attacked by Platygaster sp. were seldom hyperparasitized in the two gall types. These results strongly suggest that Platygaster sp. manipulates the host plant's development to avoid hyperparasitism by thickening galls. PMID:25033216

  5. Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

    Science.gov (United States)

    Johnson, Timothy J.; Ricke, Steven C.; Nayak, Rajesh; Danzeisen, Jessica

    2013-01-01

    SUMMARY Enteric pathogens such as Salmonella enterica cause significant morbidity and mortality. S. enterica serovars are a diverse group of pathogens that have evolved to survive in a wide range of environments and across multiple hosts. S. enterica serovars such as S. Typhi, S. Dublin, and S. Gallinarum have a restricted host range, in which they are typically associated with one or a few host species, while S. Enteritidis and S. Typhimurium have broad host ranges. This review examines how S. enterica has evolved through adaptation to different host environments, especially as related to the chicken host, and continues to be an important human pathogen. Several factors impact host range, and these include the acquisition of genes via horizontal gene transfer with plasmids, transposons, and phages, which can potentially expand host range, and the loss of genes or their function, which would reduce the range of hosts that the organism can infect. S. Gallinarum, with a limited host range, has a large number of pseudogenes in its genome compared to broader-host-range serovars. S. enterica serovars such as S. Kentucky and S. Heidelberg also often have plasmids that may help them colonize poultry more efficiently. The ability to colonize different hosts also involves interactions with the host's immune system and commensal organisms that are present. Thus, the factors that impact the ability of Salmonella to colonize a particular host species, such as chickens, are complex and multifactorial, involving the host, the pathogen, and extrinsic pressures. It is the interplay of these factors which leads to the differences in host ranges that we observe today. PMID:24296573

  6. Evolution of host specificity in monogeneans parasitizing African cichlid fish.

    Science.gov (United States)

    Mendlová, Monika; Šimková, Andrea

    2014-02-14

    The patterns and processes linked to the host specificity of parasites represent one of the central themes in the study of host-parasite interactions. We investigated the evolution and determinants of host specificity in gill monogeneans of Cichlidogyrus and Scutogyrus species parasitizing African freshwater fish of Cichlidae. We analyzed (1) the link between host specificity and parasite phylogeny, (2) potential morphometric correlates of host specificity (i.e. parasite body size and the morphometrics of the attachment apparatus), and (3) potential determinants of host specificity following the hypothesis of ecological specialization and the hypothesis of specialization on predictable resources (i.e. host body size and longevity were considered as measures of host predictability), and (4) the role of brooding behavior of cichlids in Cichlidogyrus and Scutogyrus diversification. No significant relationships were found between host specificity and phylogeny of Cichlidogyrus and Scutogyrus species. The mapping of host specificity onto the parasite phylogenetic tree revealed that an intermediate specialist parasitizing congeneric cichlid hosts represents the ancestral state for the Cichlidogyrus/Scutogyrus group. Only a weak relationship was found between the morphometry of the parasites' attachment apparatus and host specificity. Our study did not support the specialization on predictable resources or ecological specialization hypotheses. Nevertheless, host specificity was significantly related to fish phylogeny and form of parental care. Our results confirm that host specificity is not a derived condition for Cichlidogyrus/Scutogyrus parasites and may reflect other than historical constraints. Attachment apparatus morphometry reflects only partially (if at all) parasite adaptation to the host species, probably because of the morphological similarity of rapidly evolved cichlids (analyzed in our study). However, we showed that parental care behavior of cichlids may

  7. HOST GALAXIES AS GAMMA-RAY BURST DISTANCE INDICATORS

    Energy Technology Data Exchange (ETDEWEB)

    D. BAND; ET AL

    2001-01-01

    We calculate the distributions of the total burst energy, the peak luminosity and the X-ray afterglow energy using burst observations and distances to the associated host galaxies. To expand the sample, we include redshift estimates for host galaxies without spectroscopic redshifts. The methodology requires a model of the host galaxy population; we find that in the best model the burst rate is proportional to the host galaxy luminosity at the time of the burst.

  8. ALMA Examines a Distant Quasar Host

    Science.gov (United States)

    Kohler, Susanna

    2017-04-01

    The dust continuum (top) and the [CII] emission (bottom) maps for the region around J1120+0641. [Adapted from Venemans et al. 2017]A team of scientists has used the Atacama Large Millimeter/submillimeter Array (ALMA) to explore the host galaxy of the most distant quasar known. Their observations may help us to build a picture of how the first supermassive black holes in the universe formed and evolved.Faraway Monsters and Their GalaxiesWe know that quasars the incredibly luminous and active centers of some distant galaxies are powered by accreting, supermassive black holes. These monstrous powerhouses have been detected out to redshifts of z 7, when the universe was younger than a billion years old.Though weve observed over a hundred quasars at high redshift, we still dont understand how these early supermassive black holes formed, or whether the black holes and the galaxies that host them co-evolved. In order to answer questions like these, however, we first need to gather information about the properties and behavior of various supermassive black holes and their host galaxies.A team of scientists led by Bram Venemans (Max-Planck Institute for Astronomy, Germany) recently used the unprecedented sensitivity and angular resolution of ALMA as well as the Very Large Array and the IRAM Plateau de Bure Interferometer to examine the most distant quasar currently known, J1120+0641, located at a redshift of z = 7.1.A High-Resolution LookThe teams observations of the dust and gas emission from the quasars host galaxy revealed a number of intriguing things:The red and blue sides of the [CII] emission line are shown here as contours, demonstrating that theres no ordered rotational motion of the gas on kpc scales. [Adapted from Venemans et al. 2017]The majority of the galaxys emission is very compact. Around 80% of the observed flux came from a region of only 11.5 kpc in diameter.Despite the fact that the 2.4-billion-solar-mass black hole at the galaxys center is accreting at

  9. Cross-Regulation between Transposable Elements and Host DNA Replication.

    Science.gov (United States)

    Zaratiegui, Mikel

    2017-03-21

    Transposable elements subvert host cellular functions to ensure their survival. Their interaction with the host DNA replication machinery indicates that selective pressures lead them to develop ancestral and convergent evolutionary adaptations aimed at conserved features of this fundamental process. These interactions can shape the co-evolution of the transposons and their hosts.

  10. Immunoregulation by Trichinella spiralis: Benefits for parasite and host

    NARCIS (Netherlands)

    Aranzamendi Esteban, C.R.|info:eu-repo/dai/nl/341157430

    2013-01-01

    Several studies indicate that certain helminths suppress the host immune responses. This suppression may benefit the parasite since it increases the chances of survival in their host. By doing so, the hosts may also benefit due to concomitant reduction of immune pathology associated with allergies

  11. Reviewing host proteins of Rhabdoviridae: Possible leads for lesser ...

    Indian Academy of Sciences (India)

    Rhabdoviridae, characterized by bullet-shaped viruses, is known for its diverse host range, which includes plants, arthropods, fishes and humans. Understanding the viral–host interactions of this family can prove beneficial in developing effective therapeutic strategies. The host proteins interacting with animal rhabdoviruses ...

  12. Co-niche construction between hosts and symbionts: ideas and ...

    Indian Academy of Sciences (India)

    2017-07-05

    Jul 5, 2017 ... Symbiosis is a process that can generate evolutionary novelties and can extend the phenotypic niche space of organisms. Symbionts can act together with their hosts to co-construct host organs, within which symbionts are housed. Once established within hosts, symbionts can also influence various ...

  13. Evolution in action : host race formation in Galerucella nymphaeae

    NARCIS (Netherlands)

    Pappers, Stephanie Maria

    2001-01-01

    A host race is a population which is partially reproductively isolated as a direct consequence of adaptation to a certain host. For host race formation to occur five conditions should be met. First of all, the populations should occur in sympatry, which means that they co-occur within the normal

  14. Compositional discordance between prokaryotic plasmids and host chromosomes

    Directory of Open Access Journals (Sweden)

    van Kampen Antoine HC

    2006-02-01

    Full Text Available Abstract Background Most plasmids depend on the host replication machinery and possess partitioning genes. These properties confine plasmids to a limited range of hosts, yielding a close and presumably stable relationship between plasmid and host. Hence, it is anticipated that due to amelioration the dinucleotide composition of plasmids is similar to that of the genome of their hosts. However, plasmids are also thought to play a major role in horizontal gene transfer and thus are frequently exchanged between hosts, suggesting dinucleotide composition dissimilarity between plasmid and host genome. We compared the dinucleotide composition of a large collection of plasmids with that of their host genomes to shed more light on this enigma. Results The dinucleotide frequency, coined the genome signature, facilitates the identification of putative horizontally transferred DNA in complete genome sequences, since it was found to be typical for a certain genome, and similar between related species. By comparison of the genome signature of 230 plasmid sequences with that of the genome of each respective host, we found that in general the genome signature of plasmids is dissimilar from that of their host genome. Conclusion Our results show that the genome signature of plasmids does not resemble that of their host genome. This indicates either absence of amelioration or a less stable relationship between plasmids and their host. We propose an indiscriminate lifestyle for plasmids preserving the genome signature discordance between these episomes and host chromosomes.

  15. Temperature alters host genotype-specific susceptibility to chytrid infection

    NARCIS (Netherlands)

    Gsell, A.S.; De Senerpont Domis, L.N.; Van Donk, E.; Ibelings, B.W.

    2013-01-01

    The cost of parasitism often depends on environmental conditions and host identity. Therefore, variation in the biotic and abiotic environment can have repercussions on both, species-level host-parasite interaction patterns but also on host genotype-specific susceptibility to disease. We exposed

  16. High power laser having a trivalent liquid host

    Science.gov (United States)

    Ault, Earl R.

    2005-08-16

    A laser having a lasing chamber and a semiconductor pumping device with trivalent titanium ions dissolved in a liquid host within the lasing chamber. Since the host is a liquid, it can be removed from the optical cavity when it becomes heated avoiding the inevitable optical distortion and birefringence common to glass and crystal hosts.

  17. Statistical Properties of Gamma-Ray Burst Host Galaxies

    Indian Academy of Sciences (India)

    A statistical analysis of gamma-ray burst host galaxies is presented and a clear metallicity-stellar mass relation is found in our sample. A trend that a more massive host galaxy tends to have a higher star-formation rate is also found. No correlation is found between V and H. GRB host galaxies at a higher redshift also tend ...

  18. Parasite transmission in social interacting hosts: Monogenean epidemics in guppies

    Science.gov (United States)

    Johnson, Mirelle B.; Lafferty, Kevin D.; van Oosterhout, Cock; Cable, Joanne

    2011-01-01

    Background Infection incidence increases with the average number of contacts between susceptible and infected individuals. Contact rates are normally assumed to increase linearly with host density. However, social species seek out each other at low density and saturate their contact rates at high densities. Although predicting epidemic behaviour requires knowing how contact rates scale with host density, few empirical studies have investigated the effect of host density. Also, most theory assumes each host has an equal probability of transmitting parasites, even though individual parasite load and infection duration can vary. To our knowledge, the relative importance of characteristics of the primary infected host vs. the susceptible population has never been tested experimentally. Methodology/Principal Findings Here, we examine epidemics using a common ectoparasite, Gyrodactylus turnbulli infecting its guppy host (Poecilia reticulata). Hosts were maintained at different densities (3, 6, 12 and 24 fish in 40 L aquaria), and we monitored gyrodactylids both at a population and individual host level. Although parasite population size increased with host density, the probability of an epidemic did not. Epidemics were more likely when the primary infected fish had a high mean intensity and duration of infection. Epidemics only occurred if the primary infected host experienced more than 23 worm days. Female guppies contracted infections sooner than males, probably because females have a higher propensity for shoaling. Conclusions/Significance These findings suggest that in social hosts like guppies, the frequency of social contact largely governs disease epidemics independent of host density.

  19. Parasite transmission in social interacting hosts: monogenean epidemics in guppies.

    Directory of Open Access Journals (Sweden)

    Mirelle B Johnson

    Full Text Available BACKGROUND: Infection incidence increases with the average number of contacts between susceptible and infected individuals. Contact rates are normally assumed to increase linearly with host density. However, social species seek out each other at low density and saturate their contact rates at high densities. Although predicting epidemic behaviour requires knowing how contact rates scale with host density, few empirical studies have investigated the effect of host density. Also, most theory assumes each host has an equal probability of transmitting parasites, even though individual parasite load and infection duration can vary. To our knowledge, the relative importance of characteristics of the primary infected host vs. the susceptible population has never been tested experimentally. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine epidemics using a common ectoparasite, Gyrodactylus turnbulli infecting its guppy host (Poecilia reticulata. Hosts were maintained at different densities (3, 6, 12 and 24 fish in 40 L aquaria, and we monitored gyrodactylids both at a population and individual host level. Although parasite population size increased with host density, the probability of an epidemic did not. Epidemics were more likely when the primary infected fish had a high mean intensity and duration of infection. Epidemics only occurred if the primary infected host experienced more than 23 worm days. Female guppies contracted infections sooner than males, probably because females have a higher propensity for shoaling. CONCLUSIONS/SIGNIFICANCE: These findings suggest that in social hosts like guppies, the frequency of social contact largely governs disease epidemics independent of host density.

  20. Epigenetic modulation of host: new insights into immune evasion by ...

    Indian Academy of Sciences (India)

    Viruses have evolved with their hosts, which include all living species. This has been partly responsible for the development of highly advanced immune systems in the hosts. However, viruses too have evolved ways to regulate and evade the host's immune defence. In addition to mutational mechanisms that viruses employ ...

  1. Compositional discordance between prokaryotic plasmids and host chromosomes

    NARCIS (Netherlands)

    van Passel, M.W.J.; Bart, A.; Luyf, A.C.M.; van Kampen, A.H.C.; van der Ende, A.

    2006-01-01

    Background: Most plasmids depend on the host replication machinery and possess partitioning genes. These properties confine plasmids to a limited range of hosts, yielding a close and presumably stable relationship between plasmid and host. Hence, it is anticipated that due to amelioration the

  2. Cryptosporidium parvum Infection Requires Host Cell Actin Polymerization

    OpenAIRE

    Elliott, David A.; Coleman, Daniel J.; Lane, Michael A.; May, Robin C.; Machesky, Laura M.; Clark, Douglas P.

    2001-01-01

    The intracellular protozoan parasite Cryptosporidium parvum accumulates host cell actin at the interface between the parasite and the host cell cytoplasm. Here we show that the actin polymerizing proteins Arp2/3, vasodilator-stimulated phosphoprotein (VASP), and neural Wiskott Aldrich syndrome protein (N-WASP) are present at this interface and that host cell actin polymerization is necessary for parasite infection.

  3. Cryptosporidium parvum infection requires host cell actin polymerization.

    Science.gov (United States)

    Elliott, D A; Coleman, D J; Lane, M A; May, R C; Machesky, L M; Clark, D P

    2001-09-01

    The intracellular protozoan parasite Cryptosporidium parvum accumulates host cell actin at the interface between the parasite and the host cell cytoplasm. Here we show that the actin polymerizing proteins Arp2/3, vasodilator-stimulated phosphoprotein (VASP), and neural Wiskott Aldrich syndrome protein (N-WASP) are present at this interface and that host cell actin polymerization is necessary for parasite infection.

  4. MORPHOLOGY OF METHANE HYDRATE HOST SEDIMENTS.

    Energy Technology Data Exchange (ETDEWEB)

    JONES,K.W.; FENG,H.; TOMOV,S.; WINTER,W.J.; EATON,M.; MAHAJAN,D.

    2004-12-01

    Results from simulated experiments in several laboratories show that host sediments influence hydrate formation in accord with known heterogeneity of host sediments at sites of gas hydrate occurrence (1). For example, in Mackenzie Delta, NWT Canada (Mallik 2L-38 well), coarser-grained units (pore-filling model) are found whereas in the Gulf of Mexico, the found hydrate samples do not appear to be lithologically controlled. We have initiated a systematic study of sediments, initially focusing on samples from various depths at a specific site, to establish a correlation with hydrate occurrence (or variations thereof) to establish differences in their microstructure, porosity, and other associated properties. The synchrotron computed microtomography (CMT) set-up at the X-27A tomography beam line at the National Synchrotron Light Source (NSLS), Brookhaven National Laboratory was used as a tool to study sediments from Blake Ridge at three sub bottom depths of 0.2, 50, and 667 meters. Results from the tomographic analysis of the deepest sample (667 m) are presented here to illustrate how tomography can be used to obtain new insights into the structures of methane hydrate host sediments. The investigation shows the internal grain/pore space resolution in the microstructure and a 3-D visualization of the connecting pathways obtained following data segmentation into pore space and grains within the sediment sample. The analysis gives the sample porosity, specific surface area, mean particle size, and tortuosity, as well. An earlier report on the experimental program has been given by Mahajan et al. (2).

  5. Host-pathogen interaction in invasive Salmonellosis.

    Directory of Open Access Journals (Sweden)

    Hanna K de Jong

    Full Text Available Salmonella enterica infections result in diverse clinical manifestations. Typhoid fever, caused by S. enterica serovar Typhi (S. Typhi and S. Paratyphi A, is a bacteremic illness but whose clinical features differ from other Gram-negative bacteremias. Non-typhoidal Salmonella (NTS serovars cause self-limiting diarrhea with occasional secondary bacteremia. Primary NTS bacteremia can occur in the immunocompromised host and infants in sub-Saharan Africa. Recent studies on host-pathogen interactions in Salmonellosis using genome sequencing, murine models, and patient studies have provided new insights. The full genome sequences of numerous S. enterica serovars have been determined. The S. Typhi genome, compared to that of S. Typhimurium, harbors many inactivated or disrupted genes. This can partly explain the different immune responses both serovars induce upon entering their host. Similar genome degradation is also observed in the ST313 S. Typhimurium strain implicated in invasive infection in sub-Saharan Africa. Virulence factors, most notably, type III secretion systems, Vi antigen, lipopolysaccharide and other surface polysaccharides, flagella, and various factors essential for the intracellular life cycle of S. enterica have been characterized. Genes for these factors are commonly carried on Salmonella Pathogenicity Islands (SPIs. Plasmids also carry putative virulence-associated genes as well as those responsible for antimicrobial resistance. The interaction of Salmonella pathogen-associated molecular patterns (PAMPs with Toll-like receptors (TLRs and NOD-like receptors (NLRs leads to inflammasome formation, activation, and recruitment of neutrophils and macrophages and the production of pro-inflammatory cytokines, most notably interleukin (IL-6, IL-1β, tumor necrosis factor (TNF-α, and interferon-gamma (IFN-γ. The gut microbiome may be an important modulator of this immune response. S. Typhimurium usually causes a local intestinal immune

  6. Prokaryotes versus Eukaryotes: Who is hosting whom?

    Directory of Open Access Journals (Sweden)

    Guillermo eTellez

    2014-10-01

    Full Text Available Microorganisms represent the largest component of biodiversity in our world. For millions of years, prokaryotic microorganisms have functioned as a major selective force shaping eukaryotic evolution. Microbes that live inside and on animals outnumber the animals’ actual somatic and germ cells by an estimated 10-fold. Collectively, the intestinal microbiome represents a ‘forgotten organ’, functioning as an organ inside another that can execute many physiological responsibilities. The nature of primitive eukaryotes was drastically changed due to the association with symbiotic prokaryotes facilitating mutual coevolution of host and microbe. Phytophagous insects have long been used to test theories of evolutionary diversification; moreover, the diversification of a number of phytophagous insect lineages has been linked to mutualisms with microbes. From termites and honey bees to ruminants and mammals, depending on novel biochemistries provided by the prokaryotic microbiome, the association helps to metabolize several nutrients that the host cannot digest and converting these into useful end products (such as short chain fatty acids, a process which has huge impact on the biology and homeostasis of metazoans. More importantly, in a direct and/or indirect way, the intestinal microbiota influences the assembly of gut-associated lymphoid tissue, helps to educate immune system, affects the integrity of the intestinal mucosal barrier, modulates proliferation and differentiation of its epithelial lineages, regulates angiogenesis, and modifies the activity of enteric as well as the central nervous system,. Despite these important effects, the mechanisms by which the gut microbial community influences the host’s biology remains almost entirely unknown. Our aim here is to encourage empirical inquiry into the relationship between mutualism and evolutionary diversification between prokaryotes and eukaryotes which encourage us to postulate: Who is

  7. Novel host materials for blue phosphorescent OLEDs

    Science.gov (United States)

    Strohriegl, Peter; Wagner, Daniel; Schrögel, Pamela; Hoffmann, Sebastian T.; Köhler, Anna; Heinemeyer, Ute; Münster, Ingo

    2013-09-01

    We present two classes of host materials for blue phosphors. The first are carbazole substituted biphenyls 1-9. In these CBP-type materials the triplets are confined to one half of the molecules by using either twisted biphenyls or by a metalinkage of the carbazoles to the biphenyl. We obtained high triplet energies of 2.95-2.98 eV and high glass transition temperatures in the range of 100-120 °C. OLEDs were fabricated using the host material 6 and the carbene emitter Ir(dbfmi) with pure blue emission at 450 nm. The devices achieved an external quantum efficiency of 8.7% at 100 cd/m2 and 6.1% at 1000 cd/m2. MBPTRZ with an electron transporting biscarbazolyltriazine that is separated from the hole transporting carbazole by a non-conjugated, meta-linked biphenyl unit is an example for a bipolar matrix material. The excellent glass forming properties and the high Tg of 132 °C ensure morphological stability in OLEDs. The meta-linkage and the additional twist at the biphenyl unit, which is achieved by two methyl groups in the 2- and 2'-position of the biphenyl in MBPTRZ leads to a decoupling of the electron accepting and electron donating part and therefore to a high triplet energy of 2.81 eV. DFT calculations show a clear separation of the electron and hole transporting moieties. A phosphorescent OLED with MBPTRZ as host and FIrpic as emitter reached a maximum external quantum efficiency of 7.0%, a current efficiency of 16.3 cd/A and a power efficiency of 6.3 lm/W.

  8. Anemonefish oxygenate their anemone hosts at night.

    Science.gov (United States)

    Szczebak, Joseph T; Henry, Raymond P; Al-Horani, Fuad A; Chadwick, Nanette E

    2013-03-15

    Many stony coral-dwelling fishes exhibit adaptations to deal with hypoxia among the branches of their hosts; however, no information exists on the respiratory ecophysiology of obligate fish associates of non-coral organisms such as sea anemones and sponges. This study investigated metabolic and behavioral interactions between two-band anemonefish (Amphiprion bicinctus) and bulb-tentacle sea anemones (Entacmaea quadricolor) at night. We measured the net dark oxygen uptake ( , μmol O2 h(-1)) of fish-anemone pairs when partners were separate from each other, together as a unit, and together as a unit but separated by a mesh screen that prevented physical contact. We also measured the effects of water current on sea anemone and quantified the nocturnal behaviors of fish in the absence and presence of host anemones in order to discern the impacts of anemone presence on fish behavior. Net of united pairs was significantly higher than that of both separated pairs and united pairs that were separated by a mesh screen. Anemone increased with flow rate from 0.5 to 2.0 cm s(-1), after which remained constant up to a water flow rate of 8.0 cm s(-1). Furthermore, the percentage time and bout frequency of flow-modulating behaviors by fish increased significantly when anemones were present. We conclude that physical contact between anemonefish and sea anemones elevates the of at least one of the partners at night, and anemonefish behavior at night appears to oxygenate sea anemone hosts and to augment the metabolism of both partners.

  9. Natural invertebrate hosts of iridoviruses (Iridoviridae)

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Trevor [Instituto de Ecologia A.C., Veracruz (Mexico)]. E-mail: trevor.williams@inecol.edu.mx

    2008-11-15

    Invertebrate iridescent viruses (IIVs) are icosahedral DNA viruses that infect invertebrates, mainly insects and terrestrial isopods, in damp and aquatic habitats. Exhaustive searches of databases resulted in the identification of 79 articles reporting 108 invertebrate species naturally infected by confirmed or putative iridoviruses. Of these, 103 (95%) were arthropods and the remainder were molluscs, an annelid worm and a nematode. Nine species were from marine habitats. Of the 99 non-marine species, 49 were from terrestrial habitats and 50 were aquatic, especially the aquatic stages of Diptera (44 species). The abundance of records from species of Aedes, Ochlerotatus and Psorophora contrasts markedly with a paucity of records from species of Anopheles, Culex and Culiseta. Records from terrestrial isopods are numerous (19 species), although the diversity of IIVs that infect them is mostly unstudied. IIV infections have been reported from every continent, except Antarctica, but there are few records from Africa, southern Asia and Latin America. Most reports describe patent IIV infections as rare whereas inapparent (covert) infection may be common in certain species. The relationship between particle size and iridescent colour of the host is found to be consistent with optical theory in the great majority of cases. Only 24 reported IIVs from insect hosts have partial characterization data and only two have been subjected to complete genome sequencing. I show that the rate of publication on IIVs has slowed from 1990 to the present, and I draw a number of conclusions and suggestions from the host list and make recommendations for future research efforts. (author)

  10. Host Materials for Transition-Metal Ions

    Science.gov (United States)

    1989-09-01

    Slater integral shifts as AF(2) -<r2>2S (2 ) and AF(4) = 4<r4>2S(4); the units are such that if <rk> is in angstrom units, theii each shift is in...units of cm-1 . 2.3 Experimental Results For each host we include tables Meorting all the experimental data in terms of the Slater integrals , F ", and...Phys. C14 (1981), L105. 2. D. Babel, R. Haegele, G. Pausewang, and F. Wall, Uber Kubische undI I III Hexagonale Elpasolithe A2B M F6, Mater. Res. Bull

  11. Collaborative web hosting challenges and research directions

    CERN Document Server

    Ahmed, Reaz

    2014-01-01

    This brief presents a peer-to-peer (P2P) web-hosting infrastructure (named pWeb) that can transform networked, home-entertainment devices into lightweight collaborating Web servers for persistently storing and serving multimedia and web content. The issues addressed include ensuring content availability, Plexus routing and indexing, naming schemes, web ID, collaborative web search, network architecture and content indexing. In pWeb, user-generated voluminous multimedia content is proactively uploaded to a nearby network location (preferably within the same LAN or at least, within the same ISP)

  12. Mycobacterium tuberculosis effectors interfering host apoptosis signaling.

    Science.gov (United States)

    Liu, Minqiang; Li, Wu; Xiang, Xiaohong; Xie, Jianping

    2015-07-01

    Tuberculosis remains a serious human public health concern. The coevolution between its pathogen Mycobacterium tuberculosis and human host complicated the way to prevent and cure TB. Apoptosis plays subtle role in this interaction. The pathogen endeavors to manipulate the apoptosis via diverse effectors targeting key signaling nodes. In this paper, we summarized the effectors pathogen used to subvert the apoptosis, such as LpqH, ESAT-6/CFP-10, LAMs. The interplay between different forms of cell deaths, such as apoptosis, autophagy, necrosis, is also discussed with a focus on the modes of action of effectors, and implications for better TB control.

  13. La host (2010) Any XXIII. Núm. 18

    OpenAIRE

    Francisco, José Vicente; Ferrer, Nieves; Martínez, José María; Lauterio, Amàlia; Garzó, Ricardo; Vicente, Ricardo; Barroso, Carmen; Martínez, Ángel; Breva, Juan José; Ferrán, Lledó; Toca, Luís; Gómez, Manuel; García, Agustín; García Cerveró, José Manuel; Torres, Guillermo

    2010-01-01

    Sumari: Salutació.Pregó i Himne de la Host.Privilegi del trasllat.Sopar de Esponsors.Els Alcaids del Castell Vell.Discurs Despedida Alcaid 2009.La Gala dels Alcaids.La nostra Patrona.En Javier Moliner i Gargallo Alcaid 2010.Discurs de l'Alcaid 2010.SUSEGANA (Treviso, Italia).VALENCIA. Capítol Círculo de Enófilos Utiel-Requena.Pernil de Guijuelo.GUIJUELO (Salamanca). XIV Capítol Confraria Gastronomica de Guijuelo.VALDEPEÑAS DE JAÉN (Jaén). I Congrés Andalús de Confraries Enogastronòmiques.LES ...

  14. Cutaneous Graft-Versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Emine Çölgeçen

    2011-12-01

    Full Text Available Hematopoietic stem cell transplantation (SCT, which is being used increasingly day by day; is a treatment method for the management of mainly lymphohematopoietic diseases and also immunological and metabolic disorders. Graft versus host disease (GVHD is a complicated clinical syndrome involving a severe immune reaction mediated by immunologically competent cells, mainly T lymphocytes, resulting in organ dysfunction. It is accepted as the most important cause of mortality and morbidity following SCT. GVHD has also resulted from transfusion of nonirradiated blood products, from maternal-fetal transfusions and following solid organ transplants. In this paper, the clinical manifestations, pathogenesis, histopathology, new classification system and treatment of GVHD is discussed.

  15. Permanence and chaos in a host-parasitoid model with prolonged diapause for the host

    Science.gov (United States)

    Zhao, Min; Zhang, Limin

    2009-12-01

    The dynamic behavior of a host-parasitoid model with prolonged diapause for the host is investigated. It is proved that the system is permanent under certain appropriate conditions. Numerical simulations are presented to illustrate consistency with the theoretical analysis. For the biologically reasonable range of parameter values, the global dynamics of the system have been studied numerically. In particular, the effect of prolonged diapause on the system has been investigated. Many forms of complex dynamics are observed, including quasi-periodicity, period-doubling and period-halving bifurcations, chaotic bands with periodic windows, attractor crises, intermittency, and supertransients. These complex dynamic behaviors are confirmed by the largest Lyapunov exponents.

  16. Host Reproductive Phenology Drives Seasonal Patterns of Host Use in Mosquitoes

    OpenAIRE

    Burkett-Cadena, Nathan D.; McClure, Christopher J. W.; Ligon, Russell A.; Graham, Sean P.; Guyer, Craig; Hill, Geoffrey E.; Ditchkoff, Stephen S.; Eubanks, Micky D.; Hassan, Hassan K.; Unnasch, Thomas R.

    2011-01-01

    Seasonal shifts in host use by mosquitoes from birds to mammals drive the timing and intensity of annual epidemics of mosquito-borne viruses, such as West Nile virus, in North America. The biological mechanism underlying these shifts has been a matter of debate, with hypotheses falling into two camps: (1) the shift is driven by changes in host abundance, or (2) the shift is driven by seasonal changes in the foraging behavior of mosquitoes. Here we explored the idea that seasonal changes in ho...

  17. The membrane fusion step of vaccinia virus entry is cooperatively mediated by multiple viral proteins and host cell components.

    Directory of Open Access Journals (Sweden)

    Jason P Laliberte

    2011-12-01

    Full Text Available For many viruses, one or two proteins allow cell attachment and entry, which occurs through the plasma membrane or following endocytosis at low pH. In contrast, vaccinia virus (VACV enters cells by both neutral and low pH routes; four proteins mediate cell attachment and twelve that are associated in a membrane complex and conserved in all poxviruses are dedicated to entry. The aim of the present study was to determine the roles of cellular and viral proteins in initial stages of entry, specifically fusion of the membranes of the mature virion and cell. For analysis of the role of cellular components, we used well characterized inhibitors and measured binding of a recombinant VACV virion containing Gaussia luciferase fused to a core protein; viral and cellular membrane lipid mixing with a self-quenching fluorescent probe in the virion membrane; and core entry with a recombinant VACV expressing firefly luciferase and electron microscopy. We determined that inhibitors of tyrosine protein kinases, dynamin GTPase and actin dynamics had little effect on binding of virions to cells but impaired membrane fusion, whereas partial cholesterol depletion and inhibitors of endosomal acidification and membrane blebbing had a severe effect at the later stage of core entry. To determine the role of viral proteins, virions lacking individual membrane components were purified from cells infected with members of a panel of ten conditional-lethal inducible mutants. Each of the entry protein-deficient virions had severely reduced infectivity and except for A28, L1 and L5 greatly impaired membrane fusion. In addition, a potent neutralizing L1 monoclonal antibody blocked entry at a post-membrane lipid-mixing step. Taken together, these results suggested a 2-step entry model and implicated an unprecedented number of viral proteins and cellular components involved in signaling and actin rearrangement for initiation of virus-cell membrane fusion during poxvirus entry.

  18. Host switching in a generalist parasitoid: contrasting transient and transgenerational costs associated with novel and original host species

    Science.gov (United States)

    Jones, Thomas S; Bilton, Adam R; Mak, Lorraine; Sait, Steven M

    2015-01-01

    Parasitoids face challenges by switching between host species that influence survival and fitness, determine their role in structuring communities, influence species invasions, and affect their importance as biocontrol agents. In the generalist parasitoid, Venturia canescens (Gravenhorst) (Hymenoptera: Ichneumonidae), we investigated the costs in encapsulation, survival, and body size on juveniles when adult parasitoids switched from their original host, Plodia interpunctella (Hübner) (Lepidotera, Pyralidae) to a novel host, Ephestia kuehniella (Zeller) (Lepidoptera, Pyralidae), over multiple generations. Switching had an initial survival cost for juvenile parasitoids in the novel host, but increased survival occurred within two generations. Conversely, mortality in the original host increased. Body size, a proxy for fecundity, also increased with the number of generations in the novel host species, reflecting adaptation or maternal effects due to the larger size of the novel host, and therefore greater resources available to the developing parasitoid. Switching to a novel host appears to have initial costs for a parasitoid, even when the novel host may be better quality, but the costs rapidly diminish. We predict that the net cost of switching to a novel host for parasitoids will be complex and will depend on the initial reduction in fitness from parasitizing a novel host versus local adaptations against parasitoids in the original host. PMID:25691971

  19. Exchange of hosts: can agaonid fig wasps reproduce successfully in the figs of non-host Ficus?

    Science.gov (United States)

    Yang, Pei; Li, Zongbo; Peng, Yanqiong; Yang, Darong

    2012-03-01

    In the obligate mutualism between figs ( Ficus) and their specific pollinators (Chalcidoidea, Agaonidae), each species of fig wasp typically reproduces in figs of a single host species. Host specificity is maintained largely because pollinators are attracted to tree-specific volatiles released from their host figs, but whether the wasps can reproduce if they enter figs of non-host species is unclear. We investigated the reproductive success of Ceratosolen emarginatus (associated with Ficus auriculata) and Ceratosolen sp. (associated with F. hainanensis) in atypical hosts by experimentally introducing foundresses into host and non-host figs. F. auriculata figs entered by Ceratosolen sp. were more likely to abort than if entered by C. emarginatus, but abortion of F. hainanensis figs was not affected by pollinator species. Single C. emarginatus foundresses produced more but smaller offspring in F. hainanensis than in their normal host. Conversely Ceratosolen sp. produced fewer but larger offspring in F. auriculata than in their normal host, probably as a result of having longer to develop. Mean style length differences, relative to the lengths of the wasps' ovipositors, may have dictated the number of offspring produced, with oviposition made easier by the shorter styles in F. hainanensis figs. Our results imply that, in addition to morphological constraints and tree-specific volatiles, reduced reproductive success in atypical hosts can be another factor maintaining host specificity, but for other species only behavioural changes are required for host switching to occur.

  20. No adaptation of a herbivore to a novel host but loss of adaptation to its native host

    NARCIS (Netherlands)

    Grosman, A.H.; Molina-Rugama, A.J.; Mendes-Dias, R.; Sabelis, M.W.; Menken, S.B.J.; Pallini, A.; Janssen, A.

    2015-01-01

    Most herbivorous arthropods are host specialists and the question is which mechanisms drive the evolution of such specialization. The theory of antagonistic pleiotropy suggests that there is a trade-off between adaptation of herbivores to a novel host and their native host. The mutation accumulation

  1. Host specificity in a diverse Neotropical tick community: an assessment using quantitative network analysis and host phylogeny

    NARCIS (Netherlands)

    Esser, Helen; Herre, Edward A.; Blüthgen, Nico; Loaiza, Jose R.; Bermúdez, Sergio E.; Jansen, P.A.

    2016-01-01

    Background: Host specificity is a fundamental determinant of tick population and pathogen transmission dynamics, and therefore has important implications for human health. Tick host specificity is expected to be particularly high in the tropics, where communities of ticks, hosts and pathogens are

  2. Development of the solitary endoparasitoid Microplitis demolitor: host quality does not increase with host age and size

    NARCIS (Netherlands)

    Harvey, J.A.; Bezemer, T.M.; Elzinga, J.A.; Strand, M.R.

    2004-01-01

    1. Many studies examining the relationship between host size, an index of host quality, and parasitoid fitness use development time and/or adult parasitoid size as currencies of fitness, while ignoring pre-adult mortality. Because the physiological suitability of the host may vary in different

  3. Host adaptive immunity alters gut microbiota.

    Science.gov (United States)

    Zhang, Husen; Sparks, Joshua B; Karyala, Saikumar V; Settlage, Robert; Luo, Xin M

    2015-03-01

    It has long been recognized that the mammalian gut microbiota has a role in the development and activation of the host immune system. Much less is known on how host immunity regulates the gut microbiota. Here we investigated the role of adaptive immunity on the mouse distal gut microbial composition by sequencing 16 S rRNA genes from microbiota of immunodeficient Rag1(-/-) mice, versus wild-type mice, under the same housing environment. To detect possible interactions among immunological status, age and variability from anatomical sites, we analyzed samples from the cecum, colon, colonic mucus and feces before and after weaning. High-throughput sequencing showed that Firmicutes, Bacteroidetes and Verrucomicrobia dominated mouse gut bacterial communities. Rag1(-) mice had a distinct microbiota that was phylogenetically different from wild-type mice. In particular, the bacterium Akkermansia muciniphila was highly enriched in Rag1(-/-) mice compared with the wild type. This enrichment was suppressed when Rag1(-/-) mice received bone marrows from wild-type mice. The microbial community diversity increased with age, albeit the magnitude depended on Rag1 status. In addition, Rag1(-/-) mice had a higher gain in microbiota richness and evenness with increase in age compared with wild-type mice, possibly due to the lack of pressure from the adaptive immune system. Our results suggest that adaptive immunity has a pervasive role in regulating gut microbiota's composition and diversity.

  4. Inhibition of histone binding by supramolecular hosts

    Science.gov (United States)

    Allen, Hillary F.; Daze, Kevin D.; Shimbo, Takashi; Lai, Anne; Musselman, Catherine A.; Sims, Jennifer K.; Wade, Paul A.; Hof†, Fraser; Kutateladze, Tatiana G.

    2015-01-01

    The tandem PHD (plant homeodomain) fingers of the CHD4 (chromodomain helicase DNA-binding protein 4) ATPase are epigenetic readers that bind either unmodified histone H3 tails or H3K9me3 (histone H3 trimethylated at Lys9). This dual function is necessary for the transcriptional and chromatin remodelling activities of the NuRD (nucleosome remodelling and deacetylase) complex. In the present paper, we show that calixarene-based supramolecular hosts disrupt binding of the CHD4 PHD2 finger to H3K9me3, but do not affect the interaction of this protein with the H3K9me0 (unmodified histone H3) tail. A similar inhibitory effect, observed for the association of chromodomain of HP1γ (heterochromatin protein 1γ) with H3K9me3, points to a general mechanism of methyl-lysine caging by calixarenes and suggests a high potential for these compounds in biochemical applications. Immunofluorescence analysis reveals that the supramolecular agents induce changes in chromatin organization that are consistent with their binding to and disruption of H3K9me3 sites in living cells. The results of the present study suggest that the aromatic macrocyclic hosts can be used as a powerful new tool for characterizing methylation-driven epigenetic mechanisms. PMID:24576085

  5. The Statistical Properties of Host Load

    Directory of Open Access Journals (Sweden)

    Peter A. Dinda

    1999-01-01

    Full Text Available Understanding how host load changes over time is instrumental in predicting the execution time of tasks or jobs, such as in dynamic load balancing and distributed soft real‐time systems. To improve this understanding, we collected week‐long, 1 Hz resolution traces of the Digital Unix 5 second exponential load average on over 35 different machines including production and research cluster machines, compute servers, and desktop workstations. Separate sets of traces were collected at two different times of the year. The traces capture all of the dynamic load information available to user‐level programs on these machines. We present a detailed statistical analysis of these traces here, including summary statistics, distributions, and time series analysis results. Two significant new results are that load is self‐similar and that it displays epochal behavior. All of the traces exhibit a high degree of self‐similarity with Hurst parameters ranging from 0.73 to 0.99, strongly biased toward the top of that range. The traces also display epochal behavior in that the local frequency content of the load signal remains quite stable for long periods of time (150–450 s mean and changes abruptly at epoch boundaries. Despite these complex behaviors, we have found that relatively simple linear models are sufficient for short‐range host load prediction.

  6. Tricholoma vaccinum host communication during ectomycorrhiza formation.

    Science.gov (United States)

    Wagner, Katharina; Linde, Jörg; Krause, Katrin; Gube, Matthias; Koestler, Tina; Sammer, Dominik; Kniemeyer, Olaf; Kothe, Erika

    2015-11-01

    The genome sequence of Tricholoma vaccinum was obtained to predict its secretome in order to elucidate communication of T. vaccinum with its host tree spruce (Picea abies) in interkingdom signaling. The most prominent protein domains within the 206 predicted secreted proteins belong to energy and nutrition (52%), cell wall degradation (19%) and mycorrhiza establishment (9%). Additionally, we found small secreted proteins that show typical features of effectors potentially involved in host communication. From the secretome, 22 proteins could be identified, two of which showed higher protein abundances after spruce root exudate exposure, while five were downregulated in this treatment. The changes in T. vaccinum protein excretion with first recognition of the partner were used to identify small secreted proteins with the potential to act as effectors in the mutually beneficial symbiosis. Our observations support the hypothesis of a complex communication network including a cocktail of communication molecules induced long before physical contact of the partners. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Ingestion of host immunoglobulin by Sarcoptes scabiei

    Directory of Open Access Journals (Sweden)

    Simson Tarigan

    2005-03-01

    Full Text Available Scabies is one of the most important diseases in human and veterinary medicine. The available control measures that rely on acaricides are unsustainable, costly and environmentally unfriendly. Vaccination which is supposedly the most attractive alternative control, is sustainable, potentially cheap and environmentally friendly. Recent development in protein biochemistry and recombinant technology have facilitated the development of anti-parasite vaccine which in the past was impossible. One prerequisite for the anti-parasite-vaccine development is that the parasite has to ingest its host immunoglobulin. This study, therefore, was designed to determine whether Sarcoptes scabiei, a non blood-feeding parasite that resides on the avascular cornified layer of the skin, ingest its host immunoglobulin. Sections of routinely processed mites and skin from a mangy goat were probed with peroxidase-conjugated-anti-goat IgG and the immune complex was visualised with diaminobenzidine solution. To determine whether the ingested IgG was still intact or had been fragmented by the proteolytic enzymes, immunoblotting analysis of SDS-PAGE- fractionated proteins extracted from washed mites was performed. Quantification of IgG was done byan Elisa using purified goat IgG as control. This study showed that IgG in the mites confined to the mite’s gut only, and only a fraction of mite population ingested the IgG. The ingested IgG, as shown by immunoblot analysis, was mostly still intact. This study indicates that development of anti-scabies vaccines is reasonable.

  8. Patterns of host adaptation in fly infecting Entomophthora species

    DEFF Research Database (Denmark)

    de Fine Licht, Henrik Hjarvard; Jensen, Annette Bruun; Eilenberg, Jørgen

    .g. Entomophthora, Strongwellsea and Entomophaga). Species diversification of the obligate IPF within Entomophthoromycota thus seems to be primarily driven by co-evolutionary host adaptation to specific insect families, genera or species-complexes, but the underlying genetic factors of host adaptation...... in this fungal order are largely unknown and leave many unanswered questions. For example are the number of virulence factors increasing, or decreasing when fungal pathogens adapt to a narrow range of potential hosts? And, are host specialization based on many genetic changes with small effect or few with large...... differences and similarities in order to detect patterns of host-specific molecular adaptation....

  9. Love Thieves: Japanese Hosts and Western Convention Culture

    DEFF Research Database (Denmark)

    Westberg, Lysa Hannah Pernille Nielsen

    Japanese host culture may seem foreign to a Westerner, just like the practice of buying (male) company for pure entertainment and emotional support. Japanese women (and men) pay for the pleasure of a host's company. Hosts usually do not provide sexual favours but emotional ones, and popular hosts...... conventions. There is clearly nothing wrong with running a business which sell host services, nor is there anything wrong with mediating the contact between fans and actors, producers and writers. However, there are more than a few similarities between the two cultures, and within each culture are a few...

  10. Host social behavior and parasitic infection: A multifactorial approach

    Science.gov (United States)

    Ezenwa, V.O.

    2004-01-01

    I examined associations between several components of host social organization, including group size and gregariousness, group stability, territoriality and social class, and gastrointestinal parasite load in African bovids. At an intraspecific level, group size was positively correlated with parasite prevalence, but only when the parasite was relatively host specific and only among host species living in stable groups. Social class was also an important predictor of infection rates. Among gazelles, territorial males had higher parasite intensities than did either bachelor males or females and juveniles, suggesting that highly territorial individuals may be either more exposed or more susceptible to parasites. Associations among territoriality, grouping, and parasitism were also found across taxa. Territorial host genera were more likely to be infected with strongyle nematodes than were nonterritorial hosts, and gregarious hosts were more infected than were solitary hosts. Analyses also revealed that gregariousness and territoriality had an interactive effect on individual parasite richness, whereby hosts with both traits harbored significantly more parasite groups than did hosts with only one or neither trait. Overall, study results indicate that multiple features of host social behavior influence infection risk and suggest that synergism between traits also has important effects on host parasite load.

  11. An HST study of three very faint GRB host galaxies

    DEFF Research Database (Denmark)

    Jaunsen, A.O.; Andersen, M.I.; Hjorth, J.

    2003-01-01

    . (2002). We obtain a revised and much higher probability that the galaxies identified as hosts indeed are related to the GRBs (P(n(chance))=0.69, following Bloom et al. 2002), thereby strengthening the conclusion that GRBs are preferentially located in star-forming regions in their hosts. Apart from......As part of the HST/STIS GRB host survey program we present the detection of three faint gamma-ray burst (GRB) host galaxies based on an accurate localisation using ground-based data of the optical afterglows (OAs). A common property of these three hosts is their extreme faintness. The location...... at which GRBs occur with respect to their host galaxies and surrounding environments are robust indicators of the nature of GRB progenitors. The bursts studied here are among the four most extreme outliers, in terms of relative distance from the host center, in the recent comprehensive study of Bloom et al...

  12. Proteomic Characterization of Host Response to Yersinia pestis

    Energy Technology Data Exchange (ETDEWEB)

    Chromy, B; Perkins, J; Heidbrink, J; Gonzales, A; Murhpy, G; Fitch, J P; McCutchen-Maloney, S

    2004-05-11

    Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Y. pseudotuberculosis and Y. enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct for the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague.

  13. Host-Plant Specialization Mediates the Influence of Plant Abundance on Host Use by Flower Head-Feeding Insects.

    Science.gov (United States)

    Nobre, Paola A F; Bergamini, Leonardo L; Lewinsohn, Thomas M; Jorge, Leonardo R; Almeida-Neto, Mário

    2016-02-01

    Among-population variation in host use is a common phenomenon in herbivorous insects. The simplest and most trivial explanation for such variation in host use is the among-site variation in plant species composition. Another aspect that can influence spatial variation in host use is the relative abundance of each host-plant species compared to all available hosts. Here, we used endophagous insects that develop in flower heads of Asteraceae species as a study system to investigate how plant abundance influences the pattern of host-plant use by herbivorous insects with distinct levels of host-range specialization. Only herbivores recorded on three or more host species were included in this study. In particular, we tested two related hypotheses: 1) plant abundance has a positive effect on the host-plant preference of herbivorous insects, and 2) the relative importance of plant abundance to host-plant preference is greater for herbivorous species that use a wider range of host-plant species. We analyzed 11 herbivore species in 20 remnants of Cerrado in Southeastern Brazil. For 8 out of 11 herbivore species, plant abundance had a positive influence on host use. In contrast to our expectation, both the most specialized and the most generalist herbivores showed a stronger positive effect of plant species abundance in host use. Thus, we found evidence that although the abundance of plant species is a major factor determining the preferential use of host plants, its relative importance is mediated by the host-range specialization of herbivores.

  14. Volatile chemical cues guide host location and host selection by parasitic plants

    Science.gov (United States)

    Justin B. Runyon; Mark C. Mescher; Consuelo M. De Moraes

    2006-01-01

    The importance of plant volatiles in mediating interactions between plant species is much debated. Here, we demonstrate that the parasitic plant Cuscuta pentagona (dodder) uses volatile cues for host location. Cuscuta pentagona seedlings exhibit directed growth toward nearby tomato plants (Lycopersicon esculentum...

  15. Infection dynamics at within-host and between-host scales

    NARCIS (Netherlands)

    Severins, M.|info:eu-repo/dai/nl/304837105

    2012-01-01

    Developing and predicting the effect of control measures on the infection dynamics in parasite-host systems with many feedback loops between the different infection processes poses a challenge. Part of this challenge comes from the large heterogeneity often observed in these systems. The goal of

  16. The gut microbiota and host innate immunity: Regulators of host metabolism and metablic diseases in poultry?

    Science.gov (United States)

    The gut microbiota represents the multitudes of microbes residing in the intestine and is integral in multiple physiological processes of the host. The endogenous intestinal microflora together with other environmental factors, such as diet, play a central role in immune homeostasis. Moreover, the...

  17. Host-exclusivity and host-recurrence by wood decay fungi (Basidiomycota - Agaricomycetes in Brazilian mangroves

    Directory of Open Access Journals (Sweden)

    Georgea S. Nogueira-Melo

    2017-09-01

    Full Text Available ABSTRACT This study aimed to investigate for the first time the ecological interactions between species of Agaricomycetes and their host plants in Brazilian mangroves. Thirty-two field trips were undertaken to four mangroves in the state of Pernambuco, Brazil, from April 2009 to March 2010. One 250 x 40 m stand was delimited in each mangrove and six categories of substrates were artificially established: living Avicennia schauerian