Radioimmunoassay of measles virus hemagglutinin protein G

International Nuclear Information System (INIS)

Lund, G.A.; Salmi, A.A.

1982-01-01

Guinea pig and rabbit antisera from animals immunized with purified measles virus hemagglutinin (G) protein were used to establish a solid-phase four-layer radioimmunoassay for quantitative measurement of the G protein. The sensitivity of the assay was 2 ng of purified G protein, and 200 μg of protein from uninfected Vero cells neither decreased the sensitivity nor reacted non-specifically in the assay. Radioimmunoassay standard dose-response curves were established and unknown values interpolated from these using the logit program of a desktop computer. Using this procedure, a measles virus growth curve in infected Vero cells was determined by measurement of G protein production. Under these same conditions, hemagglutination was not sensitive enough to detect early hemagglutinin production. Viral antigens in canine distemper virus, Newcastle disease virus, parainfluenza viruses 1-4, simian virus 5, and respiratory syncytial virus-infected cell lysates did not cross-react in the radioimmunoassay. A small degree of cross-reactivity was detected with mumps viral antigens, both with Vero cell-derived (wild-type strain) and egg-derived (Enders strain) purified virus preparations and with a cell lysate antigen prepared from wild-type mumps virus-infected Vero cells. (Auth.)

Radioimmunoassay of measles virus hemagglutinin protein G

Energy Technology Data Exchange (ETDEWEB)

Lund, G A; Salmi, A A [Turku Univ. (Finland)

1982-08-01

Guinea pig and rabbit antisera from animals immunized with purified measles virus hemagglutinin (G) protein were used to establish a solid-phase four-layer radioimmunoassay for quantitative measurement of the G protein. The sensitivity of the assay was 2 ng of purified G protein, and 200 ..mu..g of protein from uninfected Vero cells neither decreased the sensitivity nor reacted non-specifically in the assay. Radioimmunoassay standard dose-response curves were established and unknown values interpolated from these using the logit program of a desktop computer. Using this procedure, a measles virus growth curve in infected Vero cells was determined by measurement of G protein production. Under these same conditions, hemagglutination was not sensitive enough to detect early hemagglutinin production. Viral antigens in canine distemper virus, Newcastle disease virus, parainfluenza viruses 1-4, simian virus 5, and respiratory syncytial virus-infected cell lysates did not cross-react in the radioimmunoassay. A small degree of cross-reactivity was detected with mumps viral antigens, both with Vero cell-derived (wild-type strain) and egg-derived (Enders strain) purified virus preparations and with a cell lysate antigen prepared from wild-type mumps virus-infected Vero cells.

Targeting Host Factors to Treat West Nile and Dengue Viral Infections

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Manoj N. Krishnan

2014-02-01

Full Text Available West Nile (WNV and Dengue (DENV viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

Factors affecting host range in a generalist seed pathogen of semi-arid shrublands

Science.gov (United States)

Julie Beckstead; Susan E. Meyer; Kurt O. Reinhart; Kellene M. Bergen; Sandra R. Holden; Heather F. Boekweg

2014-01-01

Generalist pathogens can exhibit differential success on different hosts, resulting in complex host range patterns. Several factors operate to reduce realized host range relative to potential host range, particularly under field conditions. We explored factors influencing host range of the naturally occurring generalist ascomycete grass seed pathogen Pyrenophora...

The Poxvirus C7L Host Range Factor Superfamily

OpenAIRE

Liu, Jia; Rothenburg, Stefan; McFadden, Grant

2012-01-01

Host range factors, expressed by the poxvirus family, determine the host tropism of species, tissue, and cell specificity. C7L family members exist in the genomes of most sequenced mammalian poxviruses, suggesting an evolutionarily conserved effort adapting to the hosts. In general, C7L orthologs influence the host tropism in mammalian cell culture, and for some poxviruses it is essential for the complete viral life cycle in vitro and in vivo. The C7L family members lack obvious sequence homo...

Evolutionary trends of A(H1N1 influenza virus hemagglutinin since 1918.

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Jun Shen

2009-11-01

Full Text Available The Pandemic (H1N1 2009 is spreading to numerous countries and causing many human deaths. Although the symptoms in humans are mild at present, fears are that further mutations in the virus could lead to a potentially more dangerous outbreak in subsequent months. As the primary immunity-eliciting antigen, hemagglutinin (HA is the major agent for host-driven antigenic drift in A(H3N2 virus. However, whether and how the evolution of HA is influenced by existing immunity is poorly understood for A(H1N1. Here, by analyzing hundreds of A(H1N1 HA sequences since 1918, we show the first evidence that host selections are indeed present in A(H1N1 HAs. Among a subgroup of human A(H1N1 HAs between 1918 approximately 2008, we found strong diversifying (positive selection at HA(1 156 and 190. We also analyzed the evolutionary trends at HA(1 190 and 225 that are critical determinants for receptor-binding specificity of A(H1N1 HA. Different A(H1N1 viruses appeared to favor one of these two sites in host-driven antigenic drift: epidemic A(H1N1 HAs favor HA(1 190 while the 1918 pandemic and swine HAs favor HA(1 225. Thus, our results highlight the urgency to understand the interplay between antigenic drift and receptor binding in HA evolution, and provide molecular signatures for monitoring future antigenically drifted 2009 pandemic and seasonal A(H1N1 influenza viruses.

Hemagglutinin 222D/G polymorphism facilitates fast intra-host evolution of pandemic (H1N1 2009 influenza A viruses.

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Nora Seidel

Full Text Available The amino acid substitution of aspartic acid to glycine in hemagglutinin (HA in position 222 (HA-D222G as well as HA-222D/G polymorphism of pandemic (H1N1 2009 influenza viruses (A(H1N1pdm09 were frequently reported in severe influenza in humans and mice. Their impact on viral pathogenicity and the course of influenza has been discussed controversially and the underlying mechanism remained unclarified. In the present study, BALB/c mice, infected with the once mouse lung- and cell-passaged A(H1N1pdm09 isolate A/Jena/5258/09 (mpJena/5258, developed severe pneumonia. From day 2 to 3 or 4 post infection (p.i. symptoms (body weight loss and clinical score continuously worsened. After a short disease stagnation or even recovery phase in most mice, severity of disease further increased on days 6 and 7 p.i. Thereafter, surviving mice recovered. A 45 times higher virus titer maximum in the lung than in the trachea on day 2 p.i. and significantly higher tracheal virus titers compared to lung on day 6 p.i. indicated changes in the organ tropism during infection. Sequence analysis revealed an HA-222D/G polymorphism. HA-D222 and HA-G222 variants co-circulated in lung and trachea. Whereas, HA-D222 variant predominated in the lung, HA-G222 became the major variant in the trachea after day 4 p.i. This was accompanied by lower neutralizing antibody titers and broader receptor recognition including terminal sialic acid α-2,3-linked galactose, which is abundant on mouse trachea epithelial cells. Plaque-purified HA-G222-mpJena/5258 virus induced severe influenza with maximum symptom on day 6 p.i. These results demonstrated for the first time that HA-222D/G quasispecies of A(H1N1pdm09 caused severe biphasic influenza because of fast viral intra-host evolution, which enabled partial antibody escape and minor changes in receptor binding.

A novel hemagglutinin with antiproliferative activity against tumor cells from the hallucinogenic mushroom Boletus speciosus.

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Sun, Jian; Ng, Tzi-Bun; Wang, Hexiang; Zhang, Guoqing

2014-01-01

Little was known about bioactive compounds from the hallucinogenic mushroom Boletus speciosus. In the present study, a hemagglutinin (BSH, B. speciosus hemagglutinin) was isolated from its fruiting bodies and enzymatic properties were also tested. The chromatographic procedure utilized comprised anion exchange chromatography on Q-Sepharose, cation exchange chromatography on CM-Cellulose, cation exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75. The hemagglutinin was a homodimer which was estimated to be approximately 31 kDa in size. The activity of BSH was stable up to 60°C, while there was a precipitous drop in activity when the temperature was elevated to 70°C. BSH retained 25% hemagglutinating activity when exposed to 100 mM NaOH and 25 mM HCl. The activity was potently inhibited by 1.25 mM Hg(2+) and slightly inhibited by Fe(2+), Ca(2+), and Pb(2+). None of the sugars tested showed inhibition towards BSH. Its hemagglutinating activity towards human erythrocytes type A, type B, and type AB was higher than type O. The hemagglutinin showed antiproliferative activity towards hepatoma Hep G2 cells and mouse lymphocytic leukemia cells (L1210) in vitro, with IC50 of 4.7 μ M and 7.0 μ M, respectively. It also exhibited HIV-1 reverse transcriptase inhibitory activity with an IC50 of 7.1 μ M.

Rapid Diagnostic Assay for Intact Influenza Virus Using a High Affinity Hemagglutinin Binding Protein.

Science.gov (United States)

Anderson, Caitlin E; Holstein, Carly A; Strauch, Eva-Maria; Bennett, Steven; Chevalier, Aaron; Nelson, Jorgen; Fu, Elain; Baker, David; Yager, Paul

2017-06-20

Influenza is a ubiquitous and recurring infection that results in approximately 500 000 deaths globally each year. Commercially available rapid diagnostic tests are based upon detection of the influenza nucleoprotein, which are limited in that they are unable to differentiate by species and require an additional viral lysis step. Sample preprocessing can be minimized or eliminated by targeting the intact influenza virus, thereby reducing assay complexity and leveraging the large number of hemagglutinin proteins on the surface of each virus. Here, we report the development of a paper-based influenza assay that targets the hemagglutinin protein; the assay employs a combination of antibodies and novel computationally designed, recombinant affinity proteins as the capture and detection agents. This system leverages the customizability of recombinant protein design to target the conserved receptor-binding pocket of the hemagglutinin protein and to match the trimeric nature of hemagglutinin for improved avidity. Using this assay, we demonstrate the first instance of intact influenza virus detection using a combination of antibody and affinity proteins within a porous network. The recombinant head region binder based assays yield superior analytical sensitivity as compared to the antibody based assay, with lower limits of detection of 3.54 × 10 7 and 1.34 × 10 7 CEID 50 /mL for the mixed and all binder stacks, respectively. Not only does this work describe the development of a novel influenza assay, it also demonstrates the power of recombinant affinity proteins for use in rapid diagnostic assays.

Requirement for Vibrio cholerae Integration Host Factor in Conjugative DNA Transfer

OpenAIRE

McLeod, Sarah M.; Burrus, Vincent; Waldor, Matthew K.

2006-01-01

The requirement for host factors in the transmission of integrative and conjugative elements (ICEs) has not been extensively explored. Here we tested whether integration host factor (IHF) or Fis, two host-encoded nucleoid proteins, are required for transfer of SXT, a Vibrio cholerae-derived ICE that can be transmitted to many gram-negative species. Fis did not influence the transfer of SXT to or from V. cholerae. In contrast, IHF proved to be required for V. cholerae to act as an SXT donor. I...

Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins

OpenAIRE

Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan

2015-01-01

Productive viral replication requires overcoming many barriers posed by the host innate immune system. Human sterile alpha motif domain-containing 9 (SAMD9) is a newly identified antiviral factor that is specifically targeted by poxvirus proteins belonging to the C7 family of host-range factors. Here we provide the first, to our knowledge, atomic view of two functionally divergent proteins from the C7 family and determine the molecular basis that dictates whether they can target SAMD9 effecti...

A Novel Hemagglutinin with Antiproliferative Activity against Tumor Cells from the Hallucinogenic Mushroom Boletus speciosus

Directory of Open Access Journals (Sweden)

Jian Sun

2014-01-01

Full Text Available Little was known about bioactive compounds from the hallucinogenic mushroom Boletus speciosus. In the present study, a hemagglutinin (BSH, B. speciosus hemagglutinin was isolated from its fruiting bodies and enzymatic properties were also tested. The chromatographic procedure utilized comprised anion exchange chromatography on Q-Sepharose, cation exchange chromatography on CM-Cellulose, cation exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75. The hemagglutinin was a homodimer which was estimated to be approximately 31 kDa in size. The activity of BSH was stable up to 60°C, while there was a precipitous drop in activity when the temperature was elevated to 70°C. BSH retained 25% hemagglutinating activity when exposed to 100 mM NaOH and 25 mM HCl. The activity was potently inhibited by 1.25 mM Hg2+ and slightly inhibited by Fe2+, Ca2+, and Pb2+. None of the sugars tested showed inhibition towards BSH. Its hemagglutinating activity towards human erythrocytes type A, type B, and type AB was higher than type O. The hemagglutinin showed antiproliferative activity towards hepatoma Hep G2 cells and mouse lymphocytic leukemia cells (L1210 in vitro, with IC50 of 4.7 μM and 7.0 μM, respectively. It also exhibited HIV-1 reverse transcriptase inhibitory activity with an IC50 of 7.1 μM.

Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin.

Science.gov (United States)

Doud, Michael B; Bloom, Jesse D

2016-06-03

Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin-including the stalk epitopes targeted by broadly neutralizing antibodies-have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.

Structural Characterization of the Hemagglutinin Receptor Specificity from the 2009 H1N1 Influenza Pandemic

Energy Technology Data Exchange (ETDEWEB)

Xu, Rui; McBride, Ryan; Nycholat, Corwin M.; Paulson, James C.; Wilson, Ian A. (Scripps)

2012-02-13

Influenza virus hemagglutinin (HA) is the viral envelope protein that mediates viral attachment to host cells and elicits membrane fusion. The HA receptor-binding specificity is a key determinant for the host range and transmissibility of influenza viruses. In human pandemics of the 20th century, the HA normally has acquired specificity for human-like receptors before widespread infection. Crystal structures of the H1 HA from the 2009 human pandemic (A/California/04/2009 [CA04]) in complex with human and avian receptor analogs reveal conserved recognition of the terminal sialic acid of the glycan ligands. However, favorable interactions beyond the sialic acid are found only for {alpha}2-6-linked glycans and are mediated by Asp190 and Asp225, which hydrogen bond with Gal-2 and GlcNAc-3. For {alpha}2-3-linked glycan receptors, no specific interactions beyond the terminal sialic acid are observed. Our structural and glycan microarray analyses, in the context of other high-resolution HA structures with {alpha}2-6- and {alpha}2-3-linked glycans, now elucidate the structural basis of receptor-binding specificity for H1 HAs in human and avian viruses and provide a structural explanation for the preference for {alpha}2-6 siaylated glycan receptors for the 2009 pandemic swine flu virus.

Host and Viral Factors in HIV-Mediated Bystander Apoptosis

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Garg, Himanshu; Joshi, Anjali

2017-01-01

Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402

Hemagglutinin Typing as an Aid in Identification of Biochemically Atypical Escherichia coli Strains

OpenAIRE

Crichton, Pamela B.; Ip, S. M.; Old, D. C.

1981-01-01

Tests for the presence of mannose-sensitive and mannose-resistant, eluting hemagglutinins and fimbriae were helpful in indicating whether biochemically atypical strains of the tribe Escherichieae might be escherichiae or shigellae.

Unique Infectious Strategy of H5N1 Avian Influenza Virus Is Governed by the Acid-Destabilized Property of Hemagglutinin.

Science.gov (United States)

Daidoji, Tomo; Watanabe, Yohei; Arai, Yasuha; Kajikawa, Junichi; Hirose, Ryohei; Nakaya, Takaaki

Highly pathogenic avian influenza (HPAI) H5N1 virus emerged in 1997 as a zoonotic disease in Hong Kong. It has since spread to Asia and Europe and is a serious threat to both the poultry industry and human health. For effective surveillance and possible prevention/control of HPAI H5N1 viruses, it is necessary to understand the molecular mechanism underlying HPAI H5N1 pathogenesis. The hemagglutinin (HA) protein of influenza A viruses (IAVs) is one of the major determinants of host adaptation, transmissibility, and viral virulence. The main function of the HA protein is to facilitate viral entry and viral genome release within host cells before infection. To achieve viral infection, IAVs belonging to different subtypes or strains induce viral-cell membrane fusion at different endosomal pH levels after internalization through endocytosis. However, host-specific endosomal pH also affects induction of membrane fusion followed by infection. The HA protein of HPAI H5N1 has a higher pH threshold for membrane fusion than the HA protein of classical avian influenza viruses. Although this particular property of HA (which governs viral infection) is prone to deactivation in the avian intestine or in an ambient environment, it facilitates efficient infection of host cells, resulting in a broad host tropism, regardless of the pH in the host endosome. Accumulated knowledge, together with further research, about the HA-governed mechanism underlying HPAI H5N1 virulence (i.e., receptor tropism and pH-dependent viral-cell membrane fusion) will be helpful for developing effective surveillance strategies and for prevention/control of HPAI H5N1 infection.

Hemagglutinin Typing as an Aid in Identification of Biochemically Atypical Escherichia coli Strains

Science.gov (United States)

Crichton, Pamela B.; Ip, S. M.; Old, D. C.

1981-01-01

Tests for the presence of mannose-sensitive and mannose-resistant, eluting hemagglutinins and fimbriae were helpful in indicating whether biochemically atypical strains of the tribe Escherichieae might be escherichiae or shigellae. PMID:7334072

Foreign Direct Investment, Host Country Factors and Economic Growth

OpenAIRE

Edna Maeyen Solomon

2011-01-01

This paper analyses how the levels of economic development, human capital, financial development and the qualities of the economic and political environments in host countries simultaneously affects the impact of aggregate inflows of Foreign Direct Investment (FDI) on economic growth. Multiple interaction terms are employed between inward FDI and each of the host country factors mentioned above. The System GMM estimator is applied to a panel of 111 countries from 1981 to 2005. The results sho...

Gold nanoparticles conjugating recombinant influenza hemagglutinin trimers and flagellin enhanced mucosal cellular immunity.

Science.gov (United States)

Wang, Chao; Zhu, Wandi; Luo, Yuan; Wang, Bao-Zhong

2018-04-09

The immunogenicity of subunit vaccines can be augmented by formulating them into nanoparticles. We conjugated recombinant trimetric influenza A/Aichi/2/68(H3N2) hemagglutinin (HA) onto functionalized gold nanoparticles (AuNPs) surfaces in a repetitive, oriented configuration. To further improve the immunogenicity, we generated Toll-like receptor 5 (TLR5) agonist flagellin (FliC)-coupled AuNPs as particulate adjuvants. Intranasal immunizations with an AuNP-HA and AuNP-FliC particle mixture elicited strong mucosal and systemic immune responses that protected hosts against lethal influenza challenges. Compared with the AuNP-HA alone group, the addition of AuNP-FliC improved mucosal B cell responses as characterized by elevated influenza specific IgA and IgG levels in nasal, tracheal, and lung washes. AuNP-HA/AuNP-FliC also stimulated antigen-specific interferon-γ (IFN-γ)-secreting CD4 + cell proliferation and induced strong effector CD8 + T cell activation. Our results indicate that intranasal co-delivery of antigen and adjuvant-displaying AuNPs enhanced vaccine efficacy by inducing potent cellular immune responses. Copyright © 2018. Published by Elsevier Inc.

Structure and receptor binding preferences of recombinant hemagglutinins from avian and human H6 and H10 influenza A virus subtypes.

Science.gov (United States)

Yang, Hua; Carney, Paul J; Chang, Jessie C; Villanueva, Julie M; Stevens, James

2015-04-01

During 2013, three new avian influenza A virus subtypes, A(H7N9), A(H6N1), and A(H10N8), resulted in human infections. While the A(H7N9) virus resulted in a significant epidemic in China across 19 provinces and municipalities, both A(H6N1) and A(H10N8) viruses resulted in only a few human infections. This study focuses on the major surface glycoprotein hemagglutinins from both of these novel human viruses. The detailed structural and glycan microarray analyses presented here highlight the idea that both A(H6N1) and A(H10N8) virus hemagglutinins retain a strong avian receptor binding preference and thus currently pose a low risk for sustained human infections. Human infections with zoonotic influenza virus subtypes continue to be a great public health concern. We report detailed structural analysis and glycan microarray data for recombinant hemagglutinins from A(H6N1) and A(H10N8) viruses, isolated from human infections in 2013, and compare them with hemagglutinins of avian origin. This is the first structural report of an H6 hemagglutinin, and our results should further the understanding of these viruses and provide useful information to aid in the continuous surveillance of these zoonotic influenza viruses. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Roles of Hemagglutinin Phe-95 in Receptor Binding and Pathogenicity of Influenza B Virus

Science.gov (United States)

Ni, Fengyun; Mbawuike, Innocent Nnadi; Kondrashkina, Elena; Wang, Qinghua

2014-01-01

Diverged ~4,000 years ago, influenza B virus has several important differences from influenza A virus, including lower receptor-binding affinity and highly restricted host range. Based on our prior structural studies, we hypothesized that a single-residue difference in the receptor-binding site of hemagglutinin (HA), Phe-95 in influenza B virus versus Tyr-98 in influenza A/H1~H15, is possibly a key determinant for the low receptor-binding affinity. Here we demonstrate that the mutation Phe95→Tyr in influenza B virus HA restores all three hydrogen bonds made by Tyr-98 in influenza A/H3 HA and has the potential to enhance receptor binding. However, the full realization of this potential is influenced by the local environment into which the mutation is introduced. The binding and replication of the recombinant viruses correlate well with the receptor-binding capabilities of HA. These results are discussed in relation to the roles of Phe-95 in receptor binding and pathogenicity of influenza B virus. PMID:24503069

Borrelia host adaptation Regulator (BadR) regulates rpoS to modulate host adaptation and virulence factors in Borrelia burgdorferi

OpenAIRE

Miller, Christine L.; Rajasekhar Karna, S. L.; Seshu, J.

2013-01-01

The RpoS transcription factor of Borrelia burgdorferi is a “gatekeeper” because it activates genes required for spirochetes to transition from tick to vertebrate hosts. However, it remains unknown how RpoS becomes repressed to allow the spirochetes to transition back from the vertebrate host to the tick vector. Here we show that a putative carbohydrate-responsive regulatory protein, designated BadR (Borrelia host adaptation Regulator), is a transcriptional repressor of rpoS. BadR levels are e...

Host Factors in Ebola Infection.

Science.gov (United States)

Rasmussen, Angela L

2016-08-31

Ebola virus (EBOV) emerged in West Africa in 2014 to devastating effect, and demonstrated that infection can cause a broad range of severe disease manifestations. As the virus itself was genetically similar to other Zaire ebolaviruses, the spectrum of pathology likely resulted from variable responses to infection in a large and genetically diverse population. This review comprehensively summarizes current knowledge of the host response to EBOV infection, including pathways hijacked by the virus to facilitate replication, host processes that contribute directly to pathogenesis, and host-pathogen interactions involved in subverting or antagonizing host antiviral immunity.

Host and Environmental Factors Affecting the Intestinal Microbiota in Chickens.

Science.gov (United States)

Kers, Jannigje G; Velkers, Francisca C; Fischer, Egil A J; Hermes, Gerben D A; Stegeman, J A; Smidt, Hauke

2018-01-01

The initial development of intestinal microbiota in poultry plays an important role in production performance, overall health and resistance against microbial infections. Multiplexed sequencing of 16S ribosomal RNA gene amplicons is often used in studies, such as feed intervention or antimicrobial drug trials, to determine corresponding effects on the composition of intestinal microbiota. However, considerable variation of intestinal microbiota composition has been observed both within and across studies. Such variation may in part be attributed to technical factors, such as sampling procedures, sample storage, DNA extraction, the choice of PCR primers and corresponding region to be sequenced, and the sequencing platforms used. Furthermore, part of this variation in microbiota composition may also be explained by different host characteristics and environmental factors. To facilitate the improvement of design, reproducibility and interpretation of poultry microbiota studies, we have reviewed the literature on confounding factors influencing the observed intestinal microbiota in chickens. First, it has been identified that host-related factors, such as age, sex, and breed, have a large effect on intestinal microbiota. The diversity of chicken intestinal microbiota tends to increase most during the first weeks of life, and corresponding colonization patterns seem to differ between layer- and meat-type chickens. Second, it has been found that environmental factors, such as biosecurity level, housing, litter, feed access and climate also have an effect on the composition of the intestinal microbiota. As microbiota studies have to deal with many of these unknown or hidden host and environmental variables, the choice of study designs can have a great impact on study outcomes and interpretation of the data. Providing details on a broad range of host and environmental factors in articles and sequence data repositories is highly recommended. This creates opportunities to

Host and Environmental Factors Affecting the Intestinal Microbiota in Chickens

Directory of Open Access Journals (Sweden)

Jannigje G. Kers

2018-02-01

Full Text Available The initial development of intestinal microbiota in poultry plays an important role in production performance, overall health and resistance against microbial infections. Multiplexed sequencing of 16S ribosomal RNA gene amplicons is often used in studies, such as feed intervention or antimicrobial drug trials, to determine corresponding effects on the composition of intestinal microbiota. However, considerable variation of intestinal microbiota composition has been observed both within and across studies. Such variation may in part be attributed to technical factors, such as sampling procedures, sample storage, DNA extraction, the choice of PCR primers and corresponding region to be sequenced, and the sequencing platforms used. Furthermore, part of this variation in microbiota composition may also be explained by different host characteristics and environmental factors. To facilitate the improvement of design, reproducibility and interpretation of poultry microbiota studies, we have reviewed the literature on confounding factors influencing the observed intestinal microbiota in chickens. First, it has been identified that host-related factors, such as age, sex, and breed, have a large effect on intestinal microbiota. The diversity of chicken intestinal microbiota tends to increase most during the first weeks of life, and corresponding colonization patterns seem to differ between layer- and meat-type chickens. Second, it has been found that environmental factors, such as biosecurity level, housing, litter, feed access and climate also have an effect on the composition of the intestinal microbiota. As microbiota studies have to deal with many of these unknown or hidden host and environmental variables, the choice of study designs can have a great impact on study outcomes and interpretation of the data. Providing details on a broad range of host and environmental factors in articles and sequence data repositories is highly recommended. This creates

Purification and production of monospecific antibody to the hemagglutinin from Subtype H5N1 influenza virus

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Simson Tarigan

2010-12-01

Full Text Available The purpose of this study was to purify the hemagglutinin from H5N1 virus and to generate monospecific antibody appropriate for production of sensitive and specific immunoassay for H5N1 avian influenza. For this purpose, a local isolate H5N1 virus (A/Ck/West Java/Hamd/2006 was propagated in chicken embryos. The viral pellet was dissolved in a Triton-X-100 solution, undissolved viral particles were pelleted by ultracentrifuge, and the supernatant containing viral surface glycoproteins (Hemagglutinin and neuraminidase was collected. The neuraminidase in the supernatant was absorbed by passing the supernatant through an Oxamic-acid-superose column. After dialyzing extensively, the filtrate was further fractionated with an anion exchange chromatography (Q-sepharose column. Proteins adsorbed by the column were eluted stepwisely with 0.10, 0.25, 0.25 and 0.75 M NaCl in 20 mM Tris, ph 8. Hemagglutinin (H5 was found to be eluted from the column with the 0.5 M NaCl elution buffer. The purified H5 was free from other viral proteins based on immunoassays using commercial antibodies to H5N1 nucleoprotein and neuraminidase. When used as ELISA’s coating antigen, the purified H5 proved to be sensitive and specific for hemagglutinin H5. Cross reactions with other type-A-influenza virus, H6, H7 dan H9, were negligibly low. For the production of monospecific antiserum, the purified H5 was separated with SDS-PAGE, the band containing the H5 monomer was cut out , homogenised and injected into rabbits. The antiserum was capable of detecting the presence of inactivated H5N1 virus in a very dilute suspension, with a detection limit of 0.04 heagglutination (HA unit. The purified hemagglutinin and the serum raised against it should be useful for developing specific, sensitive and affordable immunoassay for H5N1 avian influenza.

Requirement for Vibrio cholerae integration host factor in conjugative DNA transfer.

Science.gov (United States)

McLeod, Sarah M; Burrus, Vincent; Waldor, Matthew K

2006-08-01

The requirement for host factors in the transmission of integrative and conjugative elements (ICEs) has not been extensively explored. Here we tested whether integration host factor (IHF) or Fis, two host-encoded nucleoid proteins, are required for transfer of SXT, a Vibrio cholerae-derived ICE that can be transmitted to many gram-negative species. Fis did not influence the transfer of SXT to or from V. cholerae. In contrast, IHF proved to be required for V. cholerae to act as an SXT donor. In the absence of IHF, V. cholerae displayed a modest defect for serving as an SXT recipient. Surprisingly, SXT integration into or excision from the V. cholerae chromosome, which requires an SXT-encoded integrase related to lambda integrase, did not require IHF. Therefore, the defect in SXT transmission in the V. cholerae IHF mutant is probably not related to IHF's ability to promote DNA recombination. The V. cholerae IHF mutant was also highly impaired as a donor of RP4, a broad-host-range conjugative plasmid. Thus, the V. cholerae IHF mutant appears to have a general defect in conjugation. Escherichia coli IHF mutants were not impaired as donors or recipients of SXT or RP4, indicating that IHF is a V. cholerae-specific conjugation factor.

Computational design of protein interactions: designing proteins that neutralize influenza by inhibiting its hemagglutinin surface protein

Science.gov (United States)

Fleishman, Sarel

2012-02-01

Molecular recognition underlies all life processes. Design of interactions not seen in nature is a test of our understanding of molecular recognition and could unlock the vast potential of subtle control over molecular interaction networks, allowing the design of novel diagnostics and therapeutics for basic and applied research. We developed the first general method for designing protein interactions. The method starts by computing a region of high affinity interactions between dismembered amino acid residues and the target surface and then identifying proteins that can harbor these residues. Designs are tested experimentally for binding the target surface and successful ones are affinity matured using yeast cell surface display. Applied to the conserved stem region of influenza hemagglutinin we designed two unrelated proteins that, following affinity maturation, bound hemagglutinin at subnanomolar dissociation constants. Co-crystal structures of hemagglutinin bound to the two designed binders were within 1Angstrom RMSd of their models, validating the accuracy of the design strategy. One of the designed proteins inhibits the conformational changes that underlie hemagglutinin's cell-invasion functions and blocks virus infectivity in cell culture, suggesting that such proteins may in future serve as diagnostics and antivirals against a wide range of pathogenic influenza strains. We have used this method to obtain experimentally validated binders of several other target proteins, demonstrating the generality of the approach. We discuss the combination of modeling and high-throughput characterization of design variants which has been key to the success of this approach, as well as how we have used the data obtained in this project to enhance our understanding of molecular recognition. References: Science 332:816 JMB, in press Protein Sci 20:753

Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

Energy Technology Data Exchange (ETDEWEB)

Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R., E-mail: grw7@cornell.edu

2014-07-25

Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.

Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

International Nuclear Information System (INIS)

Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R.

2014-01-01

Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza

DMPD: The interferon regulatory factor family in host defense: mechanism of action. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of acti....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism

Structure of the parainfluenza virus 5 (PIV5 hemagglutinin-neuraminidase (HN ectodomain.

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Brett D Welch

Full Text Available Paramyxoviruses cause a wide variety of human and animal diseases. They infect host cells using the coordinated action of two surface glycoproteins, the receptor binding protein (HN, H, or G and the fusion protein (F. HN binds sialic acid on host cells (hemagglutinin activity and hydrolyzes these receptors during viral egress (neuraminidase activity, NA. Additionally, receptor binding is thought to induce a conformational change in HN that subsequently triggers major refolding in homotypic F, resulting in fusion of virus and target cell membranes. HN is an oligomeric type II transmembrane protein with a short cytoplasmic domain and a large ectodomain comprising a long helical stalk and large globular head domain containing the enzymatic functions (NA domain. Extensive biochemical characterization has revealed that HN-stalk residues determine F specificity and activation. However, the F/HN interaction and the mechanisms whereby receptor binding regulates F activation are poorly defined. Recently, a structure of Newcastle disease virus (NDV HN ectodomain revealed the heads (NA domains in a "4-heads-down" conformation whereby two of the heads form a symmetrical interaction with two sides of the stalk. The interface includes stalk residues implicated in triggering F, and the heads sterically shield these residues from interaction with F (at least on two sides. Here we report the x-ray crystal structure of parainfluenza virus 5 (PIV5 HN ectodomain in a "2-heads-up/2-heads-down" conformation where two heads (covalent dimers are in the "down position," forming a similar interface as observed in the NDV HN ectodomain structure, and two heads are in an "up position." The structure supports a model in which the heads of HN transition from down to up upon receptor binding thereby releasing steric constraints and facilitating the interaction between critical HN-stalk residues and F.

Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice.

Science.gov (United States)

Matsuoka, Yumiko; Swayne, David E; Thomas, Colleen; Rameix-Welti, Marie-Anne; Naffakh, Nadia; Warnes, Christine; Altholtz, Melanie; Donis, Ruben; Subbarao, Kanta

2009-05-01

Following circulation of avian influenza H5 and H7 viruses in poultry, the hemagglutinin (HA) can acquire additional glycosylation sites, and the neuraminidase (NA) stalk becomes shorter. We investigated whether these features play a role in the pathogenesis of infection in mammalian hosts. From 1996 to 2007, H5N1 viruses with a short NA stalk have become widespread in several avian species. Compared to viruses with a long-stalk NA, viruses with a short-stalk NA showed a decreased capacity to elute from red blood cells and an increased virulence in mice, but not in chickens. The presence of additional HA glycosylation sites had less of an effect on virulence than did NA stalk length. The short-stalk NA of H5N1 viruses circulating in Asia may contribute to virulence in humans.

Neuraminidase Stalk Length and Additional Glycosylation of the Hemagglutinin Influence the Virulence of Influenza H5N1 Viruses for Mice▿

Science.gov (United States)

Matsuoka, Yumiko; Swayne, David E.; Thomas, Colleen; Rameix-Welti, Marie-Anne; Naffakh, Nadia; Warnes, Christine; Altholtz, Melanie; Donis, Ruben; Subbarao, Kanta

2009-01-01

Following circulation of avian influenza H5 and H7 viruses in poultry, the hemagglutinin (HA) can acquire additional glycosylation sites, and the neuraminidase (NA) stalk becomes shorter. We investigated whether these features play a role in the pathogenesis of infection in mammalian hosts. From 1996 to 2007, H5N1 viruses with a short NA stalk have become widespread in several avian species. Compared to viruses with a long-stalk NA, viruses with a short-stalk NA showed a decreased capacity to elute from red blood cells and an increased virulence in mice, but not in chickens. The presence of additional HA glycosylation sites had less of an effect on virulence than did NA stalk length. The short-stalk NA of H5N1 viruses circulating in Asia may contribute to virulence in humans. PMID:19225004

Unique Structural Features of Influenza Virus H15 Hemagglutinin

Energy Technology Data Exchange (ETDEWEB)

Tzarum, Netanel; McBride, Ryan; Nycholat, Corwin M.; Peng, Wenjie; Paulson, James C.; Wilson, Ian A. (Scripps)

2017-04-12

Influenza A H15 viruses are members of a subgroup (H7-H10-H15) of group 2 hemagglutinin (HA) subtypes that include H7N9 and H10N8 viruses that were isolated from humans during 2013. The isolation of avian H15 viruses is, however, quite rare and, until recently, geographically restricted to wild shorebirds and waterfowl in Australia. The HAs of H15 viruses contain an insertion in the 150-loop (loop beginning at position 150) of the receptor-binding site common to this subgroup and a unique insertion in the 260-loop compared to any other subtype. Here, we show that the H15 HA has a high preference for avian receptor analogs by glycan array analyses. The H15 HA crystal structure reveals that it is structurally closest to H7N9 HA, but the head domain of the H15 trimer is wider than all other HAs due to a tilt and opening of the HA1 subunits of the head domain. The extended 150-loop of the H15 HA retains the conserved conformation as in H7 and H10 HAs. Furthermore, the elongated 260-loop increases the exposed HA surface and can contribute to antigenic variation in H15 HAs. Since avian-origin H15 HA viruses have been shown to cause enhanced disease in mammalian models, further characterization and immune surveillance of H15 viruses are warranted.

IMPORTANCEIn the last 2 decades, an apparent increase has been reported for cases of human infection by emerging avian influenza A virus subtypes, including H7N9 and H10N8 viruses isolated during 2013. H15 is the other member of the subgroup of influenza A virus group 2 hemagglutinins (HAs) that also include H7 and H10. H15 viruses have been restricted to Australia, but recent isolation of H15 viruses in western Siberia suggests that they could be spread more globally via the avian flyways that converge and emanate from this region. Here we report on characterization of the three-dimensional structure and receptor specificity of the H15 hemagglutinin, revealing distinct features and specificities that can

Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins.

Science.gov (United States)

Meng, Xiangzhi; Krumm, Brian; Li, Yongchao; Deng, Junpeng; Xiang, Yan

2015-12-01

Human sterile alpha motif domain-containing 9 (SAMD9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus C7 protein. To understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of C7 and myxoma virus M64, a C7 family member that is unable to antagonize SAMD9. Despite their different functions and only 23% sequence identity, the two proteins have very similar overall structures, displaying a previously unidentified fold comprised of a compact 12-stranded antiparallel β-sandwich wrapped in two short α helices. Extensive structure-guided mutagenesis of C7 identified three loops clustered on one edge of the β sandwich as critical for viral replication and binding with SAMD9. The loops are characterized with functionally important negatively charged, positively charged, and hydrophobic residues, respectively, together forming a unique "three-fingered molecular claw." The key residues of the claw are not conserved in two C7 family members that do not antagonize SAMD9 but are conserved in distantly related C7 family members from four poxvirus genera that infect diverse mammalian species. Indeed, we found that all in the latter group of proteins bind SAMD9. Taken together, our data indicate that diverse mammalian poxviruses use a conserved molecular claw in a C7-like protein to target SAMD9 and overcome host restriction.

Host factors in nidovirus replication

NARCIS (Netherlands)

Wilde, Adriaan Hugo de

2013-01-01

The interplay between nidoviruses and the infected host cell was investigated. Arterivirus RNA-synthesising activity was shown to depend on intact membranes and on a cytosolic host protein which does not cosediment with the RTC. Furthermore, the immunosuppressant drug cyclosporin A (CsA) blocks

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

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Sudhir Kumar Rai

2017-12-01

Full Text Available Retroviruses and Long Terminal Repeat (LTR-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

Science.gov (United States)

Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak; Levin, Henry L

2017-12-01

Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model.

Science.gov (United States)

Ermler, Megan E; Kirkpatrick, Ericka; Sun, Weina; Hai, Rong; Amanat, Fatima; Chromikova, Veronika; Palese, Peter; Krammer, Florian

2017-06-15

Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection. IMPORTANCE While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed. Copyright © 2017 American Society for Microbiology.

Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors

Science.gov (United States)

Rahme, Laurence G.; Tan, Man-Wah; Le, Long; Wong, Sandy M.; Tompkins, Ronald G.; Calderwood, Stephen B.; Ausubel, Frederick M.

1997-01-01

We used plants as an in vivo pathogenesis model for the identification of virulence factors of the human opportunistic pathogen Pseudomonas aeruginosa. Nine of nine TnphoA mutant derivatives of P. aeruginosa strain UCBPP-PA14 that were identified in a plant leaf assay for less pathogenic mutants also exhibited significantly reduced pathogenicity in a burned mouse pathogenicity model, suggesting that P. aeruginosa utilizes common strategies to infect both hosts. Seven of these nine mutants contain TnphoA insertions in previously unknown genes. These results demonstrate that an alternative nonvertebrate host of a human bacterial pathogen can be used in an in vivo high throughput screen to identify novel bacterial virulence factors involved in mammalian pathogenesis. PMID:9371831

Immunization with plasmid DNA encoding the hemagglutinin and the nucleoprotein confers robust protection against a lethal canine distemper virus challenge.

Science.gov (United States)

Dahl, Lotte; Jensen, Trine Hammer; Gottschalck, Elisabeth; Karlskov-Mortensen, Peter; Jensen, Tove Dannemann; Nielsen, Line; Andersen, Mads Klindt; Buckland, Robin; Wild, T Fabian; Blixenkrone-Møller, Merete

2004-09-09

We have investigated the protective effect of immunization of a highly susceptible natural host of canine distemper virus (CDV) with DNA plasmids encoding the viral nucleoprotein (N) and hemagglutinin (H). The combined intradermal and intramuscular routes of immunization elicited high virus-neutralizing serum antibody titres in mink (Mustela vison). To mimic natural exposure, we also conducted challenge infection by horizontal transmission from infected contact animals. Other groups received a lethal challenge infection by administration to the mucosae of the respiratory tract and into the muscle. One of the mink vaccinated with N plasmid alone developed severe disease after challenge. In contrast, vaccination with the H plasmid together with the N plasmid conferred solid protection against disease and we were unable to detect CDV infection in PBMCs or in different tissues after challenge. Our findings show that DNA immunization by the combined intradermal and intramuscular routes can confer solid protective immunity against naturally transmitted morbillivirus infection and disease.

Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity.

Science.gov (United States)

Lai, Alex L; Park, Heather; White, Judith M; Tamm, Lukas K

2006-03-03

The fusion peptide of influenza hemagglutinin is crucial for cell entry of this virus. Previous studies showed that this peptide adopts a boomerang-shaped structure in lipid model membranes at the pH of membrane fusion. To examine the role of the boomerang in fusion, we changed several residues proposed to stabilize the kink in this structure and measured fusion. Among these, mutants E11A and W14A expressed hemagglutinins with hemifusion and no fusion activities, and F9A and N12A had no effect on fusion, respectively. Binding enthalpies and free energies of mutant peptides to model membranes and their ability to perturb lipid bilayer structures correlated well with the fusion activities of the parent full-length molecules. The structure of W14A determined by NMR and site-directed spin labeling features a flexible kink that points out of the membrane, in sharp contrast to the more ordered boomerang of the wild-type, which points into the membrane. A specific fixed angle boomerang structure is thus required to support membrane fusion.

Patterns of predicted T-cell epitopes associated with antigenic drift in influenza H3N2 hemagglutinin.

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E Jane Homan

Full Text Available Antigenic drift allowing escape from neutralizing antibodies is an important feature of transmission and survival of influenza viruses in host populations. Antigenic drift has been studied in particular detail for influenza A H3N2 and well defined antigenic clusters of this virus documented. We examine how host immunogenetics contributes to determination of the antibody spectrum, and hence the immune pressure bringing about antigenic drift. Using uTOPE™ bioinformatics analysis of predicted MHC binding, based on amino acid physical property principal components, we examined the binding affinity of all 9-mer and 15-mer peptides within the hemagglutinin 1 (HA1 of 447 H3N2 virus isolates to 35 MHC-I and 14 MHC-II alleles. We provide a comprehensive map of predicted MHC-I and MHC-II binding affinity for a broad array of HLA alleles for the H3N2 influenza HA1 protein. Each HLA allele exhibited a characteristic predicted binding pattern. Cluster analysis for each HLA allele shows that patterns based on predicted MHC binding mirror those described based on antibody binding. A single amino acid mutation or position displacement can result in a marked difference in MHC binding and hence potential T-helper function. We assessed the impact of individual amino acid changes in HA1 sequences between 10 virus isolates from 1968-2002, representative of antigenic clusters, to understand the changes in MHC binding over time. Gain and loss of predicted high affinity MHC-II binding sites with cluster transitions were documented. Predicted high affinity MHC-II binding sites were adjacent to antibody binding sites. We conclude that host MHC diversity may have a major determinant role in the antigenic drift of influenza A H3N2.

Dual function of the hemagglutinin H5 fused to chicken CD154 in a ...

African Journals Online (AJOL)

Dual function of the hemagglutinin H5 fused to chicken CD154 in a potential strategy of DIVA against avian influenza disease: preliminary study. AG Pose, ES Rodriguez, AC Mendez, JN Gomez, AV Redondo, ER Rodriguez, EMG Ramos, AA Gutierrez, MPR Molto, DG Roche, YS Ugalde, AM Lopez ...

Industrial production of clotting factors: Challenges of expression, and choice of host cells.

Science.gov (United States)

Kumar, Sampath R

2015-07-01

The development of recombinant forms of blood coagulation factors as safer alternatives to plasma derived factors marked a major advance in the treatment of common coagulation disorders. These are complex proteins, mostly enzymes or co-enzymes, involving multiple post-translational modifications, and therefore are difficult to express. This article reviews the nature of the expression challenges for the industrial production of these factors, vis-à-vis the translational and post-translational bottlenecks, as well as the choice of host cell lines for high-fidelity production. For achieving high productivities of vitamin K dependent proteins, which include factors II (prothrombin), VII, IX and X, and protein C, host cell limitation of γ-glutamyl carboxylation is a major bottleneck. Despite progress in addressing this, involvement of yet unidentified protein(s) impedes a complete cell engineering solution. Human factor VIII expresses at very low levels due to limitations at several steps in the protein secretion pathway. Protein and cell engineering, vector improvement and alternate host cells promise improvement in the productivity. Production of Von Willebrand factor is constrained by its large size, complex structure, and the need for extensive glycosylation and disulfide-bonded oligomerization. All the licensed therapeutic factors are produced in CHO, BHK or HEK293 cells. While HEK293 is a recent adoption, BHK cells appear to be disfavored. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin-neuraminidase (HN) glycoprotein.

Science.gov (United States)

Sun, Junfeng; Han, Zongxi; Qi, Tianming; Zhao, Ran; Liu, Shengwang

2017-12-08

Galectin-1 is an important immunoregulatory factor and can mediate the host-pathogen interaction via binding glycans on the surface of various viruses. We previously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs. We also found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro We confirmed that CG-1B interacted with NDV hemagglutinin-neuraminidase (HN) glycoprotein, in which the specific G4 N -glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N -glycans on HN glycoprotein. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Epitope Dampening Monotypic Measles Virus Hemagglutinin Glycoprotein Results in Resistance to Cocktail of Monoclonal Antibodies

Science.gov (United States)

Lech, Patrycja J.; Tobin, Gregory J.; Bushnell, Ruth; Gutschenritter, Emily; Pham, Linh D.; Nace, Rebecca; Verhoeyen, Els; Cosset, François-Loïc; Muller, Claude P.; Russell, Stephen J.; Nara, Peter L.

2013-01-01

The measles virus (MV) is serologically monotypic. Life-long immunity is conferred by a single attack of measles or following vaccination with the MV vaccine. This is contrary to viruses such as influenza, which readily develop resistance to the immune system and recur. A better understanding of factors that restrain MV to one serotype may allow us to predict if MV will remain monotypic in the future and influence the design of novel MV vaccines and therapeutics. MV hemagglutinin (H) glycoprotein, binds to cellular receptors and subsequently triggers the fusion (F) glycoprotein to fuse the virus into the cell. H is also the major target for neutralizing antibodies. To explore if MV remains monotypic due to a lack of plasticity of the H glycoprotein, we used the technology of Immune Dampening to generate viruses with rationally designed N-linked glycosylation sites and mutations in different epitopes and screened for viruses that escaped monoclonal antibodies (mAbs). We then combined rationally designed mutations with naturally selected mutations to generate a virus resistant to a cocktail of neutralizing mAbs targeting four different epitopes simultaneously. Two epitopes were protected by engineered N-linked glycosylations and two epitopes acquired escape mutations via two consecutive rounds of artificial selection in the presence of mAbs. Three of these epitopes were targeted by mAbs known to interfere with receptor binding. Results demonstrate that, within the epitopes analyzed, H can tolerate mutations in different residues and additional N-linked glycosylations to escape mAbs. Understanding the degree of change that H can tolerate is important as we follow its evolution in a host whose immunity is vaccine induced by genotype A strains instead of multiple genetically distinct wild-type MVs. PMID:23300970

An Immunosensor Based on Antibody Binding Fragments Attached to Gold Nanoparticles for the Detection of Peptides Derived from Avian Influenza Hemagglutinin H5

Directory of Open Access Journals (Sweden)

Urszula Jarocka

2014-08-01

Full Text Available This paper concerns the development of an immunosensor for detection of peptides derived from avian influenza hemagglutinin H5. Its preparation consists of successive gold electrode modification steps: (i modification with 1,6-hexanedithiol and gold colloidal nanoparticles; (ii immobilization of antibody-binding fragments (Fab’ of anti-hemagglutinin H5 monoclonal antibodies Mab 6-9-1 via S-Au covalent bonds; and (iii covering the remaining free space on the electrode surfaces with bovine serum albumin. The interactions between Fab’ fragments and hemagglutinin (HA variants have been explored with electrochemical impedance spectroscopy (EIS in the presence of [Fe(CN6]3−/4− as an electroactive marker. The immunosensor was able to recognize three different His-tagged variants of recombinant hemagglutinin from H5N1 viruses: H1 subunit (17–340 residues of A/swan/Poland/305-135V08/2006, the long HA (17–530 residues A/Bar-headed Goose/Qinghai/12/2005 and H1 subunit (1–345 residues of A/Vietnam/1194/2004. The strongest response has been observed for the long variant with detection limit of 2.2 pg/mL and dynamic range from 4.0 to 20.0 pg/mL.

A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

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Mohamed Lamine Hafirassou

2017-12-01

Full Text Available Dengue virus (DENV infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT and oligosaccharyltransferase (OST complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.

Host-Country Related Risk Factors in International Construction: Meta-Analysis

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Güzin AYDOGAN

2014-09-01

Full Text Available Internationalization has been on the agenda of construction firms as a strategic option in global competition. Due to globalization every sector including the construction industry has faced with high levels of competitiveness, uncertainty, and risk. International construction involves common risks to domestic construction, as well as risks that are related to the host country. These risks have serious effects on the performance of international projects. Since the sustainable competitiveness of international contractors depends largely on the effective management of these risks, their assessment becomes vital for the success of international contractors. The main aim of this study is to analyse the risks for international construction projects that are related to the host country. Meta-analysis technique is used in order to determine these risks. This paper, therefore, reviews the literature that has been published in four most respected construction and management journals, these being; Journal of Construction Engineering and Management, Journal of Management in Engineering, Construction Management and Economics, and International Journal of Project Management for the period of 2000-2010. International construction risk assessment models are also reviewed within the context of this study, since host country related risk factors were found to have serious effects on the profitability of international contractors due to literature review. As a result; political stability, law and regulations, exchange rate risk, cultural differences, inflation, expropriation, tax discrimination, language barrier, bribery and corruption, force majeure, and societal conflicts in the host country are found to be the most important risk factors in international construction. Findings of this study can be used in risk assessment models for international construction projects.

DMPD: Macrophage migration inhibitory factor and host innate immune responses tomicrobes. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 14620137 Macrophage migration inhibitory factor and host innate immune responses to...microbes. Calandra T. Scand J Infect Dis. 2003;35(9):573-6. (.png) (.svg) (.html) (.csml) Show Macrophage migration... inhibitory factor and host innate immune responses tomicrobes. PubmedID 14620137 Title Macrophage migration

Host-derived, pore-forming toxin-like protein and trefoil factor complex protects the host against microbial infection.

Science.gov (United States)

Xiang, Yang; Yan, Chao; Guo, Xiaolong; Zhou, Kaifeng; Li, Sheng'an; Gao, Qian; Wang, Xuan; Zhao, Feng; Liu, Jie; Lee, Wen-Hui; Zhang, Yun

2014-05-06

Aerolysins are virulence factors belonging to the bacterial β-pore-forming toxin superfamily. Surprisingly, numerous aerolysin-like proteins exist in vertebrates, but their biological functions are unknown. βγ-CAT, a complex of an aerolysin-like protein subunit (two βγ-crystallin domains followed by an aerolysin pore-forming domain) and two trefoil factor subunits, has been identified in frogs (Bombina maxima) skin secretions. Here, we report the rich expression of this protein, in the frog blood and immune-related tissues, and the induction of its presence in peritoneal lavage by bacterial challenge. This phenomena raises the possibility of its involvement in antimicrobial infection. When βγ-CAT was administrated in a peritoneal infection model, it greatly accelerated bacterial clearance and increased the survival rate of both frogs and mice. Meanwhile, accelerated Interleukin-1β release and enhanced local leukocyte recruitments were determined, which may partially explain the robust and effective antimicrobial responses observed. The release of interleukin-1β was potently triggered by βγ-CAT from the frog peritoneal cells and murine macrophages in vitro. βγ-CAT was rapidly endocytosed and translocated to lysosomes, where it formed high molecular mass SDS-stable oligomers (>170 kDa). Lysosomal destabilization and cathepsin B release were detected, which may explain the activation of caspase-1 inflammasome and subsequent interleukin-1β maturation and release. To our knowledge, these results provide the first functional evidence of the ability of a host-derived aerolysin-like protein to counter microbial infection by eliciting rapid and effective host innate immune responses. The findings will also largely help to elucidate the possible involvement and action mechanisms of aerolysin-like proteins and/or trefoil factors widely existing in vertebrates in the host defense against pathogens.

Host and parasite morphology influence congruence between host and parasite phylogenies.

Science.gov (United States)

Sweet, Andrew D; Bush, Sarah E; Gustafsson, Daniel R; Allen, Julie M; DiBlasi, Emily; Skeen, Heather R; Weckstein, Jason D; Johnson, Kevin P

2018-03-23

Comparisons of host and parasite phylogenies often show varying degrees of phylogenetic congruence. However, few studies have rigorously explored the factors driving this variation. Multiple factors such as host or parasite morphology may govern the degree of phylogenetic congruence. An ideal analysis for understanding the factors correlated with congruence would focus on a diverse host-parasite system for increased variation and statistical power. In this study, we focused on the Brueelia-complex, a diverse and widespread group of feather lice that primarily parasitise songbirds. We generated a molecular phylogeny of the lice and compared this tree with a phylogeny of their avian hosts. We also tested for the contribution of each host-parasite association to the overall congruence. The two trees overall were significantly congruent, but the contribution of individual associations to this congruence varied. To understand this variation, we developed a novel approach to test whether host, parasite or biogeographic factors were statistically associated with patterns of congruence. Both host plumage dimorphism and parasite ecomorphology were associated with patterns of congruence, whereas host body size, other plumage traits and biogeography were not. Our results lay the framework for future studies to further elucidate how these factors influence the process of host-parasite coevolution. Copyright © 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Bacterial determinants of importance in the virulence of Gallibacterium anatis in poultry

DEFF Research Database (Denmark)

Persson, Gry; Bojesen, Anders Miki

2015-01-01

immunoglobulins, and hemagglutinins, which may promote biofilm formation are all factors likely linked to the virulence of G. anatis. A major advantage for the study of how G. anatis interact with its host is the ability to perform biologically relevant experimental infections where natural routes of exposure...

Implications for risk assessment of host factors causing large pharmacokinetic variations

Energy Technology Data Exchange (ETDEWEB)

Vesell, E.S.

1985-12-01

Normal human subjects vary widely in their capacity to eliminate many drugs and environmental chemicals. These variations range in magnitude from fourfold to fortyfold depending on the drug and the population studied. Pharmacogenetics deals with only one of many host factors responsible for these large pharmacokinetic differences. Age, sex, diet and exposure to other drugs and chemicals, including oral contraceptives, ethanol and cigarette smoking, can alter the genetically determined rate at which a particular subject eliminates drugs and environmental chemicals. These elimination rates, therefore, are dynamic and change even in the same subject with time and condition. Regulatory legislation has only recently begun to recognize this very broad spectrum of human susceptibility and the existence of multiple special subgroups of particularly sensitive subjects. In setting standards for environmental chemicals, EPA and NIOSH have attempted to protect the most sensitive humans and should be encouraged to continue this policy. For some drugs and environmental chemicals, the commonly used safety factor of 100 may be too low; for these chemicals large, interindividual pharmacokinetic variations produced by pharmacogenetic and other host factors may make a safety factor of 400 or 500 more adequate.

Dual function of the hemagglutinin H5 fused to chicken CD154 in a ...

African Journals Online (AJOL)

Dual function of the hemagglutinin H5 fused to chicken CD154 in a potential strategy of DIVA against avian influenza disease: preliminary study. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like ...

77 FR 63783 - Influenza Viruses Containing the Hemagglutinin from the Goose/Guangdong/1/96 Lineage

Science.gov (United States)

2012-10-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES 42 CFR Part 73 [Docket: CDC-2012-0010] Influenza Viruses... questions concerning highly pathogenic avian influenza (HPAI) H5N1 viruses that contain a hemagglutinin (HA... avian influenza (HPAI) H5N1 viruses with a mortality rate that exceeds 50 percent in hospitalized...

Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls.

NARCIS (Netherlands)

R.A.M. Fouchier (Ron); V.J. Munster (Vincent); A. Wallensten (Anders); T.M. Bestebroer (Theo); S. Herfst (Sander); D.J. Smith (Derek James); G.F. Rimmelzwaan (Guus); B. Olsen (Björn); A.D.M.E. Osterhaus (Albert)

2005-01-01

textabstractIn wild aquatic birds and poultry around the world, influenza A viruses carrying 15 antigenic subtypes of hemagglutinin (HA) and 9 antigenic subtypes of neuraminidase (NA) have been described. Here we describe a previously unidentified antigenic subtype of HA (H16), detected in viruses

Host factors influencing viral persistence

DEFF Research Database (Denmark)

Thomsen, Allan Randrup; Nansen, A; Ørding Andreasen, Susanne

2000-01-01

host were used. Our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. Thus while CD4+ cells are not critical during the initial phase of virus control, infectious virus reappear in mice lacking CD4+ cells, B cells or CD40 ligand...... replication, mice lacking the ability to produce interferon-gamma may develop either a severe, mostly fatal, T-cell mediated wasting syndrome or a chronic infection characterized by long-term coexistence of antiviral cytotoxic T lymphocytes and infectious virus. Mathematical modelling indicates...

The role of carbohydrate in determining the immunochemical properties of the hemagglutinin of influenza A virus

International Nuclear Information System (INIS)

Gitelman, A.K.; Berezin, V.A.; Kharitonenkov, I.G.

1981-01-01

Most of the carbohydrate was removed from influenza with MRC II (H3N2) and its purified hemagglutinin (HA) on treatment with glycosidases, including α-mannosidase, #betta#-N-acetylglucosaminidase, #betta#-galactosidase and α-fucosidase. The release of 50 per cent of the carbohydrate from intact virus particles significantly affected hemagglutinating activity. The ability of untreated and glycosidase-treated virus to inhibit the binding of antibodies directed against the hemagglutinin was almost indistinguishable by competitive radioimmunoassay (RIA). Up to 60 per cent of the carbohydrate from the purified HA of influenza virus could be removed. The antigenicity of glycosidase treated HA molecules decreased 8-fold compared to intact HAs as measured by competitive RIA. In addition, glycosidase digestion of 125 I-labeled HA resulted in a decrease in its reactivity in direct RIA. We conclude that the carbohydrate portion of the HA of influenza virus is not of major importance in defining the antigenicity of HA. (Author)

Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin

Directory of Open Access Journals (Sweden)

Michael B. Doud

2016-06-01

Full Text Available Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.

The Use of Recombinant Hemagglutinine Protein of Rinderpest Virus in Enzyme Immunoassay

OpenAIRE

BULUT, Hakan; BOLAT, Yusuf

2003-01-01

In this study, Rinderpest virus (RPV) recombinant hemagglutinine protein (rH) fused with protein A region of Staphylococcus aureus was expressed in Escherichia coli and purified by IgG affinity chromatography. rH protein was also used to establish enzyme immunoassay. Therefore, to prevent IgG binding to the protein A the wells coated with the rH proteins were blocked by human serum. Afterwards, RPV antigens were added to the wells to evaluate this assay. To this end, serum from mice immunized...

Validation-based insertional mutagenesis for identification of Nup214 as a host factor for EV71 replication in RD cells

International Nuclear Information System (INIS)

Wang, Bei; Zhang, XiaoYu; Zhao, Zhendong

2013-01-01

Highlights: •We introduced a new mutagenesis strategy named VBIM to the viral research. •This method can identify either host factors or host restriction factors. •Using VBIM system, we identified Nup214 as a host factor for EV71 replication in RD cells. -- Abstract: Lentiviral validation-based insertional mutagenesis (VBIM) is a sophisticated, forward genetic approach that is used for the investigation of signal transduction in mammalian cells. Using VBIM, we conducted function-based genetic screening for host genes that affect enterovirus 71 (EV71) viral replication. This included host factors that are required for the life cycle of EV71 and host restriction factors that inhibit EV71 replication. Several cell clones, resistant to EV71, were produced using EV71 infection as a selection pressure and the nuclear pore protein 214 (Nup214) was identified as a host factor required for EV71 replication. In SD2-2, the corresponding VBIM lentivirus transformed clone, the expression of endogenous Nup214 was significantly down-regulated by the reverse inserted VBIM promoter. After Cre recombinase-mediated excision of the VBIM promoter, the expression of Nup214 recovered and the clone regained sensitivity to the EV71 infection. Furthermore, over-expression of Nup214 in the cells suggested that Nup214 was promoting EV71 replication. Results of this study indicate that a successful mutagenesis strategy has been established for screening host genes related to viral replication

Validation-based insertional mutagenesis for identification of Nup214 as a host factor for EV71 replication in RD cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Bei; Zhang, XiaoYu; Zhao, Zhendong, E-mail: timjszzd@163.com

2013-08-02

Highlights: •We introduced a new mutagenesis strategy named VBIM to the viral research. •This method can identify either host factors or host restriction factors. •Using VBIM system, we identified Nup214 as a host factor for EV71 replication in RD cells. -- Abstract: Lentiviral validation-based insertional mutagenesis (VBIM) is a sophisticated, forward genetic approach that is used for the investigation of signal transduction in mammalian cells. Using VBIM, we conducted function-based genetic screening for host genes that affect enterovirus 71 (EV71) viral replication. This included host factors that are required for the life cycle of EV71 and host restriction factors that inhibit EV71 replication. Several cell clones, resistant to EV71, were produced using EV71 infection as a selection pressure and the nuclear pore protein 214 (Nup214) was identified as a host factor required for EV71 replication. In SD2-2, the corresponding VBIM lentivirus transformed clone, the expression of endogenous Nup214 was significantly down-regulated by the reverse inserted VBIM promoter. After Cre recombinase-mediated excision of the VBIM promoter, the expression of Nup214 recovered and the clone regained sensitivity to the EV71 infection. Furthermore, over-expression of Nup214 in the cells suggested that Nup214 was promoting EV71 replication. Results of this study indicate that a successful mutagenesis strategy has been established for screening host genes related to viral replication.

Host transcription factors in the immediate pro-inflammatory response to the parasitic mite Psoroptes ovis.

Directory of Open Access Journals (Sweden)

Stewart T G Burgess

Full Text Available BACKGROUND: Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. We described previously the global host transcriptional response to infestation with P. ovis, elucidating elements of the inflammatory processes which lead to the development of a rapid and profound immune response. However, the mechanisms by which this response is instigated remain unclear. To identify novel methods of intervention a better understanding of the early events involved in triggering the immune response is essential. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response. RESULTS: Through a combination of transcription factor binding site enrichment and pathway analysis we identified key roles for a number of transcription factors in the instigation of cutaneous inflammation. In particular, defined roles were elucidated for the transcription factors NF-kB and AP-1 in the orchestration of the early pro-inflammatory response, with these factors being implicated in the activation of a suite of inflammatory mediators. CONCLUSIONS: Interrogation of the host temporal response to P. ovis infestation has enabled the further identification of the mechanisms underlying the development of the immediate host pro-inflammatory response. This response involves key regulatory roles for the transcription factors NF-kB and AP-1. Pathway analysis demonstrated that the activation of these transcription factors may be triggered following a host LPS-type response, potentially involving TLR4-signalling and also lead to the intriguing possibility that this could be triggered by a P. ovis allergen.

A Trematode Parasite Derived Growth Factor Binds and Exerts Influences on Host Immune Functions via Host Cytokine Receptor Complexes.

Directory of Open Access Journals (Sweden)

Azad A Sulaiman

2016-11-01

Full Text Available The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory receptor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is dependent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs in their evasion of antibody-dependent cell cytotoxicity (ADCC by reducing the NO response of macrophages-again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for dampened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow

Positive Selection on Hemagglutinin and Neuraminidase Genes of H1N1 Influenza Viruses

LENUS (Irish Health Repository)

Li, Wenfu

2011-04-21

Abstract Background Since its emergence in March 2009, the pandemic 2009 H1N1 influenza A virus has posed a serious threat to public health. To trace the evolutionary path of these new pathogens, we performed a selection-pressure analysis of a large number of hemagglutinin (HA) and neuraminidase (NA) gene sequences of H1N1 influenza viruses from different hosts. Results Phylogenetic analysis revealed that both HA and NA genes have evolved into five distinct clusters, with further analyses indicating that the pandemic 2009 strains have experienced the strongest positive selection. We also found evidence of strong selection acting on the seasonal human H1N1 isolates. However, swine viruses from North America and Eurasia were under weak positive selection, while there was no significant evidence of positive selection acting on the avian isolates. A site-by-site analysis revealed that the positively selected sites were located in both of the cleaved products of HA (HA1 and HA2), as well as NA. In addition, the pandemic 2009 strains were subject to differential selection pressures compared to seasonal human, North American swine and Eurasian swine H1N1 viruses. Conclusions Most of these positively and\\/or differentially selected sites were situated in the B-cell and\\/or T-cell antigenic regions, suggesting that selection at these sites might be responsible for the antigenic variation of the viruses. Moreover, some sites were also associated with glycosylation and receptor-binding ability. Thus, selection at these positions might have helped the pandemic 2009 H1N1 viruses to adapt to the new hosts after they were introduced from pigs to humans. Positive selection on position 274 of NA protein, associated with drug resistance, might account for the prevalence of drug-resistant variants of seasonal human H1N1 influenza viruses, but there was no evidence that positive selection was responsible for the spread of the drug resistance of the pandemic H1N1 strains.

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

Science.gov (United States)

Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

2018-04-03

High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication

Directory of Open Access Journals (Sweden)

Julianna Han

2018-04-01

Full Text Available Summary: The emergence of influenza A viruses (IAVs from zoonotic reservoirs poses a great threat to human health. As seasonal vaccines are ineffective against zoonotic strains, and newly transmitted viruses can quickly acquire drug resistance, there remains a need for host-directed therapeutics against IAVs. Here, we performed a genome-scale CRISPR/Cas9 knockout screen in human lung epithelial cells with a human isolate of an avian H5N1 strain. Several genes involved in sialic acid biosynthesis and related glycosylation pathways were highly enriched post-H5N1 selection, including SLC35A1, a sialic acid transporter essential for IAV receptor expression and thus viral entry. Importantly, we have identified capicua (CIC as a negative regulator of cell-intrinsic immunity, as loss of CIC resulted in heightened antiviral responses and restricted replication of multiple viruses. Therefore, our study demonstrates that the CRISPR/Cas9 system can be utilized for the discovery of host factors critical for the replication of intracellular pathogens. : Using a genome-wide CRISPR/Cas9 screen, Han et al. demonstrate that the major hit, the sialic acid transporter SLC35A1, is an essential host factor for IAV entry. In addition, they identify the DNA-binding transcriptional repressor CIC as a negative regulator of cell-intrinsic immunity. Keywords: CRISPR/Cas9 screen, GeCKO, influenza virus, host factors, sialic acid pathway, SLC35A1, Capicua, CIC, cell-intrinsic immunity, H5N1

Impact of sex on prognostic host factors in surgical patients with lung cancer.

Science.gov (United States)

Wainer, Zoe; Wright, Gavin M; Gough, Karla; Daniels, Marissa G; Choong, Peter; Conron, Matthew; Russell, Prudence A; Alam, Naveed Z; Ball, David; Solomon, Benjamin

2017-12-01

Lung cancer has markedly poorer survival in men. Recognized important prognostic factors are divided into host, tumour and environmental factors. Traditional staging systems that use only tumour factors to predict prognosis are of limited accuracy. By examining sex-based patterns of disease-specific survival in non-small cell lung cancer patients, we determined the effect of sex on the prognostic value of additional host factors. Two cohorts of patients treated surgically with curative intent between 2000 and 2009 were utilized. The primary cohort was from Melbourne, Australia, with an independent validation set from the American Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate analyses of validated host-related prognostic factors were performed in both cohorts to investigate the differences in survival between men and women. The Melbourne cohort had 605 patients (61% men) and SEER cohort comprised 55 681 patients (51% men). Disease-specific 5-year survival showed men had statistically significant poorer survival in both cohorts (P < 0.001); Melbourne men at 53.2% compared with women at 68.3%, and SEER 53.3% men and 62.0% women were alive at 5 years. Being male was independently prognostic for disease-specific mortality in the Melbourne cohort after adjustment for ethnicity, smoking history, performance status, age, pathological stage and histology (hazard ratio = 1.54, 95% confidence interval: 1.10-2.16, P = 0.012). Sex differences in non-small cell lung cancer are important irrespective of age, ethnicity, smoking, performance status and tumour, node and metastasis stage. Epidemiological findings such as these should be translated into research and clinical paradigms to determine the factors that influence the survival disadvantage experienced by men. © 2016 Royal Australasian College of Surgeons.

Museum specimens reveal loss of pollen host plants as key factor driving wild bee decline in The Netherlands

Science.gov (United States)

Scheper, Jeroen; Reemer, Menno; van Kats, Ruud; Ozinga, Wim A.; van der Linden, Giel T. J.; Schaminée, Joop H. J.; Siepel, Henk; Kleijn, David

2014-01-01

Evidence for declining populations of both wild and managed bees has raised concern about a potential global pollination crisis. Strategies to mitigate bee loss generally aim to enhance floral resources. However, we do not really know whether loss of preferred floral resources is the key driver of bee decline because accurate assessment of host plant preferences is difficult, particularly for species that have become rare. Here we examine whether population trends of wild bees in The Netherlands can be explained by trends in host plants, and how this relates to other factors such as climate change. We determined host plant preference of bee species using pollen loads on specimens in entomological collections that were collected before the onset of their decline, and used atlas data to quantify population trends of bee species and their host plants. We show that decline of preferred host plant species was one of two main factors associated with bee decline. Bee body size, the other main factor, was negatively related to population trend, which, because larger bee species have larger pollen requirements than smaller species, may also point toward food limitation as a key factor driving wild bee loss. Diet breadth and other potential factors such as length of flight period or climate change sensitivity were not important in explaining twentieth century bee population trends. These results highlight the species-specific nature of wild bee decline and indicate that mitigation strategies will only be effective if they target the specific host plants of declining species. PMID:25422416

Potent Inhibitors against Newcastle Disease Virus Hemagglutinin-Neuraminidase.

Science.gov (United States)

Rota, Paola; La Rocca, Paolo; Piccoli, Marco; Montefiori, Marco; Cirillo, Federica; Olsen, Lars; Orioli, Marica; Allevi, Pietro; Anastasia, Luigi

2018-02-06

Neuraminidase activity is essential for the infection and propagation of paramyxoviruses, including human parainfluenza viruses (hPIVs) and the Newcastle disease virus (NDV). Thus, many inhibitors have been developed based on the 2-deoxy-2,3-didehydro-d-N-acetylneuraminic acid inhibitor (DANA) backbone. Along this line, herein we report a series of neuraminidase inhibitors, having C4 (p-toluenesulfonamido and azido substituents) and C5 (N-perfluorinated chains) modifications to the DANA backbone, resulting in compounds with 5- to 15-fold greater potency than the currently most active compound, the N-trifluoroacetyl derivative of DANA (FANA), toward the NDV hemagglutinin-neuraminidase (NDV-HN). Remarkably, these inhibitors were found to be essentially inactive against the human sialidase NEU3, which is present on the outer layer of the cell membrane and is highly affected by the current NDV inhibitor FANA. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A simple Pichia pastoris fermentation and downstream processing strategy for making recombinant pandemic Swine Origin Influenza a virus Hemagglutinin protein.

Science.gov (United States)

Athmaram, T N; Singh, Anil Kumar; Saraswat, Shweta; Srivastava, Saurabh; Misra, Princi; Kameswara Rao, M; Gopalan, N; Rao, P V L

2013-02-01

The present Influenza vaccine manufacturing process has posed a clear impediment to initiation of rapid mass vaccination against spreading pandemic influenza. New vaccine strategies are therefore needed that can accelerate the vaccine production. Pichia offers several advantages for rapid and economical bulk production of recombinant proteins and, hence, can be attractive alternative for producing an effective influenza HA based subunit vaccine. The recombinant Pichia harboring the transgene was subjected to fed-batch fermentation at 10 L scale. A simple fermentation and downstream processing strategy is developed for high-yield secretory expression of the recombinant Hemagglutinin protein of pandemic Swine Origin Influenza A virus using Pichia pastoris via fed-batch fermentation. Expression and purification were optimized and the expressed recombinant Hemagglutinin protein was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blot and MALDI-TOF analysis. In this paper, we describe a fed-batch fermentation protocol for the secreted production of Swine Influenza A Hemagglutinin protein in the P. pastoris GS115 strain. We have shown that there is a clear relationship between product yield and specific growth rate. The fed-batch fermentation and downstream processing methods optimized in the present study have immense practical application for high-level production of the recombinant H1N1 HA protein in a cost effective way using P. pastoris.

Identification of Xylella fastidiosa antivirulence genes: hemagglutinin adhesins contribute a biofilm maturation to X. fastidios and colonization and attenuate virulence.

Science.gov (United States)

Guilhabert, Magalie R; Kirkpatrick, Bruce C

2005-08-01

Xylella fastidosa, a gram-negative, xylem-limited bacterium, is the causal agent of several economically important plant diseases, including Pierce's disease (PD) and citrus variegated chlorosis (CVC). Until recently, the inability to transform or produce transposon mutants of X. fastidosa had been a major impediment to identifying X. fastidosa genes that mediate pathogen and plant interactions. A random transposon (Tn5) library of X. fastidosa was constructed and screened for mutants showing more severe symptoms and earlier grapevine death (hypervirulence) than did vines infected with the wild type. Seven hypervirulent mutants identified in this screen moved faster and reached higher populations than the wild type in grapevines. These results suggest that X. fastidosa attenuates its virulence in planta and that movement is important in X. fastidosa virulence. The mutated genes were sequenced and none had been described previously as antivirulence genes, although six of them showed similarity with genes of known functions in other organisms. One transposon insertion inactivated a hemagglutinin adhesin gene (PD2118), which we named HxfA. Another mutant in a second putative X. fastidosa hemagglutinin gene, PD1792 (HxfB), was constructed, and further characterization of these hxf mutants suggests that X. fastidosa hemagglutinins mediate contact between X. fastidosa cells, which results in colony formation and biofilm maturation within the xylem vessels.

Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.

Science.gov (United States)

Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A

2016-09-01

The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

Host Cell Restriction Factors that Limit Influenza A Infection

Directory of Open Access Journals (Sweden)

Fernando Villalón-Letelier

2017-12-01

Full Text Available Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs and genes encoding other proteins with antiviral potential. Although hundreds of ISGs have been described, the vast majority have not been functionally characterised. Cellular proteins with putative antiviral activity (hereafter referred to as “restriction factors” can target various steps in the virus life-cycle. In the context of influenza virus infection, restriction factors have been described that target virus entry, genomic replication, translation and virus release. Genome wide analyses, in combination with ectopic overexpression and/or gene silencing studies, have accelerated the identification of restriction factors that are active against influenza and other viruses, as well as providing important insights regarding mechanisms of antiviral activity. Herein, we review current knowledge regarding restriction factors that mediate anti-influenza virus activity and consider the viral countermeasures that are known to limit their impact. Moreover, we consider the strengths and limitations of experimental approaches to study restriction factors, discrepancies between in vitro and in vivo studies, and the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.

Induction of MAP Kinase Homologues during Growth and Morphogenetic Development of Karnal Bunt (Tilletia indica) under the Influence of Host Factor(s) from Wheat Spikes

Science.gov (United States)

Gupta, Atul K.; Seneviratne, J. M.; Joshi, G. K.; Kumar, Anil

2012-01-01

Signaling pathways that activate different mitogen-activated protein kinases (MAPKs) in response to certain environmental conditions, play important role in mating type switching (Fus3) and pathogenicity (Pmk1) in many fungi. In order to determine the roles of such regulatory genes in Tilletia indica, the causal pathogen of Karnal bunt (KB) of wheat, semi-quantitative and quantitative RT-PCR was carried out to isolate and determine the expression of MAP kinase homologues during fungal growth and development under in vitro culture. Maximum expression of TiFus3 and TiPmk1 genes were observed at 14th and 21st days of culture and decreased thereafter. To investigate whether the fungus alters the expression levels of same kinases upon interaction with plants, cultures were treated with 1% of host factors (extracted from S-2 stage of wheat spikes). Such treatment induced the expression of MAPks in time dependent manner compared to the absence of host factors. These results suggest that host factor(s) provide certain signal(s) which activate TiFus3 and TiPmk1 during morphogenetic development of T. indica. The results also provides a clue about the role of host factors in enhancing the disease potential due to induction of MAP kinases involved in fungal development and pathogenecity. PMID:22547988

Yersinia virulence factors - a sophisticated arsenal for combating host defences [version 1; referees: 2 approved

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Steve Atkinson

2016-06-01

Full Text Available The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six ‘effector’ proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen.

KAP1 Is a Host Restriction Factor That Promotes Human Adenovirus E1B-55K SUMO Modification

DEFF Research Database (Denmark)

Bürck, Carolin; Mund, Andreas; Berscheminski, Julia

2016-01-01

Once transported to the replication sites, HAdVs need to assure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly characte......Once transported to the replication sites, HAdVs need to assure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly...... characterized, but represent a decisive moment in establishing a productive infection. Here, we identify a novel host viral restriction factor, KAP1. This heterochromatin associated transcription factor regulates the dynamic organization of host chromatin structure via its ability to influence epigenetic marks...

Host-specific interactions with environmental factors shape the distribution of symbiodinium across the Great Barrier Reef.

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Linda Tonk

Full Text Available The endosymbiotic dinoflagellates (genus Symbiodinium within coral reef invertebrates are critical to the survival of the holobiont. The genetic variability of Symbiodinium may contribute to the tolerance of the symbiotic association to elevated sea surface temperatures (SST. To assess the importance of factors such as the local environment, host identity and biogeography in driving Symbiodinium distributions on reef-wide scales, data from studies on reef invertebrate-Symbiodinium associations from the Great Barrier Reef (GBR were compiled.The resulting database consisted of 3717 entries from 26 studies. It was used to explore ecological patterns such as host-specificity and environmental drivers structuring community complexity using a multi-scalar approach. The data was analyzed in several ways: (i frequently sampled host species were analyzed independently to investigate the influence of the environment on symbiont distributions, thereby excluding the influence of host specificity, (ii host species distributions across sites were added as an environmental variable to determine the contribution of host identity on symbiont distribution, and (iii data were pooled based on clade (broad genetic groups dividing the genus Symbiodinium to investigate factors driving Symbiodinium distributions using lower taxonomic resolution. The results indicated that host species identity plays a dominant role in determining the distribution of Symbiodinium and environmental variables shape distributions on a host species-specific level. SST derived variables (especially SSTstdev most often contributed to the selection of the best model. Clade level comparisons decreased the power of the predictive model indicating that it fails to incorporate the main drivers behind Symbiodinium distributions.Including the influence of different host species on Symbiodinium distributional patterns improves our understanding of the drivers behind the complexity of Symbiodinium

Biosynthesis of measles virus hemagglutinin in persistently infected cells

International Nuclear Information System (INIS)

Bellini, W.J.; Silver, G.D.; McFarlin, D.E.

1983-01-01

The synthesis of the hemagglutinin (HA) glycoprotein of measles virus was investigated in a persistently infected cell line using a monoclonal anti-HA. The synthesis of the HA protein was shown to be associated with the rough endoplasmic reticulum. The unglycosylated (HA 0 ) apoprotein is synthesized as a 65.000 dalton peptide and is inserted into the rough endoplasmic reticulum as a transmembrane protein with approximately 2 to 3000 daltons of the peptide exposed to the cytoplasmic membrane surface. Primary glycosylation of the HA protein was found to occur through the lipid-linked carrier, dolichol-phosphate, as determined by inhibition of glycosylation by tunicamycin. Glycosylation, however, was not a prerequisite for membrane insertion. Endo-β-N-acetyl-Glucosaminidase H digestion of the fully glycosylated HA protein indicated that both simple and complex oligosaccharides are present on the surface glycoprotein. (Author)

[Effects of traditional cooking on antinutritional factors of the black beans (Phaseolus vulgaris) of Costa Rica].

Science.gov (United States)

Bonilla, A R; Calzada, C; Cooke, R

1991-12-01

Trypsin inhibitors, alfa amylase inhibitors and hemagglutinins were determined in black beans (P. vulgaris) produced in Costa Rica. The effect of the traditional cooking on such antinutritional factors was also studied. The antinutritional factors were analyzed spectrophotometrically in the raw beans, as well as after several cooking periods of time. The results showed that alfa-amylase inhibitors were the most thermoresistant. After 30 min of cooking time there was a 33% of activity left from the initial activity of the raw beans. Approximately 80% of the antitryptic activity was destroyed at 9 min of cooking time. After 10 min of cooking time, only 1% of hemagglutinin activity was present.

Shallow Boomerang-shaped Influenza Hemagglutinin G13A Mutant Structure Promotes Leaky Membrane Fusion*

Science.gov (United States)

Lai, Alex L.; Tamm, Lukas K.

2010-01-01

Our previous studies showed that an angled boomerang-shaped structure of the influenza hemagglutinin (HA) fusion domain is critical for virus entry into host cells by membrane fusion. Because the acute angle of ∼105° of the wild-type fusion domain promotes efficient non-leaky membrane fusion, we asked whether different angles would still support fusion and thus facilitate virus entry. Here, we show that the G13A fusion domain mutant produces a new leaky fusion phenotype. The mutant fusion domain structure was solved by NMR spectroscopy in a lipid environment at fusion pH. The mutant adopted a boomerang structure similar to that of wild type but with a shallower kink angle of ∼150°. G13A perturbed the structure of model membranes to a lesser degree than wild type but to a greater degree than non-fusogenic fusion domain mutants. The strength of G13A binding to lipid bilayers was also intermediate between that of wild type and non-fusogenic mutants. These membrane interactions provide a clear link between structure and function of influenza fusion domains: an acute angle is required to promote clean non-leaky fusion suitable for virus entry presumably by interaction of the fusion domain with the transmembrane domain deep in the lipid bilayer. A shallower angle perturbs the bilayer of the target membrane so that it becomes leaky and unable to form a clean fusion pore. Mutants with no fixed boomerang angle interacted with bilayers weakly and did not promote any fusion or membrane perturbation. PMID:20826788

Risk Factors in Host and Environment for Cervicitis Among Commercial Sex Workers

OpenAIRE

Saputra, Nazarwin; Widjanarko, Bagoes; Setyawan, Henry

2016-01-01

sexually transmitted infection (STI) remains a major health problem in some parts of the world. This study aimed to determine the host and environmental factors the effect on the incidence of cervicitis on sex workers. The study was observational case-control design with consecutive sampling technique. Risk factor for cervicitis is a history of sexually transmitted infections (p=0,0001), have couple (boy friend) different gender (p=0,014, OR=4,4; CI95%=1,3-14,3), history of oral sex/cunniling...

Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease.

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Shigeo Hanada

Full Text Available Invasive pneumococcal disease (IPD causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.In a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.Overall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7-12.8, p < .001; age ≥80 years (OR, 6.5; 95% CI, 2.0-21.6, p = .002; serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5-8.1, p < .001; underlying liver disease (OR, 3.5; 95% CI, 1.6-7.8, p = .002; mechanical ventilation (OR, 3.0; 95% CI, 1.7-5.6, p < .001; and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4-4.0, p = .001. Pneumococcal serotype and drug resistance were not associated with poor outcomes.Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.

Host and environmental factors influencing "Candidatus Liberibacter asiaticus" acquisition in Diaphorina citri.

Science.gov (United States)

Wu, Fengnian; Huang, Jiaquan; Xu, Meirong; Fox, Eduardo G P; Beattie, G Andrew C; Holford, Paul; Cen, Yijing; Deng, Xiaoling

2018-05-03

Diaphorina citri is a vector of "Candidatus Liberibacter asiaticus" (CLas) associated with citrus Huanglongbing. In this study, the infection and titers of CLas in the psyllid, were monitored for life cycle stage, sex, host-plant CLas titer, host-plant genotype, and ambient temperature. Acquisition efficiency of CLas by D. citri was highest in nymphs reared at 25 °C on a host plant with high CLas titers but was independent of the host genotypes assessed and of vector sex. We further observed that D. citri nymphs acquired CLas more rapidly than adults based on acquisition access periods (AAPs). CLas did not multiply in the alimentary canal, hemolymph, and salivary glands of adults for 18 d after a 3-day AAP as adult. However, CLas multiplication was detected in hemolymph and salivary gland of adults after the bacterium was acquired by nymphs. Eighty percent of salivary glands of adults contained CLas 18 d after a 3-day AAP as nymph compared to 10% 18 d after a 3-day AAP as adults. Different factors tested herein influenced CLas acquisition efficiency of D. citri, CLas multiplication and spread inside the psyllid. These observations serve to better understand mechanisms of CLas infection in D. citri. This article is protected by copyright. All rights reserved.

The molecular determinants of antibody recognition and antigenic drift in the H3 hemagglutinin of swine influenza A virus

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Influenza A virus (IAV) of the H3 subtype is an important pathogen that affects both humans and swine. The main intervention strategy for preventing infection is vaccination to induce neutralizing antibodies against the surface glycoprotein hemagglutinin (HA). However, due to antigenic drift, vaccin...

Glycosylation of Hemagglutinin and Neuraminidase of Influenza A Virus as Signature for Ecological Spillover and Adaptation among Influenza Reservoirs

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Paul Kim

2018-04-01

Full Text Available Glycosylation of the hemagglutinin (HA and neuraminidase (NA of the influenza provides crucial means for immune evasion and viral fitness in a host population. However, the time-dependent dynamics of each glycosylation sites have not been addressed. We monitored the potential N-linked glycosylation (NLG sites of over 10,000 HA and NA of H1N1 subtype isolated from human, avian, and swine species over the past century. The results show a shift in glycosylation sites as a hallmark of 1918 and 2009 pandemics, and also for the 1976 “abortive pandemic”. Co-segregation of particular glycosylation sites was identified as a characteristic of zoonotic transmission from animal reservoirs, and interestingly, of “reverse zoonosis” of human viruses into swine populations as well. After the 2009 pandemic, recent isolates accrued glycosylation at canonical sites in HA, reflecting gradual seasonal adaptation, and a novel glycosylation in NA as an independent signature for adaptation among humans. Structural predictions indicated a remarkably pleiotropic influence of glycans on multiple HA epitopes for immune evasion, without sacrificing the receptor binding of HA or the activity of NA. The results provided the rationale for establishing the ecological niche of influenza viruses among the reservoir and could be implemented for influenza surveillance and improving pandemic preparedness.

Glycosylation of Hemagglutinin and Neuraminidase of Influenza A Virus as Signature for Ecological Spillover and Adaptation among Influenza Reservoirs

Science.gov (United States)

Kim, Paul; Jang, Yo Han; Kwon, Soon Bin; Lee, Chung Min; Han, Gyoonhee; Seong, Baik Lin

2018-01-01

Glycosylation of the hemagglutinin (HA) and neuraminidase (NA) of the influenza provides crucial means for immune evasion and viral fitness in a host population. However, the time-dependent dynamics of each glycosylation sites have not been addressed. We monitored the potential N-linked glycosylation (NLG) sites of over 10,000 HA and NA of H1N1 subtype isolated from human, avian, and swine species over the past century. The results show a shift in glycosylation sites as a hallmark of 1918 and 2009 pandemics, and also for the 1976 “abortive pandemic”. Co-segregation of particular glycosylation sites was identified as a characteristic of zoonotic transmission from animal reservoirs, and interestingly, of “reverse zoonosis” of human viruses into swine populations as well. After the 2009 pandemic, recent isolates accrued glycosylation at canonical sites in HA, reflecting gradual seasonal adaptation, and a novel glycosylation in NA as an independent signature for adaptation among humans. Structural predictions indicated a remarkably pleiotropic influence of glycans on multiple HA epitopes for immune evasion, without sacrificing the receptor binding of HA or the activity of NA. The results provided the rationale for establishing the ecological niche of influenza viruses among the reservoir and could be implemented for influenza surveillance and improving pandemic preparedness. PMID:29642453

Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus.

Science.gov (United States)

Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori

2016-11-28

H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.

Citizen science data reveal ecological, historical and evolutionary factors shaping interactions between woody hosts and wood-inhabiting fungi.

Science.gov (United States)

Heilmann-Clausen, Jacob; Maruyama, Pietro K; Bruun, Hans Henrik; Dimitrov, Dimitar; Laessøe, Thomas; Frøslev, Tobias Guldberg; Dalsgaard, Bo

2016-12-01

Woody plants host diverse communities of associated organisms, including wood-inhabiting fungi. In this group, host effects on species richness and interaction network structure are not well understood, especially not at large geographical scales. We investigated ecological, historical and evolutionary determinants of fungal species richness and network modularity, that is, subcommunity structure, across woody hosts in Denmark, using a citizen science data set comprising > 80 000 records of > 1000 fungal species on 91 genera of woody plants. Fungal species richness was positively related to host size, wood pH, and the number of species in the host genus, with limited influence of host frequency and host history, that is, time since host establishment in the area. Modularity patterns were unaffected by host history, but largely reflected host phylogeny. Notably, fungal communities differed substantially between angiosperm and gymnosperm hosts. Host traits and evolutionary history appear to be more important than host frequency and recent history in structuring interactions between hosts and wood-inhabiting fungi. High wood acidity appears to act as a stress factor reducing fungal species richness, while large host size, providing increased niche diversity, enhances it. In some fungal groups that are known to interact with live host cells in the establishment phase, host selectivity is common, causing a modular community structure. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Quantitative characterization of glycan-receptor binding of H9N2 influenza A virus hemagglutinin.

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Karunya Srinivasan

Full Text Available Avian influenza subtypes such as H5, H7 and H9 are yet to adapt to the human host so as to establish airborne transmission between humans. However, lab-generated reassorted viruses possessing hemagglutinin (HA and neuraminidase (NA genes from an avian H9 isolate and other genes from a human-adapted (H3 or H1 subtype acquired two amino acid changes in HA and a single amino acid change in NA that confer respiratory droplet transmission in ferrets. We previously demonstrated for human-adapted H1, H2 and H3 subtypes that quantitative binding affinity of their HA to α2→6 sialylated glycan receptors correlates with respiratory droplet transmissibility of the virus in ferrets. Such a relationship remains to be established for H9 HA. In this study, we performed a quantitative biochemical characterization of glycan receptor binding properties of wild-type and mutant forms of representative H9 HAs that were previously used in context of reassorted viruses in ferret transmission studies. We demonstrate here that distinct molecular interactions in the glycan receptor-binding site of different H9 HAs affect the glycan-binding specificity and affinity. Further we show that α2→6 glycan receptor-binding affinity of a mutant H9 HA carrying Thr-189→Ala amino acid change correlates with the respiratory droplet transmission in ferrets conferred by this change. Our findings contribute to a framework for monitoring the evolution of H9 HA by understanding effects of molecular changes in HA on glycan receptor-binding properties.

Cycle Inhibiting Factors (Cifs: Cyclomodulins That Usurp the Ubiquitin-Dependent Degradation Pathway of Host Cells

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Eric Oswald

2011-03-01

Full Text Available Cycle inhibiting factors (Cifs are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are “cyclomodulins” that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions.

Molecular Evolution and Characterization of Hemagglutinin (H in Peste des Petits Ruminants Virus.

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Zhongxiang Liang

Full Text Available Peste des Petits Ruminants (PPR is an acute, highly contagious, and febrile viral disease that affects both domestic and wild small ruminants. The disease has become a major obstacle to the development of sustainable Agriculture. Hemagglutinin (H, the envelope glycoprotein of Peste des Petits Ruminants Virus (PPRV, plays a crucial role in regulating viral adsorption and entry, thus determining pathogenicity, and release of newly produced viral particles. In order to accurately understand the epidemic of the disease and the interactions between the virus and host, we launch the work. Here, we examined H gene from all four lineages of the PPRV to investigate evolutionary and epidemiologic dynamics of PPRV by the Bayesian method. In addition, we predicted positive selection sites due to selective pressures. Finally, we studied the interaction between H protein and SLAM receptor based on homology model of the complex. Phylogenetic analysis suggested that H gene can also be used to investigate evolutionary and epidemiologic dynamics of PPRV. Positive selection analysis identified four positive selection sites in H gene, in which only one common site (aa246 was detected by two methods, suggesting strong operation structural and/or functional constraint of changes on the H protein. This target site may be of interest for future mutagenesis studies. The results of homology modeling showed PPRVHv-shSLAM binding interface and MVH-maSLAM binding interface were consistent, wherein the groove in the B4 blade and B5 of the head domain of PPRVHv bound to the AGFCC' β-sheets of the membrane-distal ectodomain of shSLAM. The binding regions could provide insight on the nature of the protein for epitope vaccine design, novel drug discovery, and rational drug design against PPRV.

Cell-to-Cell Measles Virus Spread between Human Neurons Is Dependent on Hemagglutinin and Hyperfusogenic Fusion Protein.

Science.gov (United States)

Sato, Yuma; Watanabe, Shumpei; Fukuda, Yoshinari; Hashiguchi, Takao; Yanagi, Yusuke; Ohno, Shinji

2018-03-15

Measles virus (MV) usually causes acute infection but in rare cases persists in the brain, resulting in subacute sclerosing panencephalitis (SSPE). Since human neurons, an important target affected in the disease, do not express the known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), how MV infects neurons and spreads between them is unknown. Recent studies have shown that many virus strains isolated from SSPE patients possess substitutions in the extracellular domain of the fusion (F) protein which confer enhanced fusion activity. Hyperfusogenic viruses with such mutations, unlike the wild-type MV, can induce cell-cell fusion even in SLAM- and nectin 4-negative cells and spread efficiently in human primary neurons and the brains of animal models. We show here that a hyperfusogenic mutant MV, IC323-F(T461I)-EGFP (IC323 with a fusion-enhancing T461I substitution in the F protein and expressing enhanced green fluorescent protein), but not the wild-type MV, spreads in differentiated NT2 cells, a widely used human neuron model. Confocal time-lapse imaging revealed the cell-to-cell spread of IC323-F(T461I)-EGFP between NT2 neurons without syncytium formation. The production of virus particles was strongly suppressed in NT2 neurons, also supporting cell-to-cell viral transmission. The spread of IC323-F(T461I)-EGFP was inhibited by a fusion inhibitor peptide as well as by some but not all of the anti-hemagglutinin antibodies which neutralize SLAM- or nectin-4-dependent MV infection, suggesting the presence of a distinct neuronal receptor. Our results indicate that MV spreads in a cell-to-cell manner between human neurons without causing syncytium formation and that the spread is dependent on the hyperfusogenic F protein, the hemagglutinin, and the putative neuronal receptor for MV. IMPORTANCE Measles virus (MV), in rare cases, persists in the human central nervous system (CNS) and causes subacute sclerosing panencephalitis (SSPE) several

Ebola virus host cell entry.

Science.gov (United States)

Sakurai, Yasuteru

2015-01-01

Ebola virus is an enveloped virus with filamentous structure and causes a severe hemorrhagic fever in human and nonhuman primates. Host cell entry is the first essential step in the viral life cycle, which has been extensively studied as one of the therapeutic targets. A virus factor of cell entry is a surface glycoprotein (GP), which is an only essential viral protein in the step, as well as the unique particle structure. The virus also interacts with a lot of host factors to successfully enter host cells. Ebola virus at first binds to cell surface proteins and internalizes into cells, followed by trafficking through endosomal vesicles to intracellular acidic compartments. There, host proteases process GPs, which can interact with an intracellular receptor. Then, under an appropriate circumstance, viral and endosomal membranes are fused, which is enhanced by major structural changes of GPs, to complete host cell entry. Recently the basic research of Ebola virus infection mechanism has markedly progressed, largely contributed by identification of host factors and detailed structural analyses of GPs. This article highlights the mechanism of Ebola virus host cell entry, including recent findings.

Posthodiplostomum cuticola (Digenea: Diplostomatidae) in intermediate fish hosts: factors contributing to the parasite infection and prey selection by the definitive bird host

Czech Academy of Sciences Publication Activity Database

Ondračková, Markéta; Šimková, A.; Gelnar, M.; Jurajda, Pavel

2004-01-01

Roč. 129, č. 6 (2004), s. 761-770 ISSN 0031-1820 R&D Projects: GA ČR GA524/02/0924; GA ČR GP524/03/P108 Institutional research plan: CEZ:AV0Z6093917 Keywords : fish assemblages * intermediate host * complex life-cycle Subject RIV: EG - Zoology Impact factor: 1.685, year: 2004

Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

Science.gov (United States)

Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

2011-01-01

Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody

Energy Technology Data Exchange (ETDEWEB)

Raymond, Donald D.; Bajic, Goran; Ferdman, Jack; Suphaphiphat, Pirada; Settembre, Ethan C.; Moody, M. Anthony; Schmidt, Aaron G.; Harrison, Stephen C. (Duke-MED); (CH-Boston); (Seqirus)

2017-12-18

Antigenic variation requires frequent revision of annual influenza vaccines. Next-generation vaccine design strategies aim to elicit a broader immunity by directing the human immune response toward conserved sites on the principal viral surface protein, the hemagglutinin (HA). We describe a group of antibodies that recognize a hitherto unappreciated, conserved site on the HA of H1 subtype influenza viruses. Mutations in that site, which required a change in the H1 component of the 2017 vaccine, had not previously “taken over” among circulating H1 viruses. Our results encourage vaccine design strategies that resurface a protein to focus the immune response on a specific region.

Host phylogeny determines viral persistence and replication in novel hosts.

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Ben Longdon

2011-09-01

Full Text Available Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

Science.gov (United States)

Gates, R D; Hoegh-Guldberg, O; McFall-Ngai, M J; Bil, K Y; Muscatine, L

1995-08-01

Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation.

Production of polyclonal antibody against Tehran strain influenza virus (A/H1N1/2009 hemagglutinin conserved domain (HA2: brief report

Directory of Open Access Journals (Sweden)

Somayeh Zamani

2015-10-01

Full Text Available Background: The influenza virus is one of the most important factors for higher morbidity and mortality in the world. Recently, researchers have been focused on influenza conserved antigenic proteins such as hemagglutinin stalk domain (HA2 for vaccine production and serological studies. The HA2 plays a major role in the fusion of the virus with host cells membrane. The immunity system enables to produce antibody against HA2. The aim of this study is polyclonal antibody production against influenza HA2. Methods: This study was done in the Influenza Research Lab, Pasteur Institute of Iran, Tehran for one year from September 2013 to October 2014. In the present study, recombinant HA2 protein was produced in prokaryotic system and purified using Nickel affinity chromatography. The purified HA2 was mixed with Freund’s adjuvant (complete and incomplete and injected into two New Zealand white rabbits by intramuscularly and subcutaneously routes. Immunization was continued for several months with two weeks interval. Before each immunization, blood was drawn by venous puncture from the rabbit ear. Function of rabbit's sera was evaluated using radial immunodiffusion (RID in both forms, Single RID (SRID and Double RID (DRID. Finally, antiserum activity against HA2 was evaluated using western blotting as serological assay. Results: Sedimentary line and zone was observed in RID assays (SRID and DRID represent interaction between HA2 protein and anti- HA2 antibody. As well as, western blotting results was positive for HA2 protein. Therefore, these results showed that polyclonal antibody produced against HA2 protein can identify HA2 protein antigenic sites. Conclusion: These findings show that humoral immune responses have properly been stimulated in rabbits and these antibodies can identify HA2 protein and may be suitable for other serological methods.

Factors affecting patterns of Amblyomma triste (Acari: Ixodidae) parasitism in a rodent host.

Science.gov (United States)

Colombo, Valeria C; Nava, Santiago; Antoniazzi, Leandro R; Monje, Lucas D; Racca, Andrea L; Guglielmone, Alberto A; Beldomenico, Pablo M

2015-07-30

Here we offer a multivariable analysis that explores associations of different factors (i.e., environmental, host parameters, presence of other ectoparasites) with the interaction of Amblyomma triste immature stages and one of its main hosts in Argentina, the rodent Akodon azarae. Monthly and for two years, we captured and sampled rodents at 16 points located at 4 different sites in the Parana River Delta region. The analyses were conducted with Generalized Linear Mixed Models with a negative binomial response (counts of larvae or nymphs). The independent variables assessed were: (a) environmental: trapping year, season, presence of cattle; type of vegetation (natural grassland or implanted forest); rodent abundance; (b) host parameters: body length; sex; body condition; blood cell counts; natural antibody titres; and (c) co-infestation with other ectoparasites: other stage of A. triste; Ixodes loricatus; lice; mites; and fleas. Two-way interaction terms deemed a priori as relevant were also included in the analysis. Larvae were affected by all environmental variables assessed and by the presence of other ectoparasites (lice, fleas and other tick species). Host factors significantly associated with larval count were sex and levels of natural antibodies. Nymphs were associated with season, presence of cattle, body condition, body length and with burdens of I. loricatus. In most cases, the direction and magnitude of the associations were context-dependent (many interaction terms were significant). The findings of greater significance and implications of our study are two. Firstly, as burdens of A. triste larvae and nymphs were greater where cattle were present, and larval tick burdens were higher in implanted forests, silvopastoral practices developing in the region may affect the population dynamics of A. triste, and consequently the eco-epidemiology of Rickettsia parkeri. Secondly, strong associations and numerous interactions with other ectoparasites suggest that

Location of Host and Host Habitat by Fruit Fly Parasitoids

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Pascal Rousse

2012-11-01

Full Text Available Augmentative releases of parasitoids may be a useful tool for the area-wide management of tephritid pests. The latter are parasitized by many wasp species, though only a few of them are relevant for augmentative biocontrol purposes. To date, nearly all the actual or potential biocontrol agents for such programs are egg or larval Opiinae parasitoids (Hymenoptera: Braconidae. Here, we review the literature published on their habitat and host location behavior, as well as the factors that modulate this behavior, which is assumed to be sequential; parasitoids forage first for the host habitat and then for the host itself. Parasitoids rely on chemical, visual, and mechanical stimuli, often strongly related to their ecology. Behavioral modulation factors include biotic and abiotic factors including learning, climatic conditions and physiological state of the insect. Finally, conclusions and perspectives for future research are briefly highlighted. A detailed knowledge of this behavior may be very useful for selecting the release sites for both inundative/augmentative releases of mass-reared parasitoids and inoculative releases for classical biocontrol.

Computation of Hemagglutinin Free Energy Difference by the Confinement Method

Science.gov (United States)

2017-01-01

Hemagglutinin (HA) mediates membrane fusion, a crucial step during influenza virus cell entry. How many HAs are needed for this process is still subject to debate. To aid in this discussion, the confinement free energy method was used to calculate the conformational free energy difference between the extended intermediate and postfusion state of HA. Special care was taken to comply with the general guidelines for free energy calculations, thereby obtaining convergence and demonstrating reliability of the results. The energy that one HA trimer contributes to fusion was found to be 34.2 ± 3.4kBT, similar to the known contributions from other fusion proteins. Although computationally expensive, the technique used is a promising tool for the further energetic characterization of fusion protein mechanisms. Knowledge of the energetic contributions per protein, and of conserved residues that are crucial for fusion, aids in the development of fusion inhibitors for antiviral drugs. PMID:29151344

[Serum immunoglobulin IgG subclass distribution of antibody responses to pertussis toxin and filamentous hemagglutinin of Bordetella pertussis in patients with whooping cough].

Science.gov (United States)

Rastawicki, Waldemar; Smietańska, Karolina; Rokosz-Chudziak, Natalia; Jagielski, Marek

2013-01-01

The present study was aimed at determining the IgG subclass distribution against pertussis toxin (PT) and filamentous hemagglutinin (FHA) of Bordetella pertussis in patients with whooping cough. The total number of 222 serum samples obtained from patients suspected in clinical investigation for pertussis were tested separately by in-house ELISA for the presence of IgG antibodies to pertussis toxin and filamentous hemagglutinin. The percentage distribution of specific anti-PT and anti-FHA IgG subclass response was calculated only on the basis of group of sera confirmed in the present study as positive for total IgG antibodies (183 sera to PT antigen and 129 to FHA antigen). Paired serum specimens were obtained from 36 patients. Based on the results of determining the level of antibodies in the sera of 40 blood donors, the cut-off limit of serum antibodies for each subclass was set at arithmetic mean plus two standard deviations. Antibodies of IgG1 to pertussis toxin and filamentous hemagglutinin were diagnosed in 151 (82.5%) and 99 (76.7%), IgG2 in 72 (39.0%) and 50 (38.8%), IgG3 in 17 (9.3%) and 43 (33.3%), IgG4 in 55 (30.1%) and 53 (41.1%) serum samples, respectively. There were no significant differences in percentage of sera with IgG1, IgG2 and IgG3 in relation to age of the patients. However, the frequency of occurrence of IgG4 antibodies was highest in the group of the youngest children to the age of 6 years old (61.8% for PT and 68.0% for FHA), and decrease with age, reaching the minimum in the group of patients above 40 years old (13.2% and 4.2% for PT and FHA, respectively). We also found significantly higher frequency of IgG4 to PT and FHA antigens in men than in women. Statistically significant, essential changes in the pattern of IgG subclass during the course of infection were not found. In conclusion, this study showed that all four subclasses of IgG antibodies to pertussis toxin and filamentous hemagglutinin are produced during whooping cough.

Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants.

Science.gov (United States)

Jutras, Philippe V; D'Aoust, Marc-André; Couture, Manon M-J; Vézina, Louis-Philippe; Goulet, Marie-Claire; Michaud, Dominique; Sainsbury, Frank

2015-09-01

Eukaryotic expression systems are used for the production of complex secreted proteins. However, recombinant proteins face considerable biochemical challenges along the secretory pathway, including proteolysis and pH variation between organelles. As the use of synthetic biology matures into solutions for protein production, various host-cell engineering approaches are being developed to ameliorate host-cell factors that can limit recombinant protein quality and yield. We report the potential of the influenza M2 ion channel as a novel tool to neutralize the pH in acidic subcellular compartments. Using transient expression in the plant host, Nicotiana benthamiana, we show that ion channel expression can significantly raise pH in the Golgi apparatus and that this can have a strong stabilizing effect on a fusion protein separated by an acid-susceptible linker peptide. We exemplify the utility of this effect in recombinant protein production using influenza hemagglutinin subtypes differentially stable at low pH; the expression of hemagglutinins prone to conformational change in mildly acidic conditions is considerably enhanced by M2 co-expression. The co-expression of a heterologous ion channel to stabilize acid-labile proteins and peptides represents a novel approach to increasing the yield and quality of secreted recombinant proteins in plants and, possibly, in other eukaryotic expression hosts. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microscopy-based Assays for High-throughput Screening of Host Factors Involved in Brucella Infection of Hela Cells.

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Casanova, Alain; Low, Shyan H; Emmenlauer, Mario; Conde-Alvarez, Raquel; Salcedo, Suzana P; Gorvel, Jean-Pierre; Dehio, Christoph

2016-08-05

Brucella species are facultative intracellular pathogens that infect animals as their natural hosts. Transmission to humans is most commonly caused by direct contact with infected animals or by ingestion of contaminated food and can lead to severe chronic infections. Brucella can invade professional and non-professional phagocytic cells and replicates within endoplasmic reticulum (ER)-derived vacuoles. The host factors required for Brucella entry into host cells, avoidance of lysosomal degradation, and replication in the ER-like compartment remain largely unknown. Here we describe two assays to identify host factors involved in Brucella entry and replication in HeLa cells. The protocols describe the use of RNA interference, while alternative screening methods could be applied. The assays are based on the detection of fluorescently labeled bacteria in fluorescently labeled host cells using automated wide-field microscopy. The fluorescent images are analyzed using a standardized image analysis pipeline in CellProfiler which allows single cell-based infection scoring. In the endpoint assay, intracellular replication is measured two days after infection. This allows bacteria to traffic to their replicative niche where proliferation is initiated around 12 hr after bacterial entry. Brucella which have successfully established an intracellular niche will thus have strongly proliferated inside host cells. Since intracellular bacteria will greatly outnumber individual extracellular or intracellular non-replicative bacteria, a strain constitutively expressing GFP can be used. The strong GFP signal is then used to identify infected cells. In contrast, for the entry assay it is essential to differentiate between intracellular and extracellular bacteria. Here, a strain encoding for a tetracycline-inducible GFP is used. Induction of GFP with simultaneous inactivation of extracellular bacteria by gentamicin enables the differentiation between intracellular and extracellular

Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements.

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Olga V Viktorovskaya

2016-08-01

Full Text Available There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses replication.Seventy-nine novel RNA binding proteins for dengue virus (DENV were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps

Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

International Nuclear Information System (INIS)

Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin

2016-01-01

In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

Energy Technology Data Exchange (ETDEWEB)

Lee, Yoon Jae [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Jang, Yo Han [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Kim, Paul; Lee, Yun Ha; Lee, Young Jae [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Seong, Baik Lin, E-mail: blseong@yonsei.ac.kr [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of)

2016-04-15

In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

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.

Science.gov (United States)

Nuss, Jonathan E; Kehn-Hall, Kylene; Benedict, Ashwini; Costantino, Julie; Ward, Michael; Peyser, Brian D; Retterer, Cary J; Tressler, Lyal E; Wanner, Laura M; McGovern, Hugh F; Zaidi, Anum; Anthony, Scott M; Kota, Krishna P; Bavari, Sina; Hakami, Ramin M

2014-01-01

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.

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.

Directory of Open Access Journals (Sweden)

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.

Energy transfer between a nanosystem and its host fluid: A multiscale factorization approach

Science.gov (United States)

Sereda, Yuriy V.; Espinosa-Duran, John M.; Ortoleva, Peter J.

2014-02-01

Energy transfer between a macromolecule or supramolecular assembly and a host medium is considered from the perspective of Newton's equations and Lie-Trotter factorization. The development starts by demonstrating that the energy of the molecule evolves slowly relative to the time scale of atomic collisions-vibrations. The energy is envisioned to be a coarse-grained variable that coevolves with the rapidly fluctuating atomistic degrees of freedom. Lie-Trotter factorization is shown to be a natural framework for expressing this coevolution. A mathematical formalism and workflow for efficient multiscale simulation of energy transfer is presented. Lactoferrin and human papilloma virus capsid-like structure are used for validation.

Energy transfer between a nanosystem and its host fluid: A multiscale factorization approach

Energy Technology Data Exchange (ETDEWEB)

Sereda, Yuriy V.; Espinosa-Duran, John M.; Ortoleva, Peter J., E-mail: ortoleva@indiana.edu [Center for Cell and Virus Theory, Department of Chemistry, Indiana University, 800 E. Kirkwood Ave, Bloomington, Indiana 47405 (United States)

2014-02-21

Energy transfer between a macromolecule or supramolecular assembly and a host medium is considered from the perspective of Newton's equations and Lie-Trotter factorization. The development starts by demonstrating that the energy of the molecule evolves slowly relative to the time scale of atomic collisions-vibrations. The energy is envisioned to be a coarse-grained variable that coevolves with the rapidly fluctuating atomistic degrees of freedom. Lie-Trotter factorization is shown to be a natural framework for expressing this coevolution. A mathematical formalism and workflow for efficient multiscale simulation of energy transfer is presented. Lactoferrin and human papilloma virus capsid-like structure are used for validation.

Energy transfer between a nanosystem and its host fluid: A multiscale factorization approach

International Nuclear Information System (INIS)

Sereda, Yuriy V.; Espinosa-Duran, John M.; Ortoleva, Peter J.

2014-01-01

Energy transfer between a macromolecule or supramolecular assembly and a host medium is considered from the perspective of Newton's equations and Lie-Trotter factorization. The development starts by demonstrating that the energy of the molecule evolves slowly relative to the time scale of atomic collisions-vibrations. The energy is envisioned to be a coarse-grained variable that coevolves with the rapidly fluctuating atomistic degrees of freedom. Lie-Trotter factorization is shown to be a natural framework for expressing this coevolution. A mathematical formalism and workflow for efficient multiscale simulation of energy transfer is presented. Lactoferrin and human papilloma virus capsid-like structure are used for validation

Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense?

NARCIS (Netherlands)

van der Poll, T.; Lowry, S. F.

1995-01-01

Tumor necrosis factor-alpha (TNF) exerts numerous influences which, in association with severe infection, subserve both detrimental as well as beneficial host responses. The current review addresses recent insights into the structure and function of this pleiotropic cytokine, with a particular

CD151, a novel host factor of nuclear export signaling in influenza virus infection.

Science.gov (United States)

Qiao, Yongkang; Yan, Yan; Tan, Kai Sen; Tan, Sheryl S L; Seet, Ju Ee; Arumugam, Thiruma Valavan; Chow, Vincent T K; Wang, De Yun; Tran, Thai

2018-05-01

Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro-differentiated human nasal epithelial cells cultured at air-liquid interface. As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Comparative study of the hemagglutinin and neuraminidase genes of influenza A virus H3N2, H9N2, and H5N1 subtypes using bioinformatics techniques.

Science.gov (United States)

Ahn, Insung; Son, Hyeon S

2007-07-01

To investigate the genomic patterns of influenza A virus subtypes, such as H3N2, H9N2, and H5N1, we collected 1842 sequences of the hemagglutinin and neuraminidase genes from the NCBI database and parsed them into 7 categories: accession number, host species, sampling year, country, subtype, gene name, and sequence. The sequences that were isolated from the human, avian, and swine populations were extracted and stored in a MySQL database for intensive analysis. The GC content and relative synonymous codon usage (RSCU) values were calculated using JAVA codes. As a result, correspondence analysis of the RSCU values yielded the unique codon usage pattern (CUP) of each subtype and revealed no extreme differences among the human, avian, and swine isolates. H5N1 subtype viruses exhibited little variation in CUPs compared with other subtypes, suggesting that the H5N1 CUP has not yet undergone significant changes within each host species. Moreover, some observations may be relevant to CUP variation that has occurred over time among the H3N2 subtype viruses isolated from humans. All the sequences were divided into 3 groups over time, and each group seemed to have preferred synonymous codon patterns for each amino acid, especially for arginine, glycine, leucine, and valine. The bioinformatics technique we introduce in this study may be useful in predicting the evolutionary patterns of pandemic viruses.

Relevance of genetically determined host factors to the prognosis of meningococcal disease.

Science.gov (United States)

Domingo, P; Muñiz-Diaz, E; Baraldès, M A; Arilla, M; Barquet, N; Pericas, R; Juárez, C; Madoz, P; Vázquez, G

2004-08-01

To assess the relevance of genetically determined host factors for the prognosis of meningococcal disease, Fc gamma receptor IIA (FcgammaRIIA), the tumor necrosis factor alpha (TNF-alpha) gene promoter region, and plasminogen-activator-inhibitor-1 (PAI-1) gene polymorphisms were studied in 145 patients with meningococcal disease and in 290 healthy controls matched by sex. Distribution of FcgammaRIIA, TNF-alpha, and PAI-1 alleles was not significantly different between patients and controls. Patients with the FcgammaRIIA-R/R 131 allotype scored > or =1 point in the Barcelona prognostic system more frequently than patients with other allotypes (odds ratio, 18.6; 95% confidence interval, 7.1-49.0, PFc gamma receptor IIA polymorphism was associated with markers of disease severity, but TNF-alpha and PAI-1 polymorphisms were not.

Inhibition of Avian Influenza A Virus Replication in Human Cells by Host Restriction Factor TUFM Is Correlated with Autophagy.

Science.gov (United States)

Kuo, Shu-Ming; Chen, Chi-Jene; Chang, Shih-Cheng; Liu, Tzu-Jou; Chen, Yi-Hsiang; Huang, Sheng-Yu; Shih, Shin-Ru

2017-06-13

Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2 627 E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2 627 K (human signature) and PB2 627 E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2 627 E than PB2 627 K in transfected human cells. Stronger binding of TUFM to avian-signature PB2 590 G/ 591 Q and PB2 627 E in the 2009 swine-origin pandemic H1N1 and 2013 avian-origin H7N9 influenza A viruses was similarly observed. Viruses carrying avian-signature PB2 627 E demonstrated increased replication in TUFM-deficient cells, but viral replication decreased in cells overexpressing TUFM. Interestingly, the presence of TUFM specifically inhibited the replication of PB2 627 E viruses, but not PB2 627 K viruses. In addition, enhanced levels of interaction between TUFM and PB2 627 E were noted in the mitochondrial fraction of infected cells. Furthermore, TUFM-dependent autophagy was reduced in TUFM-deficient cells infected with PB2 627 E virus; however, autophagy remained consistent in PB2 627 K virus-infected cells. The results suggest that TUFM acts as a host restriction factor that impedes avian-signature influenza A virus replication in human cells in a manner that correlates with autophagy. IMPORTANCE An understanding of the mechanisms that influenza A viruses utilize to shift host tropism and the identification of host restriction factors that can limit infection are both

Uveal melanoma in relation to ultraviolet light exposure and host factors.

Science.gov (United States)

Holly, E A; Aston, D A; Char, D H; Kristiansen, J J; Ahn, D K

1990-09-15

We conducted a case-control interview study among 1277 subjects (407 patients, 870 controls selected by using random digit dial) in 11 western United States to determine whether uveal melanoma and cutaneous melanoma shared common risk factors. After adjustment for other factors, the risk of uveal melanoma was increased for those with green, gray, or hazel eyes [relative risk (RR) = 2.5, P less than 0.001] or blue eyes (RR = 2.2, P less than 0.001) when compared to brown. A tendency to sunburn after 0.5 h midday summer sun exposure increased risk for uveal melanoma (burn with tanning RR = 1.5, P = 0.02; burn with little tanning RR = 1.8, P less than 0.001; burn with no tanning RR = 1.7, P = 0.002); as did exposure to UV or black lights (RR = 3.7, P = 0.003); and welding burn, sunburn of the eye, or snow blindness (RR = 7.2, P less than 0.001). An association with uveal melanoma was also noted with an increasing number of large nevi (P = 0.04 for trend), although the individual risk estimates were not remarkable. These data suggest that host factors and exposure to UV light are risk factors for uveal melanoma.

Airway protease/antiprotease imbalance in atopic asthmatics contributes to increased influenza A virus cleavage and replication

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Asthmatics are more susceptible to influenza infections, yet mechanisms mediating this enhanced susceptibility are unknown. Influenza virus hemagglutinin (HA) protein binds to sialic add residues on the host cells. HA requires cleavage to allow fusion of the viral HA with host ce...

Poxvirus Host Range Genes and Virus-Host Spectrum: A Critical Review.

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Oliveira, Graziele Pereira; Rodrigues, Rodrigo Araújo Lima; Lima, Maurício Teixeira; Drumond, Betânia Paiva; Abrahão, Jônatas Santos

2017-11-07

The Poxviridae family is comprised of double-stranded DNA viruses belonging to nucleocytoplasmic large DNA viruses (NCLDV). Among the NCLDV, poxviruses exhibit the widest known host range, which is likely observed because this viral family has been more heavily investigated. However, relative to each member of the Poxviridae family, the spectrum of the host is variable, where certain viruses can infect a large range of hosts, while others are restricted to only one host species. It has been suggested that the variability in host spectrum among poxviruses is linked with the presence or absence of some host range genes. Would it be possible to extrapolate the restriction of viral replication in a specific cell lineage to an animal, a far more complex organism? In this study, we compare and discuss the relationship between the host range of poxvirus species and the abundance/diversity of host range genes. We analyzed the sequences of 38 previously identified and putative homologs of poxvirus host range genes, and updated these data with deposited sequences of new poxvirus genomes. Overall, the term host range genes might not be the most appropriate for these genes, since no correlation between them and the viruses' host spectrum was observed, and a change in nomenclature should be considered. Finally, we analyzed the evolutionary history of these genes, and reaffirmed the occurrence of horizontal gene transfer (HGT) for certain elements, as previously suggested. Considering the data presented in this study, it is not possible to associate the diversity of host range factors with the amount of hosts of known poxviruses, and this traditional nomenclature creates misunderstandings.

Poxvirus Host Range Genes and Virus–Host Spectrum: A Critical Review

Science.gov (United States)

Oliveira, Graziele Pereira; Rodrigues, Rodrigo Araújo Lima; Lima, Maurício Teixeira; Drumond, Betânia Paiva; Abrahão, Jônatas Santos

2017-01-01

The Poxviridae family is comprised of double-stranded DNA viruses belonging to nucleocytoplasmic large DNA viruses (NCLDV). Among the NCLDV, poxviruses exhibit the widest known host range, which is likely observed because this viral family has been more heavily investigated. However, relative to each member of the Poxviridae family, the spectrum of the host is variable, where certain viruses can infect a large range of hosts, while others are restricted to only one host species. It has been suggested that the variability in host spectrum among poxviruses is linked with the presence or absence of some host range genes. Would it be possible to extrapolate the restriction of viral replication in a specific cell lineage to an animal, a far more complex organism? In this study, we compare and discuss the relationship between the host range of poxvirus species and the abundance/diversity of host range genes. We analyzed the sequences of 38 previously identified and putative homologs of poxvirus host range genes, and updated these data with deposited sequences of new poxvirus genomes. Overall, the term host range genes might not be the most appropriate for these genes, since no correlation between them and the viruses’ host spectrum was observed, and a change in nomenclature should be considered. Finally, we analyzed the evolutionary history of these genes, and reaffirmed the occurrence of horizontal gene transfer (HGT) for certain elements, as previously suggested. Considering the data presented in this study, it is not possible to associate the diversity of host range factors with the amount of hosts of known poxviruses, and this traditional nomenclature creates misunderstandings. PMID:29112165

Host-bacterial interplay in periodontal disease

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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.

Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

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Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

2007-04-01

Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

Within-Host Evolution of Human Influenza Virus.

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Xue, Katherine S; Moncla, Louise H; Bedford, Trevor; Bloom, Jesse D

2018-03-10

The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution. Copyright © 2018 Elsevier Ltd. All rights reserved.

H1N1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.

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Marion Russier

2017-03-01

Full Text Available A pandemic-capable influenza virus requires a hemagglutinin (HA surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5.1 to 5.9 for H1 viruses and pH 5.3 to 5.8 for H3 viruses. Thus, contemporary swine isolates vary widely in HA stability, having values favored by both avian (pH >5.5 and human and ferret (pH ≤5.5 species. Using an early 2009 pandemic H1N1 (pH1N1 virus backbone, we generated three viruses differing by one HA residue that only altered HA stability: WT (pH 5.5, HA1-Y17H (pH 6.0, and HA2-R106K (pH 5.3. All three replicated in pigs and transmitted from pig-to-pig and pig-to-ferret. WT and R106 viruses maintained HA genotype and phenotype after transmission. Y17H (pH 6.0 acquired HA mutations that stabilized the HA protein to pH 5.8 after transmission to pigs and 5.5 after transmission to ferrets. Overall, we found swine support a broad range of HA activation pH for contact transmission and many recent swine H1N1 and H3N2 isolates have stabilized (human-like HA proteins. This constitutes a heightened pandemic risk and underscores the importance of ongoing surveillance and control efforts for swine viruses.

The Impact of Host Metabolic Factors on Treatment Outcome in Chronic Hepatitis C

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Savvidou Savvoula

2012-01-01

Full Text Available Background. Recent data suggest that chronic hepatitis C has to be considered a metabolic disease further to a viral infection. The aim of this study was to elaborate on the complex interactions between hepatitis C virus, host metabolic factors, and treatment response. Methods. Demographic, virological, and histological data from 356 consecutive patients were analyzed retrospectively. Hepatic steatosis, obesity, and insulin resistance were examined in relation to their impact on treatment outcome. Comparison between genotype 1 and 3 patients was performed to identify differences in the determinants of hepatic steatosis. Results. Histological evidence of hepatic steatosis was found in 113 patients, distributed in 20.3%, 9.0%, and 2.5% for grades I, II, and III, respectively. Hepatic steatosis was associated with past alcohol abuse (P=0.003 and histological evidence of advanced fibrosis (P<0.001. Older age (OR 2.51, P=0.002, genotype (OR 3.28, P<0.001, cirrhosis (OR 4.23, P=0.005, and hepatic steatosis (OR 2.48, P=0.001 were independent predictors for nonresponse. Correlations of hepatic steatosis with alcohol, insulin resistance, and fibrosis stage were found similar for both genotypes 1 and 3. Conclusions. Host metabolic factors may predict treatment outcome, and this impact remains significant even in genotype 3, where steatosis has been believed to be exclusively virus related.

A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses

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Macken, Catherine A.; Lewis, Nicola S.; Van Reeth, Kristien; Brown, Ian H.; Swenson, Sabrina L.; Simon, Gaëlle; Saito, Takehiko; Berhane, Yohannes; Ciacci-Zanella, Janice; Pereda, Ariel; Davis, C. Todd; Donis, Ruben O.; Webby, Richard J.

2016-01-01

ABSTRACT The H1 subtype of influenza A viruses (IAVs) has been circulating in swine since the 1918 human influenza pandemic. Over time, and aided by further introductions from nonswine hosts, swine H1 viruses have diversified into three genetic lineages. Due to limited global data, these H1 lineages were named based on colloquial context, leading to a proliferation of inconsistent regional naming conventions. In this study, we propose rigorous phylogenetic criteria to establish a globally consistent nomenclature of swine H1 virus hemagglutinin (HA) evolution. These criteria applied to a data set of 7,070 H1 HA sequences led to 28 distinct clades as the basis for the nomenclature. We developed and implemented a web-accessible annotation tool that can assign these biologically informative categories to new sequence data. The annotation tool assigned the combined data set of 7,070 H1 sequences to the correct clade more than 99% of the time. Our analyses indicated that 87% of the swine H1 viruses from 2010 to the present had HAs that belonged to 7 contemporary cocirculating clades. Our nomenclature and web-accessible classification tool provide an accurate method for researchers, diagnosticians, and health officials to assign clade designations to HA sequences. The tool can be updated readily to track evolving nomenclature as new clades emerge, ensuring continued relevance. A common global nomenclature facilitates comparisons of IAVs infecting humans and pigs, within and between regions, and can provide insight into the diversity of swine H1 influenza virus and its impact on vaccine strain selection, diagnostic reagents, and test performance, thereby simplifying communication of such data. IMPORTANCE A fundamental goal in the biological sciences is the definition of groups of organisms based on evolutionary history and the naming of those groups. For influenza A viruses (IAVs) in swine, understanding the hemagglutinin (HA) genetic lineage of a circulating strain aids

Kallistatin Ameliorates Influenza Virus Pathogenesis by Inhibition of Kallikrein-Related Peptidase 1-Mediated Cleavage of Viral Hemagglutinin

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Leu, Chia-Hsing; Yang, Mei-Lin; Chung, Nai-Hui; Huang, Yen-Jang; Su, Yu-Chu; Chen, Yi-Cheng; Lin, Chia-Cheng; Shieh, Gia-Shing; Chang, Meng-Ya; Wang, Shainn-Wei; Chang, Yao; Chao, Julie; Chao, Lee

2015-01-01

Proteolytic cleavage of the hemagglutinin (HA) of influenza virus by host trypsin-like proteases is required for viral infectivity. Some serine proteases are capable of cleaving influenza virus HA, whereas some serine protease inhibitors (serpins) inhibit the HA cleavage in various cell types. Kallikrein-related peptidase 1 (KLK1, also known as tissue kallikrein) is a widely distributed serine protease. Kallistatin, a serpin synthesized mainly in the liver and rapidly secreted into the circulation, forms complexes with KLK1 and inhibits its activity. Here, we investigated the roles of KLK1 and kallistatin in influenza virus infection. We show that the levels of KLK1 increased, whereas those of kallistatin decreased, in the lungs of mice during influenza virus infection. KLK1 cleaved H1, H2, and H3 HA molecules and consequently enhanced viral production. In contrast, kallistatin inhibited KLK1-mediated HA cleavage and reduced viral production. Cells transduced with the kallistatin gene secreted kallistatin extracellularly, which rendered them more resistant to influenza virus infection. Furthermore, lentivirus-mediated kallistatin gene delivery protected mice against lethal influenza virus challenge by reducing the viral load, inflammation, and injury in the lung. Taking the data together, we determined that KLK1 and kallistatin contribute to the pathogenesis of influenza virus by affecting the cleavage of the HA peptide and inflammatory responses. This study provides a proof of principle for the potential therapeutic application of kallistatin or other KLK1 inhibitors for influenza. Since proteolytic activation also enhances the infectivity of some other viruses, kallistatin and other kallikrein inhibitors may be explored as antiviral agents against these viruses. PMID:26149981

A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria.

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Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

2016-07-29

Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens.

Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase.

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Pavlova, Sophia P; Veits, Jutta; Keil, Günther M; Mettenleiter, Thomas C; Fuchs, Walter

2009-01-29

Attenuated vaccine strains of the alphaherpesvirus causing infectious laryngotracheitis of chickens (ILTV, gallid herpesvirus 1) can be used for mass application. Previously, we showed that live virus vaccination with recombinant ILTV expressing hemagglutinin of highly pathogenic avian influenza viruses (HPAIV) protected chickens against ILT and fowl plague caused by HPAIV carrying the corresponding hemagglutinin subtypes [Lüschow D, Werner O, Mettenleiter TC, Fuchs W. Protection of chickens from lethal avian influenza A virus infection by live-virus vaccination with infectious laryngotracheitis virus recombinants expressing the hemagglutinin (H5) gene. Vaccine 2001;19(30):4249-59; Veits J, Lüschow D, Kindermann K, Werner O, Teifke JP, Mettenleiter TC, et al. Deletion of the non-essential UL0 gene of infectious laryngotracheitis (ILT) virus leads to attenuation in chickens, and UL0 mutants expressing influenza virus haemagglutinin (H7) protect against ILT and fowl plague. J Gen Virol 2003;84(12):3343-52]. However, protection against H5N1 HPAIV was not satisfactory. Therefore, a newly designed dUTPase-negative ILTV vector was used for rapid insertion of the H5-hemagglutinin, or N1-neuraminidase genes of a recent H5N1 HPAIV isolate. Compared to our previous constructs, protein expression was considerably enhanced by insertion of synthetic introns downstream of the human cytomegalovirus immediate-early promoter within the 5'-nontranslated region of the transgenes. Deletion of the viral dUTPase gene did not affect in vitro replication of the ILTV recombinants, but led to sufficient attenuation in vivo. After a single ocular immunization, all chickens developed H5- or N1-specific serum antibodies. Nevertheless, animals immunized with N1-ILTV died after subsequent H5N1 HPAIV challenge, although survival times were prolonged compared to non-vaccinated controls. In contrast, all chickens vaccinated with either H5-ILTV alone, or H5- and N1-ILTV simultaneously, survived

An induced pocket for the binding of potent fusion inhibitor CL-385319 with H5N1 influenza virus hemagglutinin.

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Runming Li

Full Text Available The influenza glycoprotein hemagglutinin (HA plays crucial roles in the early stage of virus infection, including receptor binding and membrane fusion. Therefore, HA is a potential target for developing anti-influenza drugs. Recently, we characterized a novel inhibitor of highly pathogenic H5N1 influenza virus, CL-385319, which specifically inhibits HA-mediated viral entry. Studies presented here identified the critical binding residues for CL-385319, which clustered in the stem region of the HA trimer by site-directed mutagenesis. Extensive computational simulations, including molecular docking, molecular dynamics simulations, molecular mechanics generalized Born surface area (MM_GBSA calculations, charge density and Laplacian calculations, have been carried out to uncover the detailed molecular mechanism that underlies the binding of CL-385319 to H5N1 influenza virus HA. It was found that the recognition and binding of CL-385319 to HA proceeds by a process of "induced fit" whereby the binding pocket is formed during their interaction. Occupation of this pocket by CL-385319 stabilizes the neutral pH structure of hemagglutinin, thus inhibiting the conformational rearrangements required for membrane fusion. This "induced fit" pocket may be a target for structure-based design of more potent influenza fusion inhibitors.

Identifying antigenicity-associated sites in highly pathogenic H5N1 influenza virus hemagglutinin by using sparse learning.

OpenAIRE

Cai, Zhipeng; Yang, Jialiang; Zhang, Tong; Long, Li-Ping; Boon, Adrianus C; Webby, Richard J; Wan, Xiu-Feng

2012-01-01

Since the isolation of A/goose/Guangdong/1/1996 (H5N1) in farmed geese in southern China, highly pathogenic H5N1 avian influenza viruses have posed a continuous threat to both public and animal health. The non-synonymous mutation of the H5 hemagglutinin (HA) gene has resulted in antigenic drift, leading to difficulties in both clinical diagnosis and vaccine strain selection. Characterizing H5N1's antigenic profiles would help resolve these problems. In this study, a novel sparse learning meth...

Viral and Host Factors Required for Avian H5N1 Influenza A Virus Replication in Mammalian Cells

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Hong Zhang

2013-06-01

Full Text Available Following the initial and sporadic emergence into humans of highly pathogenic avian H5N1 influenza A viruses in Hong Kong in 1997, we have come to realize the potential for avian influenza A viruses to be transmitted directly from birds to humans. Understanding the basic viral and cellular mechanisms that contribute to infection of mammalian species with avian influenza viruses is essential for developing prevention and control measures against possible future human pandemics. Multiple physical and functional cellular barriers can restrict influenza A virus infection in a new host species, including the cell membrane, the nuclear envelope, the nuclear environment, and innate antiviral responses. In this review, we summarize current knowledge on viral and host factors required for avian H5N1 influenza A viruses to successfully establish infections in mammalian cells. We focus on the molecular mechanisms underpinning mammalian host restrictions, as well as the adaptive mutations that are necessary for an avian influenza virus to overcome them. It is likely that many more viral and host determinants remain to be discovered, and future research in this area should provide novel and translational insights into the biology of influenza virus-host interactions.

Dietary Factors Modulate Colonic Tumorigenesis Through the Interaction of Gut Microbiota and Host Chloride Channels.

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Zhang, Yong; Kang, Chao; Wang, Xiao-Lan; Zhou, Min; Chen, Meng-Ting; Zhu, Xiao-Hui; Liu, Kai; Wang, Bin; Zhang, Qian-Yong; Zhu, Jun-Dong; Mi, Man-Tian

2018-03-01

In recent decades, the association among diet, gut microbiota, and the risk of colorectal cancer (CRC) has been established. Gut microbiota and associated metabolites, such as bile acids and butyrate, are now known to play a key role in CRC development. The aim of this study is to identify that the progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat diet, or different dose of dihydromyricetin (DMY) interacted with gut microbiota. An AOM/DSS (azoxymethan/dextran sodium sulfate) model is established to study the gut microbiota compsition before and after tumor formation during colitis-induced tumorigenesis. All above dietary factors profoundly influence the composition of gut microbiota and host colonic tumorigenesis. In addition, mice with DMY-modified initial microbiota display different degrees of chemically induced tumorigenesis. Mechanism analysis reveals that gut microbiota-associated chloride channels participated in colon tumorigenesis. Gut microbiota changes occur in the hyperproliferative stage before tumor formation. Gut microbiota and host chloride channels, both of which are regulated by dietary factors, are associated with CRC development. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Macrophage Migration Inhibitory Factor Contributes to Host Defense against Acute Trypanosoma cruzi Infection

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Reyes, José L.; Terrazas, Luis I.; Espinoza, Bertha; Cruz-Robles, David; Soto, Virgilia; Rivera-Montoya, Irma; Gómez-García, Lorena; Snider, Heidi; Satoskar, Abhay R.; Rodríguez-Sosa, Miriam

2006-01-01

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is involved in the host defense against several pathogens. Here we used MIF−/− mice to determine the role of endogenous MIF in the regulation of the host immune response against Trypanosoma cruzi infection. MIF−/− mice displayed high levels of blood and tissue parasitemia, developed severe heart and skeletal muscle immunopathology, and succumbed to T. cruzi infection faster than MIF+/+ mice. The enhanced susceptibility of MIF−/− mice to T. cruzi was associated with reduced levels of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-12 (IL-12), IL-18, gamma interferon (IFN-γ), and IL-1β, in their sera and reduced production of IL-12, IFN-γ, and IL-4 by spleen cells during the early phase of infection. At all time points, antigen-stimulated splenocytes from MIF+/+ and MIF−/− mice produced comparable levels of IL-10. MIF−/− mice also produced significantly less Th1-associated antigen-specific immunoglobulin G2a (IgG2a) throughout the infection, but both groups produced comparable levels of Th2-associated IgG1. Lastly, inflamed hearts from T. cruzi-infected MIF−/− mice expressed increased transcripts for IFN-γ, but fewer for IL-12 p35, IL-12 p40, IL-23, and inducible nitric oxide synthase, compared to MIF+/+ mice. Taken together, our findings show that MIF plays a role in controlling acute T. cruzi infection. PMID:16714544

Prevalence of inter-appointment endodontic flare-ups and host-related factors.

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Azim, Adham A; Azim, Katharina A; Abbott, Paul V

2017-04-01

The aims of this study were to report the prevalence of inter-appointment flare-ups following adequate root canal disinfection and to investigate the host factors contributing to its occurrence. One thousand five hundred patient records were reviewed and the prevalence of flare-up was recorded. Patients' root canal space status (vital, non-vital or retreatment), medical condition and demographics (age, gender, tooth type and position) were recorded from their dental records. Statistical analyses were performed to determine the impact of the recorded factors on flare-up occurrence. Nine hundred fifty-one patient records met the inclusion criteria. The prevalence of flare-up was 2.3 %. There was a correlation between the canal space status and patient's age with flare-up development (P flare-up occurrence and tooth type, location, gender or medical condition (P > 0.5). The root canal space status was the primary factor affecting flare-up occurrence. Patients >50 years had the highest risk in developing flare-ups. This article provides evidence that patients suffering from inflamed pulp will not develop flare-up if adequate cleaning and shaping of the root canal space was performed. It also shows that patients above the age of 50 are a high-risk group that is prone to flare-up development.

Genome-Wide Search for Host Association Factors during Ovine Progressive Pneumonia Virus Infection.

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Jesse Thompson

Full Text Available Ovine progressive pneumonia virus (OPPV is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known restriction factors from other viral infections, a number of factors which may be specific for OPPV infection were uncovered. The data from this RNA-seq study will be helpful in our understanding of OPPV infection, and also for further study in the prevention and intervention of this viral disease.

Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

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Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

2012-01-01

Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

Identifying antigenicity associated sites in highly pathogenic H5N1 influenza virus hemagglutinin by using sparse learning

OpenAIRE

Cai, Zhipeng; Ducatez, Mariette F.; Yang, Jialiang; Zhang, Tong; Long, Li-Ping; Boon, Adrianus C.; Webby, Richard J.; Wan, Xiu-Feng

2012-01-01

Since the isolation of A/goose/Guangdong/1/1996 (H5N1) in farmed geese in southern China, highly pathogenic H5N1 avian influenza viruses have posed a continuous threat to both public and animal health. The non-synonymous mutation of the H5 hemagglutinin gene has resulted in antigenic drift, leading to difficulties in both clinical diagnosis and vaccine strain selection. Characterizing H5N1’s antigenic profiles would help resolve these problems. In this study, a novel sparse learning method wa...

Biotic mortality factors affecting emerald ash borer (Agrilus planipennis) are highly dependent on life stage and host tree crown condition.

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Jennings, D E; Duan, J J; Shrewsbury, P M

2015-10-01

Emerald ash borer (EAB), Agrilus planipennis, is a serious invasive forest pest in North America responsible for killing tens to hundreds of millions of ash trees since it was accidentally introduced in the 1990 s. Although host-plant resistance and natural enemies are known to be important sources of mortality for EAB in Asia, less is known about the importance of different sources of mortality at recently colonized sites in the invaded range of EAB, and how these relate to host tree crown condition. To further our understanding of EAB population dynamics, we used a large-scale field experiment and life-table analyses to quantify the fates of EAB larvae and the relative importance of different biotic mortality factors at 12 recently colonized sites in Maryland. We found that the fates of larvae were highly dependent on EAB life stage and host tree crown condition. In relatively healthy trees (i.e., with a low EAB infestation) and for early instars, host tree resistance was the most important mortality factor. Conversely, in more unhealthy trees (i.e., with a moderate to high EAB infestation) and for later instars, parasitism and predation were the major sources of mortality. Life-table analyses also indicated how the lack of sufficient levels of host tree resistance and natural enemies contribute to rapid population growth of EAB at recently colonized sites. Our findings provide further evidence of the mechanisms by which EAB has been able to successfully establish and spread in North America.

Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

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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

Host molecular factors and viral genotypes in the mother-to-child HIV-1 transmission in sub-Saharan Africa

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Linda Chapdeleine M. Mouafo

2017-07-01

Full Text Available Maternal viral load and immune status, timing and route of delivery, viral subtype, and host genetics are known to influence the transmission, acquisition and disease progression of human immunodeficiency virus-1 (HIV-1 infection. This review summarizes the findings from published works on host molecular factors and virus genotypes affecting mother to child transmission (MTCT in Africa and identifies the gaps that need to be addressed in future research. Articles in PubMed, Google and AIDSearch and relevant conference abstracts publications were searched. Accessible articles on host factors and viral genetics impacting the MTCT of HIV, done on African populations till 2015 were downloaded. Forty-six articles were found and accessed; 70% described host genes impacting the transmission. The most studied gene was the CCR5 promoter, followed by the CCR2-64I found to reduce MTCT; then SDF1-3’A shown to have no effect on MTCT and others like the DC-SIGNR, CD4, CCL3 and IP- 10. The HLA class I was most studied and was generally linked to the protective effect on MTCT. Breast milk constituents were associated to protection against MTCT. However, existing studies in Sub Saharan Africa were done just in few countries and some done without control groups. Contradictory results obtained may be due to different genetic background, type of controls, different socio-cultural and economic environment and population size. More studies are thus needed to better understand the mechanism of transmission or prevention.

Risk Factors in Host and Environment for Cervicitis Among Commercial Sex Workers

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Nazarwin Saputra

2017-09-01

Full Text Available sexually transmitted infection (STI remains a major health problem in some parts of the world. This study aimed to determine the host and environmental factors the effect on the incidence of cervicitis on sex workers. The study was observational case-control design with consecutive sampling technique. Risk factor for cervicitis is a history of sexually transmitted infections (p=0,0001, have couple (boy friend different gender (p=0,014, OR=4,4; CI95%=1,3-14,3, history of oral sex/cunnilingus (p=0,003, OR=6,8;CI95%=1,9-24,8, smokers (p=0,0001, CI95%=5,6; CI95%=2,4-13,1. Condom use last sex behavior is a protective factor affecting the incidence of cervicitis (p=0,0001, OR= 0,198; CI95 %=0,07- 0,5. The conclusion of this study is to prevent servisitis at-risk groups of commercial sex workers it should avoid from exposure of agents that cause sexually transmitted infections, does not have a spouse who is not authorized (girlfriend that leads to sex behavior, avoid behaviors oral sex / cunnilingus, no smoke. At-risk behavior should use condoms for prevention servisitis

The role of host genetic factors in respiratory tract infectious diseases: systematic review, meta-analyses and field synopsis

NARCIS (Netherlands)

Patarčić, Inga; Gelemanović, Andrea; Kirin, Mirna; Kolčić, Ivana; Theodoratou, Evropi; Baillie, Kenneth J.; de Jong, Menno D.; Rudan, Igor; Campbell, Harry; Polašek, Ozren

2015-01-01

Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of

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

[Validation of the modified algorithm for predicting host susceptibility to viruses taking into account susceptibility parameters of primary target cell cultures and natural immunity factors].

Science.gov (United States)

Zhukov, V A; Shishkina, L N; Safatov, A S; Sergeev, A A; P'iankov, O V; Petrishchenko, V A; Zaĭtsev, B N; Toporkov, V S; Sergeev, A N; Nesvizhskiĭ, Iu V; Vorob'ev, A A

2010-01-01

The paper presents results of testing a modified algorithm for predicting virus ID50 values in a host of interest by extrapolation from a model host taking into account immune neutralizing factors and thermal inactivation of the virus. The method was tested for A/Aichi/2/68 influenza virus in SPF Wistar rats, SPF CD-1 mice and conventional ICR mice. Each species was used as a host of interest while the other two served as model hosts. Primary lung and trachea cells and secretory factors of the rats' airway epithelium were used to measure parameters needed for the purpose of prediction. Predicted ID50 values were not significantly different (p = 0.05) from those experimentally measured in vivo. The study was supported by ISTC/DARPA Agreement 450p.

Host Ecology Rather Than Host Phylogeny Drives Amphibian Skin Microbial Community Structure in the Biodiversity Hotspot of Madagascar

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Bletz, Molly C.; Archer, Holly; Harris, Reid N.; McKenzie, Valerie J.; Rabemananjara, Falitiana C. E.; Rakotoarison, Andolalao; Vences, Miguel

2017-01-01

Host-associated microbiotas of vertebrates are diverse and complex communities that contribute to host health. In particular, for amphibians, cutaneous microbial communities likely play a significant role in pathogen defense; however, our ecological understanding of these communities is still in its infancy. Here, we take advantage of the fully endemic and locally species-rich amphibian fauna of Madagascar to investigate the factors structuring amphibian skin microbiota on a large scale. Using amplicon-based sequencing, we evaluate how multiple host species traits and site factors affect host bacterial diversity and community structure. Madagascar is home to over 400 native frog species, all of which are endemic to the island; more than 100 different species are known to occur in sympatry within multiple rainforest sites. We intensively sampled frog skin bacterial communities, from over 800 amphibians from 89 species across 30 sites in Madagascar during three field visits, and found that skin bacterial communities differed strongly from those of the surrounding environment. Richness of bacterial operational taxonomic units (OTUs) and phylogenetic diversity differed among host ecomorphs, with arboreal frogs exhibiting lower richness and diversity than terrestrial and aquatic frogs. Host ecomorphology was the strongest factor influencing microbial community structure, with host phylogeny and site parameters (latitude and elevation) explaining less but significant portions of the observed variation. Correlation analysis and topological congruency analyses revealed little to no phylosymbiosis for amphibian skin microbiota. Despite the observed geographic variation and low phylosymbiosis, we found particular OTUs that were differentially abundant between particular ecomorphs. For example, the genus Pigmentiphaga (Alcaligenaceae) was significantly enriched on arboreal frogs, Methylotenera (Methylophilaceae) was enriched on aquatic frogs, and Agrobacterium (Rhizobiaceae

Host Ecology Rather Than Host Phylogeny Drives Amphibian Skin Microbial Community Structure in the Biodiversity Hotspot of Madagascar

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Molly C. Bletz

2017-08-01

Full Text Available Host-associated microbiotas of vertebrates are diverse and complex communities that contribute to host health. In particular, for amphibians, cutaneous microbial communities likely play a significant role in pathogen defense; however, our ecological understanding of these communities is still in its infancy. Here, we take advantage of the fully endemic and locally species-rich amphibian fauna of Madagascar to investigate the factors structuring amphibian skin microbiota on a large scale. Using amplicon-based sequencing, we evaluate how multiple host species traits and site factors affect host bacterial diversity and community structure. Madagascar is home to over 400 native frog species, all of which are endemic to the island; more than 100 different species are known to occur in sympatry within multiple rainforest sites. We intensively sampled frog skin bacterial communities, from over 800 amphibians from 89 species across 30 sites in Madagascar during three field visits, and found that skin bacterial communities differed strongly from those of the surrounding environment. Richness of bacterial operational taxonomic units (OTUs and phylogenetic diversity differed among host ecomorphs, with arboreal frogs exhibiting lower richness and diversity than terrestrial and aquatic frogs. Host ecomorphology was the strongest factor influencing microbial community structure, with host phylogeny and site parameters (latitude and elevation explaining less but significant portions of the observed variation. Correlation analysis and topological congruency analyses revealed little to no phylosymbiosis for amphibian skin microbiota. Despite the observed geographic variation and low phylosymbiosis, we found particular OTUs that were differentially abundant between particular ecomorphs. For example, the genus Pigmentiphaga (Alcaligenaceae was significantly enriched on arboreal frogs, Methylotenera (Methylophilaceae was enriched on aquatic frogs, and Agrobacterium

Host Ecology Rather Than Host Phylogeny Drives Amphibian Skin Microbial Community Structure in the Biodiversity Hotspot of Madagascar.

Science.gov (United States)

Bletz, Molly C; Archer, Holly; Harris, Reid N; McKenzie, Valerie J; Rabemananjara, Falitiana C E; Rakotoarison, Andolalao; Vences, Miguel

2017-01-01

Host-associated microbiotas of vertebrates are diverse and complex communities that contribute to host health. In particular, for amphibians, cutaneous microbial communities likely play a significant role in pathogen defense; however, our ecological understanding of these communities is still in its infancy. Here, we take advantage of the fully endemic and locally species-rich amphibian fauna of Madagascar to investigate the factors structuring amphibian skin microbiota on a large scale. Using amplicon-based sequencing, we evaluate how multiple host species traits and site factors affect host bacterial diversity and community structure. Madagascar is home to over 400 native frog species, all of which are endemic to the island; more than 100 different species are known to occur in sympatry within multiple rainforest sites. We intensively sampled frog skin bacterial communities, from over 800 amphibians from 89 species across 30 sites in Madagascar during three field visits, and found that skin bacterial communities differed strongly from those of the surrounding environment. Richness of bacterial operational taxonomic units (OTUs) and phylogenetic diversity differed among host ecomorphs, with arboreal frogs exhibiting lower richness and diversity than terrestrial and aquatic frogs. Host ecomorphology was the strongest factor influencing microbial community structure, with host phylogeny and site parameters (latitude and elevation) explaining less but significant portions of the observed variation. Correlation analysis and topological congruency analyses revealed little to no phylosymbiosis for amphibian skin microbiota. Despite the observed geographic variation and low phylosymbiosis, we found particular OTUs that were differentially abundant between particular ecomorphs. For example, the genus Pigmentiphaga (Alcaligenaceae) was significantly enriched on arboreal frogs, Methylotenera (Methylophilaceae) was enriched on aquatic frogs, and Agrobacterium (Rhizobiaceae

Gnarled-trunk evolutionary model of influenza A virus hemagglutinin.

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Kimihito Ito

Full Text Available Human influenza A viruses undergo antigenic changes with gradual accumulation of amino acid substitutions on the hemagglutinin (HA molecule. A strong antigenic mismatch between vaccine and epidemic strains often requires the replacement of influenza vaccines worldwide. To establish a practical model enabling us to predict the future direction of the influenza virus evolution, relative distances of amino acid sequences among past epidemic strains were analyzed by multidimensional scaling (MDS. We found that human influenza viruses have evolved along a gnarled evolutionary pathway with an approximately constant curvature in the MDS-constructed 3D space. The gnarled pathway indicated that evolution on the trunk favored multiple substitutions at the same amino acid positions on HA. The constant curvature was reasonably explained by assuming that the rate of amino acid substitutions varied from one position to another according to a gamma distribution. Furthermore, we utilized the estimated parameters of the gamma distribution to predict the amino acid substitutions on HA in subsequent years. Retrospective prediction tests for 12 years from 1997 to 2009 showed that 70% of actual amino acid substitutions were correctly predicted, and that 45% of predicted amino acid substitutions have been actually observed. Although it remains unsolved how to predict the exact timing of antigenic changes, the present results suggest that our model may have the potential to recognize emerging epidemic strains.

Host DNA synthesis-suppressing factor in culture fluid of tissue cultures infected with measles virus

International Nuclear Information System (INIS)

Minagawa, T.; Nakaya, C.; Iida, H.

1974-01-01

Host DNA synthesis is suppressed by the culture fluid of cell cultures infected with measles virus. This activity in the culture fluid is initiated somewhat later than the growth of infectious virus. Ninety percent of host DNA synthesis in HeLa cells is inhibited by culture fluid of 3-day-old cell cultures of Vero or HeLa cells infected with measles virus. This suppressing activity is not a property of the virion, but is due to nonvirion-associated componentnent which shows none of the activities of measles virus such as hemagglutination, hemolysis, or cell fusion nor does it have the antigenicity of measles virus as tested by complement-fixation or hemagglutination-inhibiting antibody blocking tests. Neutralization of the activity of this component is not attained with the pooled sera of convalescent measles patients. This component has molecular weights of about 45,000, 20,000, and 3,000 and appears to be a heat-stable protein. The production of host DNA suppressing factor (DSF) is blocked by cycloheximide. Neither uv-inactivated nor antiserum-neutralized measles virus produce DSF. Furthermore, such activity of nonvirion-associated component is not detected in the culture fluid of cultures infected with other RNA viruses such as poliovirus, vesicular stomatitis virus, or Sindbis virus. (auth)

The host plant metabolite glucose is the precursor of diffusible signal factor (DSF) family signals in Xanthomonas campestris.

Science.gov (United States)

Deng, Yinyue; Liu, Xiaoling; Wu, Ji'en; Lee, Jasmine; Chen, Shaohua; Cheng, Yingying; Zhang, Chunyan; Zhang, Lian-Hui

2015-04-01

Plant pathogen Xanthomonas campestris pv. campestris produces cis-11-methyl-2-dodecenoic acid (diffusible signal factor [DSF]) as a cell-cell communication signal to regulate biofilm dispersal and virulence factor production. Previous studies have demonstrated that DSF biosynthesis is dependent on the presence of RpfF, an enoyl-coenzyme A (CoA) hydratase, but the DSF synthetic mechanism and the influence of the host plant on DSF biosynthesis are still not clear. We show here that exogenous addition of host plant juice or ethanol extract to the growth medium of X. campestris pv. campestris could significantly boost DSF family signal production. It was subsequently revealed that X. campestris pv. campestris produces not only DSF but also BDSF (cis-2-dodecenoic acid) and another novel DSF family signal, which was designated DSF-II. BDSF was originally identified in Burkholderia cenocepacia to be involved in regulation of motility, biofilm formation, and virulence in B. cenocepacia. Functional analysis suggested that DSF-II plays a role equal to that of DSF in regulation of biofilm dispersion and virulence factor production in X. campestris pv. campestris. Furthermore, chromatographic separation led to identification of glucose as a specific molecule stimulating DSF family signal biosynthesis in X. campestris pv. campestris. (13)C-labeling experiments demonstrated that glucose acts as a substrate to provide a carbon element for DSF biosynthesis. The results of this study indicate that X. campestris pv. campestris could utilize a common metabolite of the host plant to enhance DSF family signal synthesis and therefore promote virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genetic Characterization of the Hemagglutinin Genes of Wild-Type Measles Virus Circulating in China, 1993–2009

Science.gov (United States)

Zhu, Zhen; Liu, Chunyu; Mao, Naiying; Ji, Yixin; Wang, Huiling; Jiang, Xiaohong; Li, Chongshan; Tang, Wei; Feng, Daxing; Wang, Changyin; Zheng, Lei; Lei, Yue; Ling, Hua; Zhao, Chunfang; Ma, Yan; He, Jilan; Wang, Yan; Li, Ping; Guan, Ronghui; Zhou, Shujie; Zhou, Jianhui; Wang, Shuang; Zhang, Hong; Zheng, Huanying; Liu, Leng; Ma, Hemuti; Guan, Jing; Lu, Peishan; Feng, Yan; Zhang, Yanjun; Zhou, Shunde; Xiong, Ying; Ba, Zhuoma; Chen, Hui; Yang, Xiuhui; Bo, Fang; Ma, Yujie; Liang, Yong; Lei, Yake; Gu, Suyi; Liu, Wei; Chen, Meng; Featherstone, David; Jee, Youngmee; Bellini, William J.; Rota, Paul A.; Xu, Wenbo

2013-01-01

Background China experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies. Principal Findings Analysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993–2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10−3 substitutions per site per year, and the ratio of dN to dS (dN/dS) was measles in China. PMID:24073194

Time resolved bovine host reponse to virulence factors mapped in milk by selected reaction monitoring

DEFF Research Database (Denmark)

Bislev, Stine Lønnerup; Kusebauch, Ulrike; Codrea, Marius Cosmin

. In this study, we present a sensitive selected reaction monitoring (SRM) proteomics approach, targeting proteins suggested to play key roles in the bovine host response to mastitis. 17 biomarker candidates related to inflammatory response and mastitis were selected. The 17 candidate proteins were quantified......TIME RESOLVED BOVINE HOST RESPONSE TO VIRULENCE FACTORS, MAPPED IN MILK BY SELECTED REACTION MONITORING S.L. Bislev1, U. Kusebauch2, M.C. Codrea1, R. Moritz2, C.M. Røntved1, E. Bendixen1 1 Department of Animal Science, Faculty of Science and Technology, Aarhus University, Tjele, Denmark; 2...... Institute for Systems Biology, Seattle, Washington, USA Mastitis is beyond doubt the largest health problem in modern milk production. Many different pathogens can cause infections in the mammary gland, and give rise to severe toll on animal welfare, economic gain as well as on excessive use of antibiotics...

Human Coronavirus HKU1 Spike Protein Uses O-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme.

Science.gov (United States)

Huang, Xingchuan; Dong, Wenjuan; Milewska, Aleksandra; Golda, Anna; Qi, Yonghe; Zhu, Quan K; Marasco, Wayne A; Baric, Ralph S; Sims, Amy C; Pyrc, Krzysztof; Li, Wenhui; Sui, Jianhua

2015-07-01

Human coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only one with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that is unique to the group a betacoronaviruses (group 2a). The function of HKU1-HE remains largely undetermined. In this study, we examined binding of the S1 domain of hCoV-HKU1 spike to a panel of cells and found that the S1 could specifically bind on the cell surface of a human rhabdomyosarcoma cell line, RD. Pretreatment of RD cells with neuraminidase (NA) and trypsin greatly reduced the binding, suggesting that the binding was mediated by sialic acids on glycoproteins. However, unlike other group 2a CoVs, e.g., hCoV-OC43, for which 9-O-acetylated sialic acid (9-O-Ac-Sia) serves as a receptor determinant, HKU1-S1 bound with neither 9-O-Ac-Sia-containing glycoprotein(s) nor rat and mouse erythrocytes. Nonetheless, the HKU1-HE was similar to OC43-HE, also possessed sialate-O-acetylesterase activity, and acted as a receptor-destroying enzyme (RDE) capable of eliminating the binding of HKU1-S1 to RD cells, whereas the O-acetylesterase-inactive HKU1-HE mutant lost this capacity. Using primary human ciliated airway epithelial (HAE) cell cultures, the only in vitro replication model for hCoV-HKU1 infection, we confirmed that pretreatment of HAE cells with HE but not the enzymatically inactive mutant blocked hCoV-HKU1 infection. These results demonstrate that hCoV-HKU1 exploits O-Ac-Sia as a cellular attachment receptor determinant to initiate the infection of host cells and that its HE protein possesses the corresponding sialate-O-acetylesterase RDE activity. Human coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic

Host preference of the bean weevil Zabrotes subfasciatus

Institute of Scientific and Technical Information of China (English)

Isabel Ribeiro do Valle Teixeira; Angel Roberto Barchuk; Fernando Sérgio Zucoloto

2008-01-01

It is largely known that the range of an insect diet is mostly determined by oviposition behavior, mainly in species with endophytic larvae such as Zabrotes subfasciatus.However, the proximate factors determining host choice and the subsequent steps leading to the expansion or reduction of the host number and occasional host shifts are largelyun known. We analyzed various factors determining host preference of Z. subfasciatus through the evaluation of: (i) oviposition preference of a wild population of Z. subfasciatus on the usual host (bean) and unusual hosts (lentil, chickpea and soy), and the performance of the offspring; (ii) artificial selection for increasing preference for hosts initially less frequently chosen; (iii) comparison of oviposition behavior between two different popula-tions (reared for～30 generations in beans or chickpeas, respectively); (iv) oviposition timing on usual and unusual hosts; and (v) identification of preference hierarchies. We found that when using unusual hosts, there is no correlation between performance and preference and that the preference hierarchy changes only slightly when the population passes through several generations on the less frequently accepted host. We also found a positive response to artificial selection for increasing oviposition on the less preferred host; however, when the host-choice experiment involved two varieties of the usual host, the response was faster than when the choice involved usual and unusual hosts. Finally, beetles reared on an unusual host (chickpea) for 26 generations showed similar good fitness on both usual and unusual hosts,indicating that the use of a new host does not necessarily result in the loss of performance on the original host. Nevertheless, this population showed lower fitness on the usual host than that of the original population, suggesting an underlying partial trade-off phenomenon which may contribute to a broadening of diet of this insect species.

Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria

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Wood Robin

2012-02-01

Full Text Available Abstract Background Detection of lipoarabinomannan (LAM, a Mycobacterium tuberculosis (Mtb cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection. Methods LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay. Results 32/199 (16.1% of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and Conclusions Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection.

THE BIOTIC FACTOR OF TREMATOD OPISTHORHIS FELINEUS INVASION INFLUENCE ON HOST IMMUNE STATUS AND SOMATIC CELLS PROLIFERATIVE ACTIVITY

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A. G. Rybka

2016-01-01

Full Text Available The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

Genetic Factors in Rhizobium Affecting the Symbiotic Carbon Costs of N2 Fixation and Host Plant Biomass Production

DEFF Research Database (Denmark)

Skøt, L.; Hirsch, P. R.; Witty, J. F.

1986-01-01

The effect of genetic factors in Rhizobium on host plant biomass production and on the carbon costs of N2 fixation in pea root nodules was studied. Nine strains of Rhizobium leguminosarum were constructed, each containing one of three symbiotic plasmids in combination with one of three different ...

The Host Plant Metabolite Glucose Is the Precursor of Diffusible Signal Factor (DSF) Family Signals in Xanthomonas campestris

OpenAIRE

Deng, Yinyue; Liu, Xiaoling; Wu, Ji'en; Lee, Jasmine; Chen, Shaohua; Cheng, Yingying; Zhang, Chunyan; Zhang, Lian-Hui

2015-01-01

Plant pathogen Xanthomonas campestris pv. campestris produces cis-11-methyl-2-dodecenoic acid (diffusible signal factor [DSF]) as a cell-cell communication signal to regulate biofilm dispersal and virulence factor production. Previous studies have demonstrated that DSF biosynthesis is dependent on the presence of RpfF, an enoyl-coenzyme A (CoA) hydratase, but the DSF synthetic mechanism and the influence of the host plant on DSF biosynthesis are still not clear. We show here that exogenous ad...

Immunization with influenza virus hemagglutinin globular region containing the receptor-binding pocket.

Science.gov (United States)

Jeon, Sung Ho; Arnon, Ruth

2002-01-01

The globular region of hemagglutinin (residues 91-261) membrane glycoprotein of influenza virus that encompasses the binding zone to the oligosaccharide receptor of target cells has been cloned by reverse transcriptase-polymerase chain reaction (RT-PCR). This protein segment (denoted HA91-261 peptide) induced significant immune response in mice. The serum antibodies and lung homogenates from the immunized mice cross-reacted with native virus particles. The cellular immunity was manifested by proliferative splenocyte responses and cytokine release indicating T helper type 1 activity. The plasmid DNA containing this segment (denoted pHA91-261) provoked, in addition, a significant cytotoxic T lymphocyte (CTL) response, whereas the HA91-261 protein fragment led to no such response. Both the DNA and the protein fragment of HA91-261 induced significant protection against viral challenge, although the immune response they induce might be along different pathways. Interestingly, the combined DNA priming-protein boosting immunization regimen did not induce protection against viral challenges even though it led to significant humoral immune responses similar to that induced by the peptide vaccine.

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 (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.

Yeast expressed recombinant Hemagglutinin protein of Novel H1N1 elicits neutralising antibodies in rabbits and mice

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Athmaram TN

2011-11-01

Full Text Available Abstract Currently available vaccines for the pandemic Influenza A (H1N1 2009 produced in chicken eggs have serious impediments viz limited availability, risk of allergic reactions and the possible selection of sub-populations differing from the naturally occurring virus, whereas the cell culture derived vaccines are time consuming and may not meet the demands of rapid global vaccination required to combat the present/future pandemic. Hemagglutinin (HA based subunit vaccine for H1N1 requires the HA protein in glycosylated form, which is impossible with the commonly used bacterial expression platform. Additionally, bacterial derived protein requires extensive purification and refolding steps for vaccine applications. For these reasons an alternative heterologous system for rapid, easy and economical production of Hemagglutinin protein in its glycosylated form is required. The HA gene of novel H1N1 A/California/04/2009 was engineered for expression in Pichia pastoris as a soluble secreted protein. The full length HA- synthetic gene having α-secretory tag was integrated into P. pastoris genome through homologous recombination. The resultant Pichia clones having multiple copy integrants of the transgene expressed full length HA protein in the culture supernatant. The Recombinant yeast derived H1N1 HA protein elicited neutralising antibodies both in mice and rabbits. The sera from immunised animals also exhibited Hemagglutination Inhibition (HI activity. Considering the safety, reliability and also economic potential of Pichia expression platform, our preliminary data indicates the feasibility of using this system as an alternative for large-scale production of recombinant influenza HA protein in the face of influenza pandemic threat.

Effects of plant density on recombinant hemagglutinin yields in an Agrobacterium-mediated transient gene expression system using Nicotiana benthamiana plants.

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Fujiuchi, Naomichi; Matsuda, Ryo; Matoba, Nobuyuki; Fujiwara, Kazuhiro

2017-08-01

Agrobacterium-mediated transient expression systems enable plants to rapidly produce a wide range of recombinant proteins. To achieve economically feasible upstream production and downstream processing, it is beneficial to obtain high levels of two yield-related quantities of upstream production: recombinant protein content per fresh mass of harvested biomass (g gFM -1 ) and recombinant protein productivity per unit area-time (g m -2 /month). Here, we report that the density of Nicotiana benthamiana plants during upstream production had significant impacts on the yield-related quantities of recombinant hemagglutinin (HA). The two quantities were smaller at a high plant density of 400 plants m -2 than at a low plant density of 100 plants m -2 . The smaller quantities at the high plant density were attributed to: (i) a lower HA content in young leaves, which usually have high HA accumulation potentials; (ii) a lower biomass allocation to the young leaves; and (iii) a high area-time requirement for plants. Thus, plant density is a key factor for improving upstream production in Agrobacterium-mediated transient expression systems. Biotechnol. Bioeng. 2017;114: 1762-1770. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The Length of N-Glycans of Recombinant H5N1 Hemagglutinin Influences the Oligomerization and Immunogenicity of Vaccine Antigen

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Edyta Kopera

2017-04-01

Full Text Available Hemagglutinin glycoprotein (HA is a principle influenza vaccine antigen. Recombinant HA-based vaccines become a potential alternative for traditional approach. Complexity and variation of HA N-glycosylation are considered as the important factors for the vaccine design. The number and location of glycan moieties in the HA molecule are also crucial. Therefore, we decided to study the effect of N-glycosylation pattern on the H5 antigen structure and its ability to induce immunological response. We also decided to change neither the number nor the position of the HA glycosylation sites but only the glycan length. Two variants of the H5 antigen with high mannose glycosylation (H5hm and with low-mannose glycosylation (H5Man5 were prepared utilizing different Pichia strains. Our structural studies demonstrated that only the highly glycosylated H5 antigen formed high molecular weight oligomers similar to viral particles. Further, the H5hm was much more immunogenic for mice than H5Man5. In summary, our results suggest that high mannose glycosylation of vaccine antigen is superior to the low glycosylation pattern. Our findings have strong implications for the recombinant HA-based influenza vaccine design.

A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

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Boonsathorn, Naphatsawan; Panthong, Sumolrat; Koksunan, Sarawut; Chittaganpitch, Malinee; Phuygun, Siripaporn; Waicharoen, Sunthareeya; Prachasupap, Apichai; Sasaki, Tadahiro; Kubota-Koketsu, Ritsuko; Yasugi, Mayo; Ono, Ken-ichiro; Arai, Yasuha

2014-01-01

Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses

A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

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Boonsathorn, Naphatsawan; Panthong, Sumolrat [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Koksunan, Sarawut [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Chittaganpitch, Malinee; Phuygun, Siripaporn; Waicharoen, Sunthareeya [National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Prachasupap, Apichai [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Sasaki, Tadahiro [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); Yasugi, Mayo [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); Ono, Ken-ichiro [Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano (Japan); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Arai, Yasuha [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); and others

2014-09-26

Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

Chlamydia infection across host species boundaries promotes distinct sets of transcribed anti-apoptotic factors.

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Joshua eMessinger

2015-12-01

Full Text Available Chlamydiae, obligate intracellular bacteria, cause significant human and veterinary associated diseases. Having emerged an estimated 700-million years ago, these bacteria have twice adapted to humans as a host species, causing sexually transmitted infection (C. trachomatis and respiratory associated disease (C. pneumoniae. The principle mechanism of host cell defense against these intracellular bacteria is the induction of cell death via apoptosis. However, in the arms race of co-evolution, Chlamydiae have developed mechanisms to promote cell viability and inhibit cell death. Herein we examine the impact of Chlamydiae infection across multiple host species on transcription of anti-apoptotic genes. We found mostly distinct patterns of gene expression (Mcl1 and cIAPs elicited by each pathogen-host pair indicating Chlamydiae infection across host species boundaries does not induce a universally shared host response. Understanding species specific host-pathogen interactions is paramount to deciphering how potential pathogens become emerging diseases.

Host age modulates within-host parasite competition.

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

2015-05-01

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 were more susceptible to infection and suffered higher mortality than singly-exposed hosts. Hosts oldest at exposure were least often infected and vice versa. Furthermore, we found that in young multiply-exposed hosts competition was weak, allowing coexistence and transmission of both parasite clones, whereas in older multiply-exposed hosts competitive exclusion was observed. Thus, age-dependent parasite exposure and host demography (age structure) could together play an important role in mediating parasite evolution. At the individual level, our results demonstrate a previously unnoticed interaction of the host's immune system with host age, suggesting that the specificity of immune function changes as hosts mature. Therefore, evolutionary models of parasite virulence might benefit from incorporating age-dependent epidemiological parameters. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Genetic Factors and Host Traits Predict Spore Morphology for a Butterfly Pathogen

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Jacobus C. de Roode

2013-08-01

Full Text Available Monarch butterflies (Danaus plexippus throughout the world are commonly infected by the specialist pathogen Ophryocystis elektroscirrha (OE. This protozoan is transmitted when larvae ingest infectious stages (spores scattered onto host plant leaves by infected adults. Parasites replicate internally during larval and pupal stages, and adult monarchs emerge covered with millions of dormant spores on the outsides of their bodies. Across multiple monarch populations, OE varies in prevalence and virulence. Here, we examined geographic and genetic variation in OE spore morphology using clonal parasite lineages derived from each of four host populations (eastern and western North America, South Florida and Hawaii. Spores were harvested from experimentally inoculated, captive-reared adult monarchs. Using light microscopy and digital image analysis, we measured the size, shape and color of 30 replicate spores per host. Analyses examined predictors of spore morphology, including parasite source population and clone, parasite load, and the following host traits: family line, sex, wing area, and wing color (orange and black pigmentation. Results showed significant differences in spore size and shape among parasite clones, suggesting genetic determinants of morphological variation. Spore size also increased with monarch wing size, and monarchs with larger and darker orange wings tended to have darker colored spores, consistent with the idea that parasite development depends on variation in host quality and resources. We found no evidence for effects of source population on variation in spore morphology. Collectively, these results provide support for heritable variation in spore morphology and a role for host traits in affecting parasite development.

The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

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de Chassey, Benoît; Aublin-Gex, Anne; Ruggieri, Alessia; Meyniel-Schicklin, Laurène; Pradezynski, Fabrine; Davoust, Nathalie; Chantier, Thibault; Tafforeau, Lionel; Mangeot, Philippe-Emmanuel; Ciancia, Claire; Perrin-Cocon, Laure; Bartenschlager, Ralf; André, Patrice; Lotteau, Vincent

2013-01-01

Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

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Benoît de Chassey

Full Text Available Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1 appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.

Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.

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Pila, Emmanuel A; Gordy, Michelle A; Phillips, Valerie K; Kabore, Alethe L; Rudko, Sydney P; Hanington, Patrick C

2016-05-10

Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection.

Host-Plant Specialization Mediates the Influence of Plant Abundance on Host Use by Flower Head-Feeding Insects.

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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.

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

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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

Bystander Host Cell Killing Effects of Clostridium perfringens Enterotoxin

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Archana Shrestha

2016-12-01

Full Text Available Clostridium perfringens enterotoxin (CPE binds to claudin receptors, e.g., claudin-4, and then forms a pore that triggers cell death. Pure cultures of host cells that do not express claudin receptors, e.g., fibroblasts, are unaffected by pathophysiologically relevant CPE concentrations in vitro. However, both CPE-insensitive and CPE-sensitive host cells are present in vivo. Therefore, this study tested whether CPE treatment might affect fibroblasts when cocultured with CPE-sensitive claudin-4 fibroblast transfectants or Caco-2 cells. Under these conditions, immunofluorescence microscopy detected increased death of fibroblasts. This cytotoxic effect involved release of a toxic factor from the dying CPE-sensitive cells, since it could be reproduced using culture supernatants from CPE-treated sensitive cells. Supernatants from CPE-treated sensitive cells, particularly Caco-2 cells, were found to contain high levels of membrane vesicles, often containing a CPE species. However, most cytotoxic activity remained in those supernatants even after membrane vesicle depletion, and CPE was not detected in fibroblasts treated with supernatants from CPE-treated sensitive cells. Instead, characterization studies suggest that a major cytotoxic factor present in supernatants from CPE-treated sensitive cells may be a 10- to 30-kDa host serine protease or require the action of that host serine protease. Induction of caspase-3-mediated apoptosis was found to be important for triggering release of the cytotoxic factor(s from CPE-treated sensitive host cells. Furthermore, the cytotoxic factor(s in these supernatants was shown to induce a caspase-3-mediated killing of fibroblasts. This bystander killing effect due to release of cytotoxic factors from CPE-treated sensitive cells could contribute to CPE-mediated disease.

Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein.

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Yuan, Ping; Leser, George P; Demeler, Borries; Lamb, Robert A; Jardetzky, Theodore S

2008-09-01

The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high alpha-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.

Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

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Beatriz M. A. Fontoura

2013-07-01

Full Text Available Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses.

Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

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Kuss, Sharon K.; Mata, Miguel A.; Zhang, Liang; Fontoura, Beatriz M. A.

2013-01-01

Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses. PMID:23872491

Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding.

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Henry Memczak

Full Text Available Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.

PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease.

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Ray, Tanusree; Pal, Amit

2016-05-01

Bacterial toxins have emerged as promising agents in cancer treatment strategy. Hemagglutinin (HAP) protease secreted by Vibrio cholerae induced apoptosis in breast cancer cells and regresses tumor growth in mice model. The success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity for normal tissues. Increased expression of Protease Activated Receptor-1 (PAR-1) has been reported in different malignant cells. In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50-p65 and the phosphorylation of p38 which triggered the activation of NFκB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same environment makes it a good therapeutic agent for treatment of cancer.

Development and characterization of neutralizing monoclonal antibodies against canine distemper virus hemagglutinin protein.

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Bi, Zhenwei; Xia, Xingxia; Wang, Yongshan; Mei, Yongjie

2015-04-01

Canine distemper virus (CDV) causes a serious multisystemic disease in dogs and other carnivora. Hemagglutinin (H) protein-specific antibodies are mainly responsible for protective immunity against CDV infection. In the present study, six neutralizing MAbs to the H protein of CDV were newly obtained and characterized by immunizing BALB/c mice with a recent Chinese field isolate. Competitive binding inhibition assay revealed that they recognized four distinct antigenic regions of the H protein. Immunofluorescence assay and western blotting showed that all MAbs recognize the conformational rather than the linear epitopes of the H protein. Furthermore, in immunofluorescence and virus neutralization assays, two of the MAbs were found to react only with the recent Chinese field isolate and not with older CDV strains, including vaccine strain Onderstepoort, indicating there are neutralization-related antigenic variations between the recent Chinese field isolate and the older CDV strains examined in this study. The newly established MAbs are useful for differentiating the expanding CDV strains and could be used in immunotherapy and immunodiagnosis against infection with CDV. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

Stochastic acidification, activation of hemagglutinin and escape of influenza viruses from an endosome

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Lagache, Thibault; Sieben, Christian; Meyer, Tim; Herrmann, Andreas; Holcman, David

2017-06-01

Influenza viruses enter the cell inside an endosome. During the endosomal journey, acidification triggers a conformational change of the virus spike protein hemagglutinin (HA) that results in escape of the viral genome from the endosome into the cytoplasm. It is still unclear how the interplay between acidification and HA conformation changes affects the kinetics of the viral endosomal escape. We develop here a stochastic model to estimate the change of conformation of HAs inside the endosome nanodomain. Using a Markov process, we model the arrival of protons to HA binding sites and compute the kinetics of their accumulation. We compute the Mean First Passage Time (MFPT) of the number of HA bound sites to a threshold, which is used to estimate the HA activation rate for a given pH concentration. The present analysis reveals that HA proton binding sites possess a high chemical barrier, ensuring a stability of the spike protein at sub-acidic pH. We predict that activating more than 3 adjacent HAs is necessary to trigger endosomal fusion and this configuration prevents premature release of viruses from early endosomes

Application of recombinant hemagglutinin proteins as alternative antigen standards for pandemic influenza vaccines.

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Choi, Yejin; Kwon, Seong Yi; Oh, Ho Jung; Shim, Sunbo; Chang, Seokkee; Chung, Hye Joo; Kim, Do Keun; Park, Younsang; Lee, Younghee

2017-09-01

The single radial immunodiffusion (SRID) assay, used to quantify hemagglutinin (HA) in influenza vaccines, requires reference reagents; however, because centralized production of reference reagents may slow the emergency deployment of vaccines, alternatives are needed. We investigated the production of HA proteins using recombinant DNA technology, rather than a traditional egg-based production process. The HA proteins were then used in an SRID assay as a reference antigen. We found that HA can be quantified in both egg-based and cell-based influenza vaccines when recombinant HAs (rHAs) are used as the reference antigen. Furthermore, we confirmed that rHAs obtained from strains with pandemic potential, such as H5N1, H7N3, H7N9, and H9N2 strains, can be utilized in the SRID assay. The rHA production process takes just one month, in contrast to the traditional process that takes three to four months. The use of rHAs may reduce the time required to produce reference reagents and facilitate timely introduction of vaccines during emergencies.

Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.

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Eric Baranowski

Full Text Available Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i the development of a specific antibody response and (ii dynamic changes in expression of M. agalactiae surface variable proteins (Vpma, with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.

Spatial and Temporal Epidemiology of Nephropathia Epidemica Incidence and Hantavirus Seroprevalence in Rodent Hosts: Identification of the Main Environmental Factors in Europe.

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Monchatre-Leroy, E; Crespin, L; Boué, F; Marianneau, P; Calavas, D; Hénaux, V

2017-08-01

In Europe, the increasing number of nephropathia epidemica (NE) infections in humans, caused by Puumala virus carried by bank voles (Myodes glareolus), has triggered studies of environmental factors driving these infections. NE infections have been shown to occur in specific geographical areas characterized by environmental factors that influence the distribution and dynamics of host populations and virus persistence in the soil. Here, we review the influence of environmental conditions (including climate factors, food availability and habitat conditions) with respect to incidence in humans and seroprevalence in rodents, considering both direct and indirect transmission pathways. For each type of environmental factor, results and discrepancies between studies are presented and examined in the light of biological hypotheses. Overall, food availability and temperature appear to be the main drivers of host seroprevalence and NE incidence, but data quality and statistical approaches varied greatly among studies. We highlight the issues that now need to be addressed and suggest improvements for study design in regard to the current knowledge on hantavirus epidemiology. © 2016 Blackwell Verlag GmbH.

The predictability of phytophagous insect communities: host specialists as habitat specialists.

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Jörg Müller

Full Text Available The difficulties specialized phytophagous insects face in finding habitats with an appropriate host should constrain their dispersal. Within the concept of metacommunities, this leads to the prediction that host-plant specialists should sort into local assemblages according to the local environmental conditions, i.e. habitat conditions, whereas assemblages of host-plant generalists should depend also on regional processes. Our study aimed at ranking the importance of local environmental factors and species composition of the vegetation for predicting the species composition of phytophagous moth assemblages with either a narrow or a broad host range. Our database consists of 351,506 specimens representing 820 species of nocturnal Macrolepidoptera sampled between 1980 and 2006 using light traps in 96 strict forest reserves in southern Germany. Species were grouped as specialists or generalists according to the food plants of the larvae; specialists use host plants belonging to one genus. We used predictive canonical correspondence and co-correspondence analyses to rank the importance of local environmental factors, the species composition of the vegetation and the role of host plants for predicting the species composition of host-plant specialists and generalists. The cross-validatory fit for predicting the species composition of phytophagous moths was higher for host-plant specialists than for host-plant generalists using environmental factors as well as the composition of the vegetation. As expected for host-plant specialists, the species composition of the vegetation was a better predictor of the composition of these assemblages than the environmental variables. But surprisingly, this difference for specialized insects was not due to the occurrence of their host plants. Overall, our study supports the idea that owing to evolutionary constraints in finding a host, host-plant specialists and host-plant generalists follow two different models of

HostPhinder: A Phage Host Prediction Tool

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Julia Villarroel

2016-05-01

Full Text Available The current dramatic increase of antibiotic resistant bacteria has revitalised the interest in bacteriophages as alternative antibacterial treatment. Meanwhile, the development of bioinformatics methods for analysing genomic data places high-throughput approaches for phage characterization within reach. Here, we present HostPhinder, a tool aimed at predicting the bacterial host of phages by examining the phage genome sequence. Using a reference database of 2196 phages with known hosts, HostPhinder predicts the host species of a query phage as the host of the most genomically similar reference phages. As a measure of genomic similarity the number of co-occurring k-mers (DNA sequences of length k is used. Using an independent evaluation set, HostPhinder was able to correctly predict host genus and species for 81% and 74% of the phages respectively, giving predictions for more phages than BLAST 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 bacterial hosts. HostPhinder is available as an interactive web service [1] and as a stand alone download from the Docker registry [2].

Simultaneous Identification of Potential Pathogenicity Factors of Mycoplasma agalactiae in the Natural Ovine Host by Negative Selection

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Hegde, Shivanand; Hegde, Shrilakshmi; Zimmermann, Martina; Flöck, Martina; Spergser, Joachim; Rosengarten, Renate; Chopra-Dewasthaly, Rohini

2015-01-01

Mycoplasmas possess complex pathogenicity determinants that are largely unknown at the molecular level. Mycoplasma agalactiae serves as a useful model to study the molecular basis of mycoplasma pathogenicity. The generation and in vivo screening of a transposon mutant library of M. agalactiae were employed to unravel its host colonization factors. Tn4001mod mutants were sequenced using a novel sequencing method, and functionally heterogeneous pools containing 15 to 19 selected mutants were sc...

Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin

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Hauck, Nastasja C.; Kirpach, Josiane; Kiefer, Christina; Farinelle, Sophie; Morris, Stephen A.; Muller, Claude P.; Lu, I-Na

2018-01-01

To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH). Our vaccine targeting LAH of hemagglutinin elicited significant seroconversion and protection against homologous and heterologous influenza virus strains in mice. The vaccine not only significantly reduced lung viral titers, but also induced a well-known bottleneck effect by decreasing virus diversity. In contrast to the classical bottleneck effect, here we showed a significant increase in the frequency of viruses with amino acid sequences identical to that of vaccine targeting LAH domain. No escape mutant emerged after vaccination. These results not only support the potential of a universal influenza vaccine targeting the conserved LAH domains, but also clearly demonstrate that the well-established bottleneck effect on viral quasispecies evolution does not necessarily generate escape mutants. PMID:29587397

Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin

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Nastasja C. Hauck

2018-03-01

Full Text Available To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA long alpha helix (LAH. Our vaccine targeting LAH of hemagglutinin elicited significant seroconversion and protection against homologous and heterologous influenza virus strains in mice. The vaccine not only significantly reduced lung viral titers, but also induced a well-known bottleneck effect by decreasing virus diversity. In contrast to the classical bottleneck effect, here we showed a significant increase in the frequency of viruses with amino acid sequences identical to that of vaccine targeting LAH domain. No escape mutant emerged after vaccination. These results not only support the potential of a universal influenza vaccine targeting the conserved LAH domains, but also clearly demonstrate that the well-established bottleneck effect on viral quasispecies evolution does not necessarily generate escape mutants.

No Major Host Genetic Risk Factor Contributed to A(H1N12009 Influenza Severity.

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Koldo Garcia-Etxebarria

Full Text Available While most patients affected by the influenza A(H1N1 pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

The role of filamentous hemagglutinin adhesin in adherence and biofilm formation in Acinetobacter baumannii ATCC19606(T).

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Darvish Alipour Astaneh, Shakiba; Rasooli, Iraj; Mousavi Gargari, Seyed Latif

2014-09-01

Filamentous hemagglutinin adhesins (FHA) are key factors for bacterial attachment and subsequent cell accumulation on substrates. Here an FHA-like Outer membrane (OM) adhesin of Acinetobacter baumannii ATCC19606(T) was displayed on Escherichia coli. The candidate autotransporter (AT) genes were identified in A. baumannii ATCC19606(T) genome. The exoprotein (FhaB1) and transporter (FhaC1) were produced independently within the same cell (FhaB1C1). The fhaC1 was mutated. In vitro adherence to epithelial cells of the recombinant FhaB1C1 and the mutant strains were compared with A. baumanni ATCC19606(T). A bivalent chimeric protein (K) composed of immunologically important portions of fhaB1 (B) and fhaC1 (C) was constructed. The mice vaccinated with chimeric protein were challenged with A. baumannii ATCC19606(T) and FhaB1C1 producing recombinant E. coli. Mutations in the fhaC1 resulted in the absence of FhaB1 in the OM. Expression of FhaB1C1 enhanced the adherence of recombinant bacteria to A546 bronchial cell line. The results revealed association of FhaB1 with bacterial adhesion and biofilm formation. Immunization with a combination of recombinant B and K proteins proved protective against A. baumanni ATCC19606(T). The findings may be applied in active and passive immunization strategies against A. baumannii. Copyright © 2014 Elsevier Ltd. All rights reserved.

Host genetic risk factors for West Nile virus infection and disease progression.

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Abigail W Bigham

Full Text Available West Nile virus (WNV, a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035 and MX1, (OR 0.19, p = 0.014 were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003 was associated with increased risk for West Nile encephalitis and paralysis (WNE/P. Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

Characterization of a diffusible signaling factor from Xylella fastidiosa.

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Beaulieu, Ellen D; Ionescu, Michael; Chatterjee, Subhadeep; Yokota, Kenji; Trauner, Dirk; Lindow, Steven

2013-01-08

Cell-cell signaling in Xylella fastidiosa has been implicated in the coordination of traits enabling colonization in plant hosts as well as insect vectors. This cell density-dependent signaling has been attributed to a diffusible signaling factor (DSF) produced by the DSF synthase RpfF. DSF produced by related bacterial species are unsaturated fatty acids, but that of X. fastidiosa was thought to be different from those of other taxa. We describe here the isolation and characterization of an X. fastidiosa DSF (XfDSF) as 2(Z)-tetradecenoic acid. This compound was isolated both from recombinant Erwinia herbicola expressing X. fastidiosa rpfF and from an X. fastidiosa rpfC deletion mutant that overproduces DSF. Since an rpfF mutant is impaired in biofilm formation and underexpresses the hemagglutinin-like protein-encoding genes hxfA and hxfB, we demonstrate that these traits can be restored by ca. 0.5 µM XfDSF but not by myristic acid, the fully saturated tetradecenoic acid. A phoA-based X. fastidiosa biosensor that assesses DSF-dependent expression of hxfA or hxfB revealed a high level of molecular specificity of DSF signaling. X. fastidiosa causes diseases in many important plants, including grape, where it incites Pierce's disease. Virulence of X. fastidiosa for grape is coordinated by cell-cell signaling molecules, designated DSF (Diffusible Signaling Factor). Mutants blocked in DSF production are hypervirulent for grape, suggesting that virulence is suppressed upon DSF accumulation and that disease could be controlled by artificial elevation of the DSF level in plants. In this work, we describe the isolation of the DSF produced by X. fastidiosa and the verification of its biological activity as an antivirulence factor. We also have developed X. fastidiosa DSF biosensors to evaluate the specificity of cell-cell signaling to be investigated.

Novel Burkholderia mallei Virulence Factors Linked to Specific Host-Pathogen Protein Interactions

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2013-06-23

equine hosts. Thus, the genes retained in B. mallei share a high sequence similarity to genes common to B. pseudomallei (3), and many virulence...oppor- tunistic infections in mammalian hosts. Even for the equine - adapted and, thus, more genetically constrained, B. mallei pathogen, we cannot...BioDrugs: Clin. Immunotherapeut., Biopharmaceut. Gene Therapy 17, 413–424 88. Anderson, D. M., and Frank, D. W. (2012) Five mechanisms of manipula

HSPA5 is an essential host factor for Ebola virus infection.

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Reid, St Patrick; Shurtleff, Amy C; Costantino, Julie A; Tritsch, Sarah R; Retterer, Cary; Spurgers, Kevin B; Bavari, Sina

2014-09-01

Development of novel strategies targeting the highly virulent ebolaviruses is urgently required. A proteomic study identified the ER chaperone HSPA5 as an ebolavirus-associated host protein. Here, we show using the HSPA5 inhibitor (-)- epigallocatechin gallate (EGCG) that the chaperone is essential for virus infection, thereby demonstrating a functional significance for the association. Furthermore, in vitro and in vivo gene targeting impaired viral replication and protected animals in a lethal infection model. These findings demonstrate that HSPA5 is vital for replication and can serve as a viable target for the design of host-based countermeasures. Published by Elsevier B.V.

Host selection by the shiny cowbird

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Wiley, J.W.

1988-01-01

Factors important in Shiny Cowbird (Molothrus bonariensis) host selection were examined within the mangrove community in Puerto Rico. Cowbirds did not parasitize birds in proportion to their abundance. The cowbird breeding season coincided with those of its major hosts, which were 'high-quality' foster species (i.e., species that fledge .gtoreq. 55% of cowbirds hatched: Yellow Warbler, Dendroica petechia; Yellow-shouldered Blackbird, Agelaius xanthomus; Black-whiskered Vireo, Vireo altiloquus; Black-cowled Oriole, Icterus dominicensis; Peurto Rican Flycatcher, Myiarchus antillarum; Troupial, Icterus icterus), and did not extend into other periods even though nests of 'low-quality: species (i.e., species that fledge < 55% of cowbird chicks that hatched: Bronze Mannikin, Lonchura cucullata; Greater Antillean Grackle, Quiscalus niger; Gray Kingbird, Tyrannus dominicensis; Northern Mockingbird, Mimus polyglottos; Red-legged Thrush, Turdus plumbeus) were available. Shiny Cowbird food habits and egg size were similar to those of their hosts, suggesting that cowbirds choose hosts partly on the basis of this combination. Cowbirds located host nests primarily by cryptically watching activities of birds in likely habitats. Other nest locating strategies were active searching of suitable habitat and 'flushing' of hosts by the cowbird's noisy approach. Cowbirds closely monitored nest status with frequent visits that peaked on the host's first day of egg laying. Hosts using covered nests (e.g., cavities, domed nests) were as vulnerable to cowbird parasitism as those building open nests.

Dual RNA-sequencing of Eucalyptus nitens during Phytophthora cinnamomi challenge reveals pathogen and host factors influencing compatibility

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Febe Elizabeth Meyer

2016-03-01

Full Text Available Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1. Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction.

The influence of "host release factor" on carbon release by zooxanthellae isolated from fed and starved Aiptasia pallida (Verrill).

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Davy, S K; Cook, C B

2001-06-01

Symbiotic dinoflagellates (zooxanthellae) typically respond to extracts of host tissue with enhanced release of short-term photosynthetic products. We examined this "host release factor" (HRF) response using freshly isolated zooxanthellae of differing nutritional status. The nutritional status was manipulated by either feeding or starving the sea anemone Aiptasia pallida (Verrill). The release of fixed carbon from isolated zooxanthellae was measured using 14C in 30 min experiments. Zooxanthellae in filtered seawater alone released approximately 5% of photosynthate irrespective of host feeding history. When we used a 10-kDa ultrafiltrate of A. pallida host tissue as a source of HRF, approximately 14% of photosynthate was released to the medium. This increased to over 25% for zooxanthellae from anemones starved for 29 days or more. The cell-specific photosynthetic rate declined with starvation in these filtrate experiments, but the decline was offset by the increased percentage release. Indeed, the total amount of released photosynthate remained unchanged, or even increased, as zooxanthellae became more nutrient deficient. Similar trends were also observed when zooxanthellae from A. pallida were incubated in a 3-kDa ultrafiltrate of the coral Montastraea annularis, suggesting that HRF in the different filtrates operated in a similar manner. Our results support the suggestion that HRF diverts surplus carbon away from storage compounds to translocated compounds such as glycerol.

Large-scale FMO-MP3 calculations on the surface proteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA)

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Mochizuki, Yuji; Yamashita, Katsumi; Fukuzawa, Kaori; Takematsu, Kazutomo; Watanabe, Hirofumi; Taguchi, Naoki; Okiyama, Yoshio; Tsuboi, Misako; Nakano, Tatsuya; Tanaka, Shigenori

2010-06-01

Two proteins on the influenza virus surface have been well known. One is hemagglutinin (HA) associated with the infection to cells. The fragment molecular orbital (FMO) calculations were performed on a complex consisting of HA trimer and two Fab-fragments at the third-order Møller-Plesset perturbation (MP3) level. The numbers of residues and 6-31G basis functions were 2351 and 201276, and thus a massively parallel-vector computer was utilized to accelerate the processing. This FMO-MP3 job was completed in 5.8 h with 1024 processors. Another protein is neuraminidase (NA) involved in the escape from infected cells. The FMO-MP3 calculation was also applied to analyze the interactions between oseltamivir and surrounding residues in pharmacophore.

Host plant adaptation in Drosophila mettleri populations.

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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.

Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

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Kim, Ye-Ram; Yang, Chul-Su

2017-09-28

Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

Highlights Regarding Host Predisposing Factors to Recurrent Vulvovaginal Candidiasis: Chronic Stress and Reduced Antioxidant Capacity.

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Akimoto-Gunther, Luciene; Bonfim-Mendonça, Patrícia de Souza; Takahachi, Gisele; Irie, Mary Mayumi T; Miyamoto, Sônia; Consolaro, Márcia Edilaine Lopes; Svidzinsk, Terezinha I Estivalet

2016-01-01

We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC), including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI). Yeasts were isolated from 71 (26%) women: 23 (32.4%) with a positive culture but without symptoms (COL), 22 (31%) in an acute episode (VVC), and 26 (36.6%) with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture) comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC) than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels) and reduced antioxidant capacity can be host predisposing factors to RVVC.

Highlights Regarding Host Predisposing Factors to Recurrent Vulvovaginal Candidiasis: Chronic Stress and Reduced Antioxidant Capacity.

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Luciene Akimoto-Gunther

Full Text Available We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC, including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI. Yeasts were isolated from 71 (26% women: 23 (32.4% with a positive culture but without symptoms (COL, 22 (31% in an acute episode (VVC, and 26 (36.6% with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels and reduced antioxidant capacity can be host predisposing factors to RVVC.

A loss of function analysis of host factors influencing Vaccinia virus replication by RNA interference.

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Philippa M Beard

Full Text Available Vaccinia virus (VACV is a large, cytoplasmic, double-stranded DNA virus that requires complex interactions with host proteins in order to replicate. To explore these interactions a functional high throughput small interfering RNA (siRNA screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated a low multiplicity of infection, thereby enhancing detection of cellular proteins involved in cell-to-cell spread of VACV. The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV replication. These HFs were investigated further by comparisons with transcriptional profiling data sets and HFs identified in RNAi screens of other viruses. In addition, functional and pathway analysis of the entire screen was carried out to highlight cellular mechanisms involved in VACV replication. This revealed, as anticipated, that many pro-viral HFs are involved in translation of mRNA and, unexpectedly, suggested that a range of proteins involved in cellular transcriptional processes and several DNA repair pathways possess anti-viral activity. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. This advancement in our understanding of the VACV life cycle provides a reliable knowledge base for the improvement of poxvirus-based vaccine vectors and development of anti-viral theraputics.

Tipping the balance: Sclerotinia sclerotiorum secreted oxalic acid suppresses host defenses by manipulating the host redox environment.

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Brett Williams

2011-06-01

Full Text Available Sclerotinia sclerotiorum is a necrotrophic ascomycete fungus with an extremely broad host range. This pathogen produces the non-specific phytotoxin and key pathogenicity factor, oxalic acid (OA. Our recent work indicated that this fungus and more specifically OA, can induce apoptotic-like programmed cell death (PCD in plant hosts, this induction of PCD and disease requires generation of reactive oxygen species (ROS in the host, a process triggered by fungal secreted OA. Conversely, during the initial stages of infection, OA also dampens the plant oxidative burst, an early host response generally associated with plant defense. This scenario presents a challenge regarding the mechanistic details of OA function; as OA both suppresses and induces host ROS during the compatible interaction. In the present study we generated transgenic plants expressing a redox-regulated GFP reporter. Results show that initially, Sclerotinia (via OA generates a reducing environment in host cells that suppress host defense responses including the oxidative burst and callose deposition, akin to compatible biotrophic pathogens. Once infection is established however, this necrotroph induces the generation of plant ROS leading to PCD of host tissue, the result of which is of direct benefit to the pathogen. In contrast, a non-pathogenic OA-deficient mutant failed to alter host redox status. The mutant produced hypersensitive response-like features following host inoculation, including ROS induction, callose formation, restricted growth and cell death. These results indicate active recognition of the mutant and further point to suppression of defenses by the wild type necrotrophic fungus. Chemical reduction of host cells with dithiothreitol (DTT or potassium oxalate (KOA restored the ability of this mutant to cause disease. Thus, Sclerotinia uses a novel strategy involving regulation of host redox status to establish infection. These results address a long-standing issue

Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin.

Science.gov (United States)

Wilson, Jason R; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O; Katz, Jacqueline M; York, Ian A

2014-06-01

We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72-130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help to define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely related viruses. In spite of this limited range of protection, recent findings indicate that individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help to put bounds on the

Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

International Nuclear Information System (INIS)

Zhang, Xinsheng; Wallace, Olivia L.; Domi, Arban; Wright, Kevin J.; Driscoll, Jonathan; Anzala, Omu; Sanders, Eduard J.; Kamali, Anatoli; Karita, Etienne; Allen, Susan; Fast, Pat; Gilmour, Jill; Price, Matt A.; Parks, Christopher L.

2015-01-01

Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance

Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xinsheng, E-mail: xzhang@iavi.org [AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States); Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY (United States); Wallace, Olivia L.; Domi, Arban; Wright, Kevin J.; Driscoll, Jonathan [AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States); Anzala, Omu [Kenya AIDS Vaccine Initiative (KAVI)-Institute of Clinical Research, Nairobi (Kenya); Sanders, Eduard J. [Centre for Geographic Medicine Research, Kenya Medical Research Institute (KEMRI), Kilifi, Kenya & Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Headington (United Kingdom); Kamali, Anatoli [MRC/UVRI Uganda Virus Research Unit on AIDS, Masaka and Entebbe (Uganda); Karita, Etienne [Projet San Francisco, Kigali (Rwanda); Allen, Susan [Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA (United States); Fast, Pat [Department of Medical Affairs, International AIDS Vaccine Initiative, NY, NY (United States); Gilmour, Jill [Human Immunology Laboratory, International AIDS Vaccine Initiative, London (United Kingdom); Price, Matt A. [Department of Medical Affairs, International AIDS Vaccine Initiative, NY, NY (United States); Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA (United States); Parks, Christopher L. [AIDS Vaccine Design and Development Laboratory, International AIDS Vaccine Initiative (IAVI), Brooklyn, NY (United States); Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY (United States)

2015-08-15

Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.

Continental-scale variation in seaweed host-associated bacterial communities is a function of host condition, not geography.

Science.gov (United States)

Marzinelli, Ezequiel M; Campbell, Alexandra H; Zozaya Valdes, Enrique; Vergés, Adriana; Nielsen, Shaun; Wernberg, Thomas; de Bettignies, Thibaut; Bennett, Scott; Caporaso, J Gregory; Thomas, Torsten; Steinberg, Peter D

2015-10-01

Interactions between hosts and associated microbial communities can fundamentally shape the development and ecology of 'holobionts', from humans to marine habitat-forming organisms such as seaweeds. In marine systems, planktonic microbial community structure is mainly driven by geography and related environmental factors, but the large-scale drivers of host-associated microbial communities are largely unknown. Using 16S-rRNA gene sequencing, we characterized 260 seaweed-associated bacterial and archaeal communities on the kelp Ecklonia radiata from three biogeographical provinces spanning 10° of latitude and 35° of longitude across the Australian continent. These phylogenetically and taxonomically diverse communities were more strongly and consistently associated with host condition than geographical location or environmental variables, and a 'core' microbial community characteristic of healthy kelps appears to be lost when hosts become stressed. Microbial communities on stressed individuals were more similar to each other among locations than those on healthy hosts. In contrast to biogeographical patterns of planktonic marine microbial communities, host traits emerge as critical determinants of associated microbial community structure of these holobionts, even at a continental scale. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

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

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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.

Host Ecology Rather Than Host Phylogeny Drives Amphibian Skin Microbial Community Structure in the Biodiversity Hotspot of Madagascar

OpenAIRE

Bletz, Molly C.; Archer, Holly; Harris, Reid N.; McKenzie, Valerie J.; Rabemananjara, Falitiana C. E.; Rakotoarison, Andolalao; Vences, Miguel

2017-01-01

Host-associated microbiotas of vertebrates are diverse and complex communities that contribute to host health. In particular, for amphibians, cutaneous microbial communities likely play a significant role in pathogen defense; however, our ecological understanding of these communities is still in its infancy. Here, we take advantage of the fully endemic and locally species-rich amphibian fauna of Madagascar to investigate the factors structuring amphibian skin microbiota on a large scale. Usin...

Deconstructing host-pathogen interactions in Drosophila

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Ethan Bier

2012-01-01

Full Text Available 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.

Host genetics affect microbial ecosystems via host immunity.

Science.gov (United States)

El Kafsi, Hela; Gorochov, Guy; Larsen, Martin

2016-10-01

Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity. Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics. We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.

Salmonella Typhimurium metabolism affects virulence in the host – A mini-review

DEFF Research Database (Denmark)

Herrero-fresno, Ana; Olsen, John Elmerdhahl

2018-01-01

Salmonella enterica remains an important food borne pathogen in all regions of the world with S. Typhimurium as one of the most frequent serovars causing food borne disease. Since the majority of human cases are caused by food of animal origin, there has been a high interest in understanding how S....... Typhimurium interacts with the animal host, mostly focusing on factors that allow it to breach host barriers and to manipulate host cells to the benefit of itself. Up to recently, such studies have ignored the metabolic factors that allow the bacteria to multiply in the host, but this is changing rapidly...

The case of a city where 1 in 6 residents is a refugee: ecological factors and host community adaptation in successful resettlement.

Science.gov (United States)

Smith, R Scott

2008-12-01

The notable success of an upstate New York community in resettling refugees raises the question of whether multiple waves of resettlement over a 15-year period have resulted in greater accommodation to refugees. Structured interviews based on transactional models of acculturation were used along with archival data to explore ecological factors supporting a host community's behavioral flexibility and perseverance in response to the influx of refugees. Evidence suggests that socioeconomic climate, historical background/social norms, and the organizational structure of agencies involved in resettlement moderate successful inclusion of refugees into a host community in a bidirectional process.

Broadly-Reactive Neutralizing and Non-neutralizing Antibodies Directed against the H7 Influenza Virus Hemagglutinin Reveal Divergent Mechanisms of Protection.

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Gene S Tan

2016-04-01

Full Text Available In the early spring of 2013, Chinese health authorities reported several cases of H7N9 influenza virus infections in humans. Since then the virus has established itself at the human-animal interface in Eastern China and continues to cause several hundred infections annually. In order to characterize the antibody response to the H7N9 virus we generated several mouse monoclonal antibodies against the hemagglutinin of the A/Shanghai/1/13 (H7N9 virus. Of particular note are two monoclonal antibodies, 1B2 and 1H5, that show broad reactivity to divergent H7 hemagglutinins. Monoclonal antibody 1B2 binds to viruses of the Eurasian and North American H7 lineages and monoclonal antibody 1H5 reacts broadly to virus isolates of the Eurasian lineage. Interestingly, 1B2 shows broad hemagglutination inhibiting and neutralizing activity, while 1H5 fails to inhibit hemagglutination and demonstrates no neutralizing activity in vitro. However, both monoclonal antibodies were highly protective in an in vivo passive transfer challenge model in mice, even at low doses. Experiments using mutant antibodies that lack the ability for Fc/Fc-receptor and Fc/complement interactions suggest that the protection provided by mAb 1H5 is, at least in part, mediated by the Fc-fragment of the mAb. These findings highlight that a protective response to a pathogen may not only be due to neutralizing antibodies, but can also be the result of highly efficacious non-neutralizing antibodies not readily detected by classical in vitro neutralization or hemagglutination inhibition assays. This is of interest because H7 influenza virus vaccines induce only low hemagglutination inhibiting antibody titers while eliciting robust antibody titers as measured by ELISA. Our data suggest that these binding but non-neutralizing antibodies contribute to protection in vivo.

No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

Science.gov (United States)

Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

2015-01-01

While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

Adaptation to toxic hosts as a factor in the evolution of insecticide resistance.

Science.gov (United States)

Alyokhin, Andrei; Chen, Yolanda H

2017-06-01

Insecticide resistance is a serious economic problem that jeopardizes sustainability of chemical control of herbivorous insects and related arthropods. It can be viewed as a specific case of adaptation to toxic chemicals, which has been driven in large part, but not exclusively, by the necessity for insect pests to tolerate defensive compounds produced by their host plants. Synthetic insecticides may simply change expression of specific sets of detoxification genes that have evolved due to ancestral associations with host plants. Feeding on host plants with more abundant or novel secondary metabolites has even been shown to prime insect herbivores to tolerate pesticides. Clear understanding of basic evolutionary processes is important for achieving lasting success in managing herbivorous arthropods. Copyright © 2017 Elsevier Inc. All rights reserved.

Host state screening process: Regional management plan: [Final report

International Nuclear Information System (INIS)

Drobny, N.L.

1986-01-01

This report discusses the procedure and cirteria that the Commission selected for designating a host state, should a state not volunteer for this role. Section 2 describes the wide range of approaches considered. Advantages and disadvantages of each are reviewed briefly, and the overall timetable established by the Commission for host state selection is presented. Section 3 describes the selected process for host state designation which involves emphasis on waste quantities generated and transportation factors. Section 4 presents relevant data on characteristics of wastes presently generated and presents estimates for future waste generation to Year 2015. Section 5 presents the results of transportation analyses considering the distance over which waste would be transported and safety (accident) statistics for waste transport routes. Section 6 integrates the conclusions from the analysis of waste volumes generated and transportation factors and suggests how these results might be used to designate a host state. 11 refs., 6 figs., 9 tabs

Host Factors Influencing the Retrohoming Pathway of Group II Intron RmInt1, Which Has an Intron-Encoded Protein Naturally Devoid of Endonuclease Activity.

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Rafael Nisa-Martínez

Full Text Available Bacterial group II introns are self-splicing catalytic RNAs and mobile retroelements that have an open reading frame encoding an intron-encoded protein (IEP with reverse transcriptase (RT and RNA splicing or maturase activity. Some IEPs carry a DNA endonuclease (En domain, which is required to cleave the bottom strand downstream from the intron-insertion site for target DNA-primed reverse transcription (TPRT of the inserted intron RNA. Host factors complete the insertion of the intron. By contrast, the major retrohoming pathway of introns with IEPs naturally lacking endonuclease activity, like the Sinorhizobium meliloti intron RmInt1, is thought to involve insertion of the intron RNA into the template for lagging strand DNA synthesis ahead of the replication fork, with possible use of the nascent strand to prime reverse transcription of the intron RNA. The host factors influencing the retrohoming pathway of such introns have not yet been described. Here, we identify key candidates likely to be involved in early and late steps of RmInt1 retrohoming. Some of these host factors are common to En+ group II intron retrohoming, but some have different functions. Our results also suggest that the retrohoming process of RmInt1 may be less dependent on the intracellular free Mg2+ concentration than those of other group II introns.

Gastrointestinal function in the parasitized host

International Nuclear Information System (INIS)

Castro, G.A.

1981-01-01

Emphasis in this review is on (1) digestive-absorptive, secretory and smooth muscle functions altered by gastrointestinal (GI) parasites, (2) mechanisms by which parasites induce changes, and (3) the influence of parasite-induced alterations on the health of the host. Examples involving laboratory and domestic animals indicate that inflammation is an important factor in pathological alterations in epithelial and smooth muscle tissues throughout the alimentary canal. Observations on GI secretory activity reveal an influence of parasites on the host GI endocrine system. It is argued that assessments of the significance of parasite-induced changes on the host must be balanced with the adaptive potential and 'reserve capacity' of the GI system. In this regard host immunity should be considered a specific adaptation. Some tracer studies are mentioned marginally, such as the use of 14 C polyethylene glycol to estimate the direction of not fluid movement in the small intestine, and the use of 51 Cr to demonstrate the significantly faster intestinal transit in Trichinella spiralis infected animals

Bacterial Serine/Threonine Protein Kinases in Host-Pathogen Interactions*

Science.gov (United States)

Canova, Marc J.; Molle, Virginie

2014-01-01

In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection. PMID:24554701

Bacterial serine/threonine protein kinases in host-pathogen interactions.

Science.gov (United States)

Canova, Marc J; Molle, Virginie

2014-04-04

In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection.

Butterfly Larval Host Plant use in a Tropical Urban Context: Life History Associations, Herbivory, and Landscape Factors

Science.gov (United States)

Tiple, Ashish D.; Khurad, Arun M.; Dennis, Roger L. H.

2011-01-01

This study examines butterfly larval host plants, herbivory and related life history attributes within Nagpur City, India. The larval host plants of 120 butterfly species are identified and their host specificity, life form, biotope, abundance and perennation recorded; of the 126 larval host plants, most are trees (49), with fewer herbs (43), shrubs (22), climbers (7) and stem parasites (2). They include 89 wild, 23 cultivated, 11 wild/cultivated and 3 exotic plant species; 78 are perennials, 43 annuals and 5 biannuals. Plants belonging to Poaceae and Fabaceae are most widely used by butterfly larvae. In addition to distinctions in host plant family affiliation, a number of significant differences between butterfly families have been identified in host use patterns: for life forms, biotopes, landforms, perennation, host specificity, egg batch size and ant associations. These differences arising from the development of a butterfly resource database have important implications for conserving butterfly species within the city area. Differences in overall butterfly population sizes within the city relate mainly to the number of host plants used, but other influences, including egg batch size and host specificity are identified. Much of the variation in population size is unaccounted for and points to the need to investigate larval host plant life history and strategies as population size is not simply dependent on host plant abundance. PMID:21864159

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

2015-02-01

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.

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.

[Photosynthetic characteristics of Cuscuta japonica and its hosts during parasitization and after detachment].

Science.gov (United States)

Wang, Dong; Hu, Fei; Chen, Yu-Fen; Yang, Jun; Kong, Chui-Hua

2007-08-01

The study on the photosynthetic characteristics of Cuscuta japonica and its hosts showed that there was a negative correlation between the photosynthetic pigment content (PPC) of C. japonica and its hosts. The PPC increased in the C. japonica-preferred hosts' parasitized and neighboring leaves, but decreased in its less preferred hosts' parasitized and neighboring leaves. The leaves parasitized by C. japonica and their neighboring far from the parasitized ones had a lowered net photosynthesis rate P(n), and the decreasing order accorded with that of parasitization. The decrease of P(n) for C. japonica-less preferred hosts was mainly due to the stomatal factors, but that for the preferred hosts was regulated by multi-factors. Under light, the PPC of C. japonica detached from preferred hosts increased faster than that of C. japonica detached from less preferred hosts, but the dry matter decrease was in adverse. In dark, however, the changes in PPC and dry matter content of C. japonica were not significant, whatever hosts it was detached from.

Ecological and genetic factors influencing the transition between host-use strategies in sympatric Heliconius butterflies.

Science.gov (United States)

Merrill, R M; Naisbit, R E; Mallet, J; Jiggins, C D

2013-09-01

Shifts in host-plant use by phytophagous insects have played a central role in their diversification. Evolving host-use strategies will reflect a trade-off between selection pressures. The ecological niche of herbivorous insects is partitioned along several dimensions, and if populations remain in contact, recombination will break down associations between relevant loci. As such, genetic architecture can profoundly affect the coordinated divergence of traits and subsequently the ability to exploit novel habitats. The closely related species Heliconius cydno and H. melpomene differ in mimetic colour pattern, habitat and host-plant use. We investigate the selection pressures and genetic basis underlying host-use differences in these two species. Host-plant surveys reveal that H. melpomene specializes on a single species of Passiflora. This is also true for the majority of other Heliconius species in secondary growth forest at our study site, as expected under a model of interspecific competition. In contrast, H. cydno, which uses closed-forest habitats where both Heliconius and Passiflora are less common, appears not to be restricted by competition and uses a broad selection of the available Passiflora. However, other selection pressures are likely involved, and field experiments reveal that early larval survival of both butterfly species is highest on Passiflora menispermifolia, but most markedly so for H. melpomene, the specialist on that host. Finally, we demonstrate an association between host-plant acceptance and colour pattern amongst interspecific hybrids, suggesting that major loci underlying these important ecological traits are physically linked in the genome. Together, our results reveal ecological and genetic associations between shifts in habitat, host use and mimetic colour pattern that have likely facilitated both speciation and coexistence. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

Constraints on host choice: why do parasitic birds rarely exploit some common potential hosts?

Czech Academy of Sciences Publication Activity Database

Grim, T.; Samaš, P.; Moskát, C.; Kleven, O.; Honza, Marcel; Moksnes, A.; Roskaft, E.; Stokke, B. G.

2011-01-01

Roč. 80, č. 3 (2011), s. 508-518 ISSN 0021-8790 R&D Projects: GA AV ČR IAA600930605 Institutional research plan: CEZ:AV0Z60930519 Keywords : antiparasite defence * co-evolution * host selection * interactive effects * parasite avoidance Subject RIV: EG - Zoology Impact factor: 4.937, year: 2011

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

International Nuclear Information System (INIS)

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

2015-01-01

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. (paper)

Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation.

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Koymans, Kirsten J; Vrieling, Manouk; Gorham, Ronald D; van Strijp, Jos A G

2017-01-01

Staphylococcus aureus is a successful human and animal pathogen. Its pathogenicity is linked to its ability to secrete a large amount of virulence factors. These secreted proteins interfere with many critical components of the immune system, both innate and adaptive, and hamper proper immune functioning. In recent years, numerous studies have been conducted in order to understand the molecular mechanism underlying the interaction of evasion molecules with the host immune system. Structural studies have fundamentally contributed to our understanding of the mechanisms of action of the individual factors. Furthermore, such studies revealed one of the most striking characteristics of the secreted immune evasion molecules: their conserved structure. Despite high-sequence variability, most immune evasion molecules belong to a small number of structural categories. Another remarkable characteristic is that S. aureus carries most of these virulence factors on mobile genetic elements (MGE) or ex-MGE in its accessory genome. Coevolution of pathogen and host has resulted in immune evasion molecules with a highly host-specific function and prevalence. In this review, we explore how these shared structures and genomic locations relate to function and host specificity. This is discussed in the context of therapeutic options for these immune evasion molecules in infectious as well as in inflammatory diseases.

Seasonal forcing in a host-macroparasite system.

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Taylor, Rachel A; White, Andrew; Sherratt, Jonathan A

2015-01-21

Seasonal forcing represents a pervasive source of environmental variability in natural systems. Whilst it is reasonably well understood in interacting populations and host-microparasite systems, it has not been studied in detail for host-macroparasite systems. In this paper we analyse the effect of seasonal forcing in a general host-macroparasite system with explicit inclusion of the parasite larval stage and seasonal forcing applied to the birth rate of the host. We emphasise the importance of the period of the limit cycles in the unforced system on the resulting dynamics in the forced system. In particular, when subject to seasonal forcing host-macroparasite systems are capable of multi-year cycles, multiple solution behaviour, quasi-periodicity and chaos. The host-macroparasite systems show a larger potential for multiple solution behaviour and a wider range of periodic solutions compared to similar interacting population and microparasite systems. By examining the system for parameters that represent red grouse and the macroparasite nematode Trichostrongylus tenuis we highlight how seasonality could be an important factor in explaining the wide range of seemingly uncorrelated cycle periods observed in grouse abundance in England and Scotland. Copyright © 2014 Elsevier Ltd. All rights reserved.

Transmission of Influenza A Viruses

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Neumann, Gabriele; Kawaoka, Yoshihiro

2015-01-01

Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to ‘novel’ viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

Casein Kinase 1α Mediates the Degradation of Receptors for Type I and Type II Interferons Caused by Hemagglutinin of Influenza A Virus.

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Xia, Chuan; Wolf, Jennifer J; Vijayan, Madhuvanthi; Studstill, Caleb J; Ma, Wenjun; Hahm, Bumsuk

2018-04-01

Although influenza A virus (IAV) evades cellular defense systems to effectively propagate in the host, the viral immune-evasive mechanisms are incompletely understood. Our recent data showed that hemagglutinin (HA) of IAV induces degradation of type I IFN receptor 1 (IFNAR1). Here, we demonstrate that IAV HA induces degradation of type II IFN (IFN-γ) receptor 1 (IFNGR1), as well as IFNAR1, via casein kinase 1α (CK1α), resulting in the impairment of cellular responsiveness to both type I and II IFNs. IAV infection or transient HA expression induced degradation of both IFNGR1 and IFNAR1, whereas HA gene-deficient IAV failed to downregulate the receptors. IAV HA caused the phosphorylation and ubiquitination of IFNGR1, leading to the lysosome-dependent degradation of IFNGR1. Influenza viral HA strongly decreased cellular sensitivity to type II IFNs, as it suppressed the activation of STAT1 and the induction of IFN-γ-stimulated genes in response to exogenously supplied recombinant IFN-γ. Importantly, CK1α, but not p38 MAP kinase or protein kinase D2, was proven to be critical for HA-induced degradation of both IFNGR1 and IFNAR1. Pharmacologic inhibition of CK1α or small interfering RNA (siRNA)-based knockdown of CK1α repressed the degradation processes of both IFNGR1 and IFNAR1 triggered by IAV infection. Further, CK1α was shown to be pivotal for proficient replication of IAV. Collectively, the results suggest that IAV HA induces degradation of IFN receptors via CK1α, creating conditions favorable for viral propagation. Therefore, the study uncovers a new immune-evasive pathway of influenza virus. IMPORTANCE Influenza A virus (IAV) remains a grave threat to humans, causing seasonal and pandemic influenza. Upon infection, innate and adaptive immunity, such as the interferon (IFN) response, is induced to protect hosts against IAV infection. However, IAV seems to be equipped with tactics to evade the IFN-mediated antiviral responses, although the detailed

A spatial model of mosquito host-seeking behavior.

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Bree Cummins

Full Text Available Mosquito host-seeking behavior and heterogeneity in host distribution are important factors in predicting the transmission dynamics of mosquito-borne infections such as dengue fever, malaria, chikungunya, and West Nile virus. We develop and analyze a new mathematical model to describe the effect of spatial heterogeneity on the contact rate between mosquito vectors and hosts. The model includes odor plumes generated by spatially distributed hosts, wind velocity, and mosquito behavior based on both the prevailing wind and the odor plume. On a spatial scale of meters and a time scale of minutes, we compare the effectiveness of different plume-finding and plume-tracking strategies that mosquitoes could use to locate a host. The results show that two different models of chemotaxis are capable of producing comparable results given appropriate parameter choices and that host finding is optimized by a strategy of flying across the wind until the odor plume is intercepted. We also assess the impact of changing the level of host aggregation on mosquito host-finding success near the end of the host-seeking flight. When clusters of hosts are more tightly associated on smaller patches, the odor plume is narrower and the biting rate per host is decreased. For two host groups of unequal number but equal spatial density, the biting rate per host is lower in the group with more individuals, indicative of an attack abatement effect of host aggregation. We discuss how this approach could assist parameter choices in compartmental models that do not explicitly model the spatial arrangement of individuals and how the model could address larger spatial scales and other probability models for mosquito behavior, such as Lévy distributions.

Serpin functions in host-pathogen interactions

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Jialing Bao

2018-04-01

Full Text Available Serpins are a broadly distributed superfamily of protease inhibitors that are present in all kingdoms of life. The acronym, serpin, is derived from their function as potent serine proteases inhibitors. Early studies of serpins focused on their functions in haemostasis since modulating serine proteases activities are essential for coagulation. Additional research has revealed that serpins function in infection and inflammation, by modulating serine and cysteine proteases activities. The aim of this review is to summarize the accumulating findings and current understanding of the functions of serpins in host-pathogen interactions, serving as host defense proteins as well as pathogenic factors. We also discuss the potential crosstalk between host and pathogen serpins. We anticipate that future research will elucidate the therapeutic value of this novel target.

Transplantation of germ cells from glial cell line-derived neurotrophic factor-overexpressing mice to host testes depleted of endogenous spermatogenesis by fractionated irradiation

NARCIS (Netherlands)

Creemers, L. B.; Meng, X.; den Ouden, K.; van Pelt, A. M. M.; Izadyar, F.; Santoro, M.; Sariola, H.; de rooij, D. G.

2002-01-01

With a novel method of eliminating spermatogenesis in host animals, male germ cells isolated from mice with targeted overexpression of glial cell line-derived neurotrophic factor (GDNF) were transplanted to evaluate their ability to reproduce the phenotype previously found in the transgenic animals.

Variations on the larval incubation of Anodontites trapesialis (Unionoida, Mycetopodidae: Synergetic effect of the environmental factors and host availability

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CT. Callil

Full Text Available The unionid Anodontites trapesilais (Lamarck, 1819 like most freshwater mussels is a parasite of fish. So it is trivial to assume that the availability of hosts is an important factor for the maintenance of unionoid populations. What seems obvious is not always so easy to demonstrate. This study proposes to investigate the effects of abiotic and biotic variables related to the incubation of larvae in A. trapesialis. For this, we estimate different biological indexes and try to capture the dimensionality of the fish, along with the temporal variation of environmental variables. From the application of a CCA, it was demonstrated that there was a synchronicity among the factors and variables proposed here, and we infer that the flood pulse acts as a synergistic factor in this process.

Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

Energy Technology Data Exchange (ETDEWEB)

Strauch, Eva-Maria; Bernard, Steffen M.; La, David; Bohn, Alan J.; Lee, Peter S.; Anderson, Caitlin E.; Nieusma, Travis; Holstein, Carly A.; Garcia, Natalie K.; Hooper, Kathryn A.; Ravichandran, Rashmi; Nelson, Jorgen W.; Sheffler, William; Bloom, Jesse D.; Lee, Kelly K.; Ward, Andrew B.; Yager, Paul; Fuller, Deborah H.; Wilson, Ian A.; Baker , David (UWASH); (Scripps); (FHCRC)

2017-06-12

Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.

Occurrence of mannose resistant hemagglutinins in Escherichia coli strains isolated from porcine colibacillosis.

Science.gov (United States)

Truszczyński, M; Osek, J

1987-01-01

Three-hundred and fifty-eight E. coli strains isolated from piglets were tested for the presence of hemagglutinins by the use of the active hemagglutination test with or without mannose. Additionally 86 strains from the mentioned number of strains were investigated for the presence of common fimbriae using the same method but growing the strains in media especially suited for the development of this kind of fimbriae. These 358 strains and additionally 202 E. coli strains were tested using antisera for 987P and K88 antigens. It was found, using the active hemagglutination test, that 51.4% of the strains were hemagglutinating. The hemagglutinating strains carried the K88 antigen. All these strains were isolated from new-born and weaned piglets with enterotoxic form of colibacillosis, called also E. coli diarrhea. From cases of this form of colibacillosis originated also 26.7% of the strains in which common fimbriae (type 1) were detected. This result was obtained when the BHI medium was used for cultivation. In case of TSA medium only 2.3% of strains were positive. No specific or common fimbriae were found in strains recovered from septic form of colibacillosis and oedema disease (called also enterotoxaemic form of colibacillosis). No strain of 560 examined showed the presence of fimbrial 987P antigen.

Impact of Mutations in the Hemagglutinin of H10N7 Viruses Isolated from Seals on Virus Replication in Avian and Human Cells

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Anne Dittrich

2018-02-01

Full Text Available Wild birds are the reservoir for low-pathogenic avian influenza viruses, which are frequently transmitted to domestic birds and occasionally to mammals. In 2014, an H10N7 virus caused severe mortality in harbor seals in northeastern Europe. Although the hemagglutinin (HA of this virus was closely related to H10 of avian H10N4 virus, it possessed unique nonsynonymous mutations, particularly in the HA1 subunit in or adjacent to the receptor binding domain and proteolytic cleavage site. Here, the impact of these mutations on virus replication was studied in vitro. Using reverse genetics, an avian H10N4 virus was cloned, and nine recombinant viruses carrying one of eight unique mutations or the complete HA from the seal virus were rescued. Receptor binding affinity, replication in avian and mammalian cell cultures, cell-to-cell spread, and HA cleavability of these recombinant viruses were studied. Results show that wild-type recombinant H10N4 virus has high affinity to avian-type sialic acid receptors and no affinity to mammalian-type receptors. The H10N7 virus exhibits dual receptor binding affinity. Interestingly, Q220L (H10 numbering in the rim of the receptor binding pocket increased the affinity of the H10N4 virus to mammal-type receptors and completely abolished the affinity to avian-type receptors. No remarkable differences in cell-to-cell spread or HA cleavability were observed. All viruses, including the wild-type H10N7 virus, replicated at higher levels in chicken cells than in human cells. These results indicate that H10N7 acquired adaptive mutations (e.g., Q220L to enhance replication in mammals and retained replication efficiency in the original avian host.

Impact of Mutations in the Hemagglutinin of H10N7 Viruses Isolated from Seals on Virus Replication in Avian and Human Cells.

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Dittrich, Anne; Scheibner, David; Salaheldin, Ahmed H; Veits, Jutta; Gischke, Marcel; Mettenleiter, Thomas C; Abdelwhab, Elsayed M

2018-02-14

Wild birds are the reservoir for low-pathogenic avian influenza viruses, which are frequently transmitted to domestic birds and occasionally to mammals. In 2014, an H10N7 virus caused severe mortality in harbor seals in northeastern Europe. Although the hemagglutinin (HA) of this virus was closely related to H10 of avian H10N4 virus, it possessed unique nonsynonymous mutations, particularly in the HA1 subunit in or adjacent to the receptor binding domain and proteolytic cleavage site. Here, the impact of these mutations on virus replication was studied in vitro. Using reverse genetics, an avian H10N4 virus was cloned, and nine recombinant viruses carrying one of eight unique mutations or the complete HA from the seal virus were rescued. Receptor binding affinity, replication in avian and mammalian cell cultures, cell-to-cell spread, and HA cleavability of these recombinant viruses were studied. Results show that wild-type recombinant H10N4 virus has high affinity to avian-type sialic acid receptors and no affinity to mammalian-type receptors. The H10N7 virus exhibits dual receptor binding affinity. Interestingly, Q220L (H10 numbering) in the rim of the receptor binding pocket increased the affinity of the H10N4 virus to mammal-type receptors and completely abolished the affinity to avian-type receptors. No remarkable differences in cell-to-cell spread or HA cleavability were observed. All viruses, including the wild-type H10N7 virus, replicated at higher levels in chicken cells than in human cells. These results indicate that H10N7 acquired adaptive mutations (e.g., Q220L) to enhance replication in mammals and retained replication efficiency in the original avian host.

Dynamical System and Nonlinear Regression for Estimate Host-Parasitoid Relationship

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Ileana Miranda Cabrera

2010-01-01

Full Text Available The complex relationships of a crop with the pest, its natural enemies, and the climate factors exist in all the ecosystems, but the mathematic models has studied only some components to know the relation cause-effect. The most studied system has been concerned with the relationship pest-natural enemies such as prey-predator or host-parasitoid. The present paper shows a dynamical system for studying the relationship host-parasitoid (Diaphorina citri, Tamarixia radiata and shows that a nonlinear model permits the estimation of the parasite nymphs using nymphs healthy as the known variable. The model showed the functional answer of the parasitoid, in which a point arrives that its density is not augmented although the number host increases, and it becomes necessary to intervene in the ecosystem. A simple algorithm is used to estimate the parasitoids level using the priori relationship between the host and the climate factors and then the nonlinear model.

Coxsackievirus mutants that can bypass host factor PI4KIIIbeta and the need for high levels of PI4P lipids for replication

NARCIS (Netherlands)

van der Schaar, H.M.; van der Linden, L.; Lanke, K.H.W.; Strating, J.R.P.M.; Purstinger, G.; Vries, E. De; de Haan, C.A.; Neyts, J.; Kuppeveld, F.J.M. van

2012-01-01

RNA viruses can rapidly mutate and acquire resistance to drugs that directly target viral enzymes, which poses serious problems in a clinical context. Therefore, there is a growing interest in the development of antiviral drugs that target host factors critical for viral replication, since they are

Multiple factors and processes involved in host cell killing by bacteriophage Mu: characterization and mapping.

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Waggoner, B T; Marrs, C F; Howe, M M; Pato, M L

1984-07-15

The regions of bacteriophage Mu involved in host cell killing were determined by infection of a lambda-immune host with 12 lambda pMu-transducing phages carrying different amounts of Mu DNA beginning at the left end. Infecting lambda pMu phages containing 5.0 (+/- 0.2) kb or less of the left end of Mu DNA did not kill the lambda-immune host, whereas lambda pMu containing 5.1 kb did kill, thus locating the right end of the kil gene between approximately 5.0 and 5.1 kb. For the Kil+ phages the extent of killing increased as the multiplicity of infection (m.o.i.) increased. In addition, killing was also affected by the presence of at least two other regions of Mu DNA: one, located between 5.1 and 5.8 kb, decreased the extent of killing; the other, located between 6.3 and 7.9 kb, greatly increased host cell killing. Killing was also assayed after lambda pMu infection of a lambda-immune host carrying a mini-Mu deleted for most of the B gene and the middle region of Mu DNA. Complementation of mini-Mu replication by infecting B+ lambda pMu phages resulted in killing of the lambda-immune, mini-Mu-containing host, regardless of the presence or absence of the Mu kil gene. The extent of host cell killing increased as the m.o.i. of the infecting lambda pMu increased, and was further enhanced by both the presence of the kil gene and the region located between 6.3 and 7.9 kb. These distinct processes of kil-mediated killing in the absence of replication and non-kil-mediated killing in the presence of replication were also observed after induction of replication-deficient and kil mutant prophages, respectively.

Host Specificity of Salmonella typhimurium Deoxyribonucleic Acid Restriction and Modification

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Slocum, Harvey; Boyer, Herbert W.

1973-01-01

The restriction and modification genes of Salmonella typhimurium which lie near the thr locus were transferred to a restrictionless mutant of Escherichia coli. These genes were found to be allelic to the E. coli K, B, and A restriction and modification genes. E. coli recombinants with the restriction and modification host specificity of S. typhimurium restricted phage λ that had been modified by each of the seven known host specificities of E. coli at efficiency of plating levels of about 10−2. Phage λ modified with the S. typhimurium host specificity was restricted by six of the seven E. coli host specificities but not by the RII (fi− R-factor controlled) host specificity. It is proposed that the restriction and modification enzymes of this S. typhimurium host specificity have two substrates, one of which is a substrate for the RII host specificity enzymes. PMID:4570605

Ontology-based representation and analysis of host-Brucella interactions.

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Lin, Yu; Xiang, Zuoshuang; He, Yongqun

2015-01-01

Biomedical ontologies are representations of classes of entities in the biomedical domain and how these classes are related in computer- and human-interpretable formats. Ontologies support data standardization and exchange and provide a basis for computer-assisted automated reasoning. IDOBRU is an ontology in the domain of Brucella and brucellosis. Brucella is a Gram-negative intracellular bacterium that causes brucellosis, the most common zoonotic disease in the world. In this study, IDOBRU is used as a platform to model and analyze how the hosts, especially host macrophages, interact with virulent Brucella strains or live attenuated Brucella vaccine strains. Such a study allows us to better integrate and understand intricate Brucella pathogenesis and host immunity mechanisms. Different levels of host-Brucella interactions based on different host cell types and Brucella strains were first defined ontologically. Three important processes of virulent Brucella interacting with host macrophages were represented: Brucella entry into macrophage, intracellular trafficking, and intracellular replication. Two Brucella pathogenesis mechanisms were ontologically represented: Brucella Type IV secretion system that supports intracellular trafficking and replication, and Brucella erythritol metabolism that participates in Brucella intracellular survival and pathogenesis. The host cell death pathway is critical to the outcome of host-Brucella interactions. For better survival and replication, virulent Brucella prevents macrophage cell death. However, live attenuated B. abortus vaccine strain RB51 induces caspase-2-mediated proinflammatory cell death. Brucella-associated cell death processes are represented in IDOBRU. The gene and protein information of 432 manually annotated Brucella virulence factors were represented using the Ontology of Genes and Genomes (OGG) and Protein Ontology (PRO), respectively. Seven inference rules were defined to capture the knowledge of host

Population structure of Spodoptera frugiperda maize and rice host forms in South America: are they host strains?

NARCIS (Netherlands)

Juárez, M.L.; Schöfl, G.; Vera, M.T.; Vilardi, J.C.; Murúa, M.G.; Willink, E.; Hänniger, S.; Heckel, D.G.; Groot, A.T.

2014-01-01

Determining which factors contribute to the formation and maintenance of genetic divergence to evaluate their relative importance as a cause of biological differentiation is among the major challenges in evolutionary biology. In Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae) two host strains

Host nutrition alters the variance in parasite transmission potential.

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Vale, Pedro F; Choisy, Marc; Little, Tom J

2013-04-23

The environmental conditions experienced by hosts are known to affect their mean parasite transmission potential. How different conditions may affect the variance of transmission potential has received less attention, but is an important question for disease management, especially if specific ecological contexts are more likely to foster a few extremely infectious hosts. Using the obligate-killing bacterium Pasteuria ramosa and its crustacean host Daphnia magna, we analysed how host nutrition affected the variance of individual parasite loads, and, therefore, transmission potential. Under low food, individual parasite loads showed similar mean and variance, following a Poisson distribution. By contrast, among well-nourished hosts, parasite loads were right-skewed and overdispersed, following a negative binomial distribution. Abundant food may, therefore, yield individuals causing potentially more transmission than the population average. Measuring both the mean and variance of individual parasite loads in controlled experimental infections may offer a useful way of revealing risk factors for potential highly infectious hosts.

Hemagglutinin-specific neutralization of subacute sclerosing panencephalitis viruses.

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Miguel Ángel Muñoz-Alía

Full Text Available Subacute sclerosing panencephalitis (SSPE is a progressive, lethal complication of measles caused by particular mutants of measles virus (MeV that persist in the brain despite high levels of neutralizing antibodies. We addressed the hypothesis that antigenic drift is involved in the pathogenetic mechanism of SSPE by analyzing antigenic alterations in the MeV envelope hemagglutinin protein (MeV-H found in patients with SSPE in relation to major circulating MeV genotypes. To this aim, we obtained cDNA for the MeV-H gene from tissue taken at brain autopsy from 3 deceased persons with SSPE who had short (3-4 months, SMa79, average (3.5 years, SMa84, and long (18 years, SMa94 disease courses. Recombinant MeVs with a substituted MeV-H gene were generated by a reverse genetic system. Virus neutralization assays with a panel of anti-MeV-H murine monoclonal antibodies (mAbs or vaccine-immunized mouse anti-MeV-H polyclonal sera were performed to determine the antigenic relatedness. Functional and receptor-binding analysis of the SSPE MeV-H showed activity in a SLAM/nectin-4-dependent manner. Similar to our panel of wild-type viruses, our SSPE viruses showed an altered antigenic profile. Genotypes A, G3, and F (SSPE case SMa79 were the exception, with an intact antigenic structure. Genotypes D7 and F (SSPE SMa79 showed enhanced neutralization by mAbs targeting antigenic site IIa. Genotypes H1 and the recently reported D4.2 were the most antigenically altered genotypes. Epitope mapping of neutralizing mAbs BH015 and BH130 reveal a new antigenic site on MeV-H, which we designated Φ for its intermediate position between previously defined antigenic sites Ia and Ib. We conclude that SSPE-causing viruses show similar antigenic properties to currently circulating MeV genotypes. The absence of a direct correlation between antigenic changes and predisposition of a certain genotype to cause SSPE does not lend support to the proposed antigenic drift as a

Uncovering the drivers of host-associated microbiota with joint species distribution modelling.

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Björk, Johannes R; Hui, Francis K C; O'Hara, Robert B; Montoya, Jose M

2018-06-01

In addition to the processes structuring free-living communities, host-associated microbiota are directly or indirectly shaped by the host. Therefore, microbiota data have a hierarchical structure where samples are nested under one or several variables representing host-specific factors, often spanning multiple levels of biological organization. Current statistical methods do not accommodate this hierarchical data structure and therefore cannot explicitly account for the effect of the host in structuring the microbiota. We introduce a novel extension of joint species distribution models (JSDMs) which can straightforwardly accommodate and discern between effects such as host phylogeny and traits, recorded covariates such as diet and collection site, among other ecological processes. Our proposed methodology includes powerful yet familiar outputs seen in community ecology overall, including (a) model-based ordination to visualize and quantify the main patterns in the data; (b) variance partitioning to assess how influential the included host-specific factors are in structuring the microbiota; and (c) co-occurrence networks to visualize microbe-to-microbe associations. © 2018 John Wiley & Sons Ltd.

Pathogenic adaptations to host-derived antibacterial copper

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Chaturvedi, Kaveri S.; Henderson, Jeffrey P.

2014-01-01

Recent findings suggest that both host and pathogen manipulate copper content in infected host niches during infections. In this review, we summarize recent developments that implicate copper resistance as an important determinant of bacterial fitness at the host-pathogen interface. An essential mammalian nutrient, copper cycles between copper (I) (Cu+) in its reduced form and copper (II) (Cu2+) in its oxidized form under physiologic conditions. Cu+ is significantly more bactericidal than Cu2+ due to its ability to freely penetrate bacterial membranes and inactivate intracellular iron-sulfur clusters. Copper ions can also catalyze reactive oxygen species (ROS) generation, which may further contribute to their toxicity. Transporters, chaperones, redox proteins, receptors and transcription factors and even siderophores affect copper accumulation and distribution in both pathogenic microbes and their human hosts. This review will briefly cover evidence for copper as a mammalian antibacterial effector, the possible reasons for this toxicity, and pathogenic resistance mechanisms directed against it. PMID:24551598

Associate host in single-layer co-host polymer electrophosphorescent devices

International Nuclear Information System (INIS)

Wang Yuanmin; Teng Feng; Feng Bin; Wang Yongsheng; Xu Xurong

2006-01-01

The definition and role of 'host' in polymer LED materials are studied in the present work. 'Primary host' and 'associate host' have been proposed and the rules of how to select an associate host are reported. Based on our experiments and the analysis of the energy scheme of the devices, we suggest that the values of the lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) are critical determinant in selecting a suitable associate host. On one hand, the associate host should be a hole-blocking material. This can confine the excitons in the active layer. On the other hand, the associate host should have a suitable LUMO that is convenient for electrons to transport

Host cell proteins in biotechnology-derived products: A risk assessment framework.

Science.gov (United States)

de Zafra, Christina L Zuch; Quarmby, Valerie; Francissen, Kathleen; Vanderlaan, Martin; Zhu-Shimoni, Judith

2015-11-01

To manufacture biotechnology products, mammalian or bacterial cells are engineered for the production of recombinant therapeutic human proteins including monoclonal antibodies. Host cells synthesize an entire repertoire of proteins which are essential for their own function and survival. Biotechnology manufacturing processes are designed to produce recombinant therapeutics with a very high degree of purity. While there is typically a low residual level of host cell protein in the final drug product, under some circumstances a host cell protein(s) may copurify with the therapeutic protein and, if it is not detected and removed, it may become an unintended component of the final product. The purpose of this article is to enumerate and discuss factors to be considered in an assessment of risk of residual host cell protein(s) detected and identified in the drug product. The consideration of these factors and their relative ranking will lead to an overall risk assessment that informs decision-making around how to control the levels of host cell proteins. © 2015 Wiley Periodicals, Inc.

A human-infecting H10N8 influenza virus retains a strong preference for avian-type receptors

NARCIS (Netherlands)

Zhang, Heng; de Vries, Robert P; Tzarum, Netanel; Zhu, Xueyong; Yu, Wenli; McBride, Ryan; Paulson, James C; Wilson, Ian A

2015-01-01

Recent avian-origin H10N8 influenza A viruses that have infected humans pose a potential pandemic threat. Alterations in the viral surface glycoprotein, hemagglutinin (HA), typically are required for influenza A viruses to cross the species barrier for adaptation to a new host, but whether H10N8

The public health impact of avian influenza viruses.

Science.gov (United States)

Katz, J M; Veguilla, V; Belser, J A; Maines, T R; Van Hoeven, N; Pappas, C; Hancock, K; Tumpey, T M

2009-04-01

Influenza viruses with novel hemagglutinin and 1 or more accompanying genes derived from avian influenza viruses sporadically emerge in humans and have the potential to result in a pandemic if the virus causes disease and spreads efficiently in a population that lacks immunity to the novel hemagglutinin. Since 1997, multiple avian influenza virus subtypes have been transmitted directly from domestic poultry to humans and have caused a spectrum of human disease, from asymptomatic to severe and fatal. To assess the pandemic risk that avian influenza viruses pose, we have used multiple strategies to better understand the capacity of avian viruses to infect, cause disease, and transmit among mammals, including humans. Seroepidemiologic studies that evaluate the frequency and risk of human infection with avian influenza viruses in populations with exposure to domestic or wild birds can provide a better understanding of the pandemic potential of avian influenza subtypes. Investigations conducted in Hong Kong following the first H5N1 outbreak in humans in 1997 determined that exposure to poultry in live bird markets was a key risk factor for human disease. Among poultry workers, butchering and exposure to sick poultry were risk factors for antibody to H5 virus, which provided evidence for infection. A second risk assessment tool, the ferret, can be used to evaluate the level of virulence and potential for host-to-host transmission of avian influenza viruses in this naturally susceptible host. Avian viruses isolated from humans exhibit a level of virulence and transmissibility in ferrets that generally reflects that seen in humans. The ferret model thus provides a means to monitor emerging avian influenza viruses for pandemic risk, as well as to evaluate laboratory-generated reassortants and mutants to better understand the molecular basis of influenza virus transmissibility. Taken together, such studies provide valuable information with which we can assess the public

Purification, crystallization and preliminary X-ray analysis of SGR6054, a Streptomyces homologue of the mycobacterial integration host factor mIHF

International Nuclear Information System (INIS)

Nomoto, Ryohei; Tezuka, Takeaki; Miyazono, Ken-ichi; Tanokura, Masaru; Horinouchi, Sueharu; Ohnishi, Yasuo

2012-01-01

A Streptomyces homologue of the mycobacterial integration host factor mIHF was heterologously produced, purified and crystallized in the presence of a 16-mer duplex DNA by the sitting-drop vapour-diffusion method. The best crystal diffracted X-rays to 2.22 Å resolution and belonged to space group C2. The mycobacterial integration host factor (mIHF) is a small nonspecific DNA-binding protein that is essential for the growth of Mycobacterium smegmatis. mIHF homologues are widely distributed among Actinobacteria, and a Streptomyces homologue of mIHF is involved in control of sporulation and antibiotic production in S. coelicolor A3(2). Despite their important biological functions, a structure of mIHF or its homologues has not been elucidated to date. Here, the S. griseus mIHF homologue (SGR6054) was expressed and purified from Escherichia coli and crystallized in the presence of a 16-mer duplex DNA by the sitting-drop vapour-diffusion method. The plate-shaped crystal belonged to space group C2, with unit-cell parameters a = 88.53, b = 69.35, c = 77.71 Å, β = 96.63°, and diffracted X-rays to 2.22 Å resolution

Purification, crystallization and preliminary X-ray analysis of SGR6054, a Streptomyces homologue of the mycobacterial integration host factor mIHF

Energy Technology Data Exchange (ETDEWEB)

Nomoto, Ryohei; Tezuka, Takeaki; Miyazono, Ken-ichi; Tanokura, Masaru; Horinouchi, Sueharu; Ohnishi, Yasuo [Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan)

2012-08-31

A Streptomyces homologue of the mycobacterial integration host factor mIHF was heterologously produced, purified and crystallized in the presence of a 16-mer duplex DNA by the sitting-drop vapour-diffusion method. The best crystal diffracted X-rays to 2.22 Å resolution and belonged to space group C2. The mycobacterial integration host factor (mIHF) is a small nonspecific DNA-binding protein that is essential for the growth of Mycobacterium smegmatis. mIHF homologues are widely distributed among Actinobacteria, and a Streptomyces homologue of mIHF is involved in control of sporulation and antibiotic production in S. coelicolor A3(2). Despite their important biological functions, a structure of mIHF or its homologues has not been elucidated to date. Here, the S. griseus mIHF homologue (SGR6054) was expressed and purified from Escherichia coli and crystallized in the presence of a 16-mer duplex DNA by the sitting-drop vapour-diffusion method. The plate-shaped crystal belonged to space group C2, with unit-cell parameters a = 88.53, b = 69.35, c = 77.71 Å, β = 96.63°, and diffracted X-rays to 2.22 Å resolution.

Analysis of the Pantoea ananatis pan-genome reveals factors underlying its ability to colonize and interact with plant, insect and vertebrate hosts.

Science.gov (United States)

De Maayer, Pieter; Chan, Wai Yin; Rubagotti, Enrico; Venter, Stephanus N; Toth, Ian K; Birch, Paul R J; Coutinho, Teresa A

2014-05-27

Pantoea ananatis is found in a wide range of natural environments, including water, soil, as part of the epi- and endophytic flora of various plant hosts, and in the insect gut. Some strains have proven effective as biological control agents and plant-growth promoters, while other strains have been implicated in diseases of a broad range of plant hosts and humans. By analysing the pan-genome of eight sequenced P. ananatis strains isolated from different sources we identified factors potentially underlying its ability to colonize and interact with hosts in both the plant and animal Kingdoms. The pan-genome of the eight compared P. ananatis strains consisted of a core genome comprised of 3,876 protein coding sequences (CDSs) and a sizeable accessory genome consisting of 1,690 CDSs. We estimate that ~106 unique CDSs would be added to the pan-genome with each additional P. ananatis genome sequenced in the future. The accessory fraction is derived mainly from integrated prophages and codes mostly for proteins of unknown function. Comparison of the translated CDSs on the P. ananatis pan-genome with the proteins encoded on all sequenced bacterial genomes currently available revealed that P. ananatis carries a number of CDSs with orthologs restricted to bacteria associated with distinct hosts, namely plant-, animal- and insect-associated bacteria. These CDSs encode proteins with putative roles in transport and metabolism of carbohydrate and amino acid substrates, adherence to host tissues, protection against plant and animal defense mechanisms and the biosynthesis of potential pathogenicity determinants including insecticidal peptides, phytotoxins and type VI secretion system effectors. P. ananatis has an 'open' pan-genome typical of bacterial species that colonize several different environments. The pan-genome incorporates a large number of genes encoding proteins that may enable P. ananatis to colonize, persist in and potentially cause disease symptoms in a wide range of

The host immune response to Clostridium difficile infection

Science.gov (United States)

2013-01-01

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

Antibiotics and Host Responses in the Pathogenesis of Staphylococcus Aureus Infection

NARCIS (Netherlands)

J.W. Swierstra (Jasper)

2017-01-01

textabstractThe primary aim of the research described in this thesis was to gain more insight into host pathogen interaction between Staphylococcus aureus and the human host by specifically studying the IgG (subclass specific) humoral response against staphylococcal virulence factors in humans

Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells*

Science.gov (United States)

Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

2014-01-01

Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis. PMID:24398686

Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells.

Science.gov (United States)

Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

2014-02-28

Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis.

Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

Energy Technology Data Exchange (ETDEWEB)

Lammerts van Bueren,A.; Higgins, M.; Wang, D.; Burke, R.; Boraston, A.

2007-01-01

The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.

Orchestrating the Selection and Packaging of Genomic RNA by Retroviruses: An Ensemble of Viral and Host Factors

Science.gov (United States)

Kaddis Maldonado, Rebecca J.; Parent, Leslie J.

2016-01-01

Infectious retrovirus particles contain two copies of unspliced viral RNA that serve as the viral genome. Unspliced retroviral RNA is transcribed in the nucleus by the host RNA polymerase II and has three potential fates: (1) it can be spliced into subgenomic messenger RNAs (mRNAs) for the translation of viral proteins; or it can remain unspliced to serve as either (2) the mRNA for the translation of Gag and Gag–Pol; or (3) the genomic RNA (gRNA) that is packaged into virions. The Gag structural protein recognizes and binds the unspliced viral RNA to select it as a genome, which is selected in preference to spliced viral RNAs and cellular RNAs. In this review, we summarize the current state of understanding about how retroviral packaging is orchestrated within the cell and explore potential new mechanisms based on recent discoveries in the field. We discuss the cis-acting elements in the unspliced viral RNA and the properties of the Gag protein that are required for their interaction. In addition, we discuss the role of host factors in influencing the fate of the newly transcribed viral RNA, current models for how retroviruses distinguish unspliced viral mRNA from viral genomic RNA, and the possible subcellular sites of genomic RNA dimerization and selection by Gag. Although this review centers primarily on the wealth of data available for the alpharetrovirus Rous sarcoma virus, in which a discrete RNA packaging sequence has been identified, we have also summarized the cis- and trans-acting factors as well as the mechanisms governing gRNA packaging of other retroviruses for comparison. PMID:27657110

Influence of the host contact sequence on the outcome of competition among aspergillus flavus isolates during host tissue invasion.

Science.gov (United States)

Mehl, H L; Cotty, P J

2011-03-01

Biological control of aflatoxin contamination by Aspergillus flavus is achieved through competitive exclusion of aflatoxin producers by atoxigenic strains. Factors dictating the extent to which competitive displacement occurs during host infection are unknown. The role of initial host contact in competition between pairs of A. flavus isolates coinfecting maize kernels was examined. Isolate success during tissue invasion and reproduction was assessed by quantification of isolate-specific single nucleotide polymorphisms using pyrosequencing. Isolates were inoculated either simultaneously or 1 h apart. Increased success during competition was conferred to the first isolate to contact the host independent of that isolate's innate competitive ability. The first-isolate advantage decreased with the conidial concentration, suggesting capture of limited resources on kernel surfaces contributes to competitive exclusion. Attempts to modify access to putative attachment sites by either coating kernels with dead conidia or washing kernels with solvents did not influence the success of the first isolate, suggesting competition for limited attachment sites on kernel surfaces does not mediate first-isolate advantage. The current study is the first to demonstrate an immediate competitive advantage conferred to A. flavus isolates upon host contact and prior to either germ tube emergence or host colonization. This suggests the timing of host contact is as important to competition during disease cycles as innate competitive ability. Early dispersal to susceptible crop components may allow maintenance within A. flavus populations of genetic types with low competitive ability during host tissue invasion.

The Evolution of Clutch Size in Hosts of Avian Brood Parasites.

Science.gov (United States)

Medina, Iliana; Langmore, Naomi E; Lanfear, Robert; Kokko, Hanna

2017-11-01

Coevolution with avian brood parasites shapes a range of traits in their hosts, including morphology, behavior, and breeding systems. Here we explore whether brood parasitism is also associated with the evolution of host clutch size. Several studies have proposed that hosts of highly virulent parasites could decrease the costs of parasitism by evolving a smaller clutch size, because hosts with smaller clutches will lose fewer progeny when their clutch is parasitized. We describe a model of the evolution of clutch size, which challenges this logic and shows instead that an increase in clutch size (or no change) should evolve in hosts. We test this prediction using a broad-scale comparative analysis to ask whether there are differences in clutch size within hosts and between hosts and nonhosts. Consistent with our model, this analysis revealed that host species do not have smaller clutches and that hosts that incur larger costs from raising a parasite lay larger clutches. We suggest that brood parasitism might be an influential factor in clutch-size evolution and could potentially select for the evolution of larger clutches in host species.

Proteinaceous molecules mediating Bifidobacterium-host interactions

Directory of Open Access Journals (Sweden)

Lorena Ruiz

2016-08-01

Full Text Available 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.

Superparasitism Drives Heritable Symbiont Epidemiology and Host Sex Ratio in a Wasp.

Directory of Open Access Journals (Sweden)

Steven R Parratt

2016-06-01

Full Text Available Heritable microbial symbionts have profound impacts upon the biology of their arthropod hosts. Whilst our current understanding of the dynamics of these symbionts is typically cast within a framework of vertical transmission only, horizontal transmission has been observed in a number of cases. For instance, several symbionts can transmit horizontally when their parasitoid hosts share oviposition patches with uninfected conspecifics, a phenomenon called superparasitism. Despite this, horizontal transmission, and the host contact structures that facilitates it, have not been considered in heritable symbiont epidemiology. Here, we tested for the importance of host contact, and resulting horizontal transmission, for the epidemiology of a male-killing heritable symbiont (Arsenophonus nasoniae in parasitoid wasp hosts. We observed that host contact through superparasitism is necessary for this symbiont's spread in populations of its primary host Nasonia vitripennis, such that when superparasitism rates are high, A. nasoniae almost reaches fixation, causes highly female biased population sex ratios and consequently causes local host extinction. We further tested if natural interspecific variation in superparasitism behaviours predicted symbiont dynamics among parasitoid species. We found that A. nasoniae was maintained in laboratory populations of a closely related set of Nasonia species, but declined in other, more distantly related pteromalid hosts. The natural proclivity of a species to superparasitise was the primary factor determining symbiont persistence. Our results thus indicate that host contact behaviour is a key factor for heritable microbe dynamics when horizontal transmission is possible, and that 'reproductive parasite' phenotypes, such as male-killing, may be of secondary importance in the dynamics of such symbiont infections.

Host and Non-Host roots in rice: cellular and molecular approaches reveal differential responses to arbuscular mycorrhizal fungi.

Directory of Open Access Journals (Sweden)

Valentina eFiorilli

2015-08-01

Full Text Available Oryza sativa, a model plant for Arbuscular Mycorrhizal (AM symbiosis, has both host and non-host roots. Large lateral (LLR and fine lateral (FLR roots display opposite responses: LLR support AM colonization, but FLR do not. Our research aimed to study the molecular, morphological and physiological aspects related to the non-host behavior of FLR. RNA-seq analysis revealed that LLR and FLR displayed divergent expression profiles, including changes in many metabolic pathways. Compared with LLR, FLR showed down-regulation of genes instrumental for AM establishment and gibberellin signaling, and a higher expression of nutrient transporters. Consistent with the transcriptomic data, FLR had higher phosphorus content. Light and electron microscopy demonstrated that, surprisingly, in the Selenio cultivar, FLR have a two-layered cortex, which is theoretically compatible with AM colonization. According to RNA-seq, a gibberellin inhibitor treatment increased anticlinal divisions leading to a higher number of cortex cells in FLR.We propose that some of the differentially regulated genes that lead to the anatomical and physiological properties of the two root types also function as genetic factors regulating fungal colonization. The rice root apparatus offers a unique tool to study AM symbiosis, allowing direct comparisons of host and non-host roots in the same individual plant.

Truncation of a P1 leader proteinase facilitates potyvirus replication in a non-permissive host.

Science.gov (United States)

Shan, Hongying; Pasin, Fabio; Tzanetakis, Ioannis E; Simón-Mateo, Carmen; García, Juan Antonio; Rodamilans, Bernardo

2017-11-08

The Potyviridae family is a major group of plant viruses that includes c. 200 species, most of which have narrow host ranges. The potyvirid P1 leader proteinase self-cleaves from the remainder of the viral polyprotein and shows large sequence variability linked to host adaptation. P1 proteins can be classified as Type A or Type B on the basis, amongst other things, of their dependence or not on a host factor to develop their protease activity. In this work, we studied Type A proteases from the Potyviridae family, characterizing their host factor requirements. Our in vitro cleavage analyses of potyvirid P1 proteases showed that the N-terminal domain is relevant for host factor interaction and suggested that the C-terminal domain is also involved. In the absence of plant factors, the N-terminal end of Plum pox virus P1 antagonizes protease self-processing. We performed extended deletion mutagenesis analysis to define the N-terminal antagonistic domain of P1. In viral infections, removal of the P1 protease antagonistic domain led to a gain-of-function phenotype, strongly increasing local infection in a non-permissive host. Altogether, our results shed new insights into the adaptation and evolution of potyvirids. © 2017 BSPP AND JOHN WILEY & SONS LTD.

A mathematical modelling framework for linked within-host and between-host dynamics for infections with free-living pathogens in the environment.

Science.gov (United States)

Garira, Winston; Mathebula, Dephney; Netshikweta, Rendani

2014-10-01

In this study we develop a mathematical modelling framework for linking the within-host and between-host dynamics of infections with free-living pathogens in the environment. The resulting linked models are sometimes called immuno-epidemiological models. However, there is still no generalised framework for linking the within-host and between-host dynamics of infectious diseases. Furthermore, for infections with free-living pathogens in the environment, there is an additional stumbling block in that there is a gap in knowledge on how environmental factors (through water, air, soil, food, fomites, etc.) alter many aspects of such infections including susceptibility to infective dose, persistence of infection, pathogen shedding and severity of the disease. In this work, we link the two subsystems (within-host and between-host models) by identifying the within-host and between-host variables and parameters associated with the environmental dynamics of the pathogen and then design a feedback of the variables and parameters across the within-host and between-host models using human schistosomiasis as a case study. We study the mathematical properties of the linked model and show that the model is epidemiologically well-posed. Using results from the analysis of the endemic equilibrium expression, the disease reproductive number R0, and numerical simulations of the full model, we adequately account for the reciprocal influence of the linked within-host and between-host models. In particular, we illustrate that for human schistosomiasis, the outcome of infection at the individual level determines if, when and how much the individual host will further transmit the infectious agent into the environment, eventually affecting the spread of the infection in the host population. We expect the conceptual modelling framework developed here to be applicable to many infectious disease with free-living pathogens in the environment beyond the specific disease system of human

Host partitioning by parasites in an intertidal crustacean community.

Science.gov (United States)

Koehler, Anson V; Poulin, Robert

2010-10-01

Patterns of host use by parasites throughout a guild community of intermediate hosts can depend on several biological and ecological factors, including physiology, morphology, immunology, and behavior. We looked at parasite transmission in the intertidal crustacean community of Lower Portobello Bay, Dunedin, New Zealand, with the intent of: (1) mapping the flow of parasites throughout the major crustacean species, (2) identifying hosts that play the most important transmission role for each parasite, and (3) assessing the impact of parasitism on host populations. The most prevalent parasites found in 14 species of crustaceans (635 specimens) examined were the trematodes Maritrema novaezealandensis and Microphallus sp., the acanthocephalans Profilicollis spp., the nematode Ascarophis sp., and an acuariid nematode. Decapods were compatible hosts for M. novaezealandensis, while other crustaceans demonstrated lower host suitability as shown by high levels of melanized and immature parasite stages. Carapace thickness, gill morphology, and breathing style may contribute to the differential infection success of M. novaezealandensis and Microphallus sp. in the decapod species. Parasite-induced host mortality appears likely with M. novaezealandensis in the crabs Austrohelice crassa, Halicarcinus varius, Hemigrapsus sexdentatus, and Macrophthalmus hirtipes, and also with Microphallus sp. in A. crassa. Overall, the different parasite species make different use of available crustacean intermediate hosts and possibly contribute to intertidal community structure.

Host Diet Affects the Morphology of Monarch Butterfly Parasites.

Science.gov (United States)

Hoang, Kevin; Tao, Leiling; Hunter, Mark D; de Roode, Jacobus C

2017-06-01

Understanding host-parasite interactions is essential for ecological research, wildlife conservation, and health management. While most studies focus on numerical traits of parasite groups, such as changes in parasite load, less focus is placed on the traits of individual parasites such as parasite size and shape (parasite morphology). Parasite morphology has significant effects on parasite fitness such as initial colonization of hosts, avoidance of host immune defenses, and the availability of resources for parasite replication. As such, understanding factors that affect parasite morphology is important in predicting the consequences of host-parasite interactions. Here, we studied how host diet affected the spore morphology of a protozoan parasite ( Ophryocystis elektroscirrha ), a specialist parasite of the monarch butterfly ( Danaus plexippus ). We found that different host plant species (milkweeds; Asclepias spp.) significantly affected parasite spore size. Previous studies have found that cardenolides, secondary chemicals in host plants of monarchs, can reduce parasite loads and increase the lifespan of infected butterflies. Adding to this benefit of high cardenolide milkweeds, we found that infected monarchs reared on milkweeds of higher cardenolide concentrations yielded smaller parasites, a potentially hidden characteristic of cardenolides that may have important implications for monarch-parasite interactions.

Host-pathogen interplay of Haemophilus ducreyi.

Science.gov (United States)

Janowicz, Diane M; Li, Wei; Bauer, Margaret E

2010-02-01

Haemophilus ducreyi, the causative agent of the sexually transmitted infection chancroid, is primarily a pathogen of human skin. During infection, H. ducreyi thrives extracellularly in a milieu of professional phagocytes and other antibacterial components of the innate and adaptive immune responses. This review summarizes our understanding of the interplay between this pathogen and its host that leads to development and persistence of disease. H. ducreyi expresses key virulence mechanisms to resist host defenses. The secreted LspA proteins are tyrosine-phosphorylated by host kinases, which may contribute to their antiphagocytic effector function. The serum resistance and adherence functions of DsrA map to separate domains of this multifunctional virulence factor. An influx transporter protects H. ducreyi from killing by the antimicrobial peptide LL37. Regulatory genes have been identified that may coordinate virulence factor expression during disease. Dendritic cells and natural killer cells respond to H. ducreyi and may be involved in determining the differential outcomes of infection observed in humans. A human model of H. ducreyi infection has provided insights into virulence mechanisms that allow this human-specific pathogen to survive immune pressures. Components of the human innate immune system may also determine the ultimate fate of H. ducreyi infection by driving either clearance of the organism or an ineffective response that allows disease progression.

New host, geographical records, and factors affecting the prevalence of helminths infection from synanthropic rodents in Yucatán, Mexico

OpenAIRE

Panti-May J. A.; Palomo-Arjona E.; Gurubel-González Y.; Torres-Castro M. A.; Vidal-Martínez V. M.; Machain-Williams C.; Hernández-Betancourt S. F.; Del Rosario Robles M.

2017-01-01

The aim of this paper was to study the occurrence of helminths in Mus musculus and Rattus rattus from urban, suburban and rural settlements in Yucatán, Mexico; and to analyse the host factors (e.g. sex) related to helminths’ distribution. Helminths in a total of 279 rodents were surveyed by visual examination of the liver for metacestodes and faecal examination for helminth eggs using the formalin-ethyl acetate sedimentation technique. The cestodes Hydatigera taeniaeformis (metacestodes detec...

Distribution of intermediate host snails of schistosomiasis and fascioliasis in relation to environmental factors during the dry season in the Tchologo region, Côte d'Ivoire

Science.gov (United States)

Krauth, Stefanie J.; Wandel, Nathalie; Traoré, Seïdinan I.; Vounatsou, Penelope; Hattendorf, Jan; Achi, Louise Y.; McNeill, Kristopher; N'Goran, Eliézer K.; Utzinger, Jürg

2017-10-01

Snail-borne trematodiases, such as fascioliasis and schistosomiasis, belong to the neglected tropical diseases; yet, millions of people and livestock are affected. The spatial and temporal distribution of intermediate host snails plays an important role in the epidemiology and control of trematodiases. Snail distribution is influenced by numerous environmental and anthropomorphic factors. The aim of this study was to assess the distribution and constitution of the snail fauna during the dry season in constructed and natural water bodies in the Tchologo region, northern Côte d'Ivoire, and to relate these findings to environmental factors and human infections. Snails were collected using standard procedures and environmental parameters were assessed from a total of 50 water bodies in and around 30 randomly selected villages. A canonical correspondence analysis was performed to establish the relationship between snail occurrence and environmental factors. Furthermore, a total of 743 people from the same 30 villages and nearby settlements were invited for stool and urine examination for the diagnosis of Fasciola spp., Schistosoma haematobium and Schistosoma mansoni. Snails of medical importance of the genera Biomphalaria, Bulinus, Lymnaea and Physa were found. Differences in snail occurrence from sites sampled in December 2014 and snails sampled in February 2015, as well as between the northern and southern part of the study area, were revealed. Various environmental factors, such as temperature and human activities, were related to the occurrence of intermediate host snail species in the region. Only 2.3% of human participants tested positive for schistosomiasis, while no Fasciola eggs were found in stool samples. We conclude that intermediate host snails of Fasciola and Schistosoma co-occur in water bodies in the Tchologo region and that the distribution of these snails correlates not only with environmental factors, but also with the presence of humans and animals

Resistance to Plum pox virus strain C in Arabidopsis thaliana and Chenopodium foetidum involves genome-linked viral protein and other viral determinants and might depend on compatibility with host translation initiation factors.

Science.gov (United States)

Calvo, María; Martínez-Turiño, Sandra; García, Juan Antonio

2014-11-01

Research performed on model herbaceous hosts has been useful to unravel the molecular mechanisms that control viral infections. The most common Plum pox virus (PPV) strains are able to infect Nicotiana species as well as Chenopodium and Arabidopsis species. However, isolates belonging to strain C (PPV-C) that have been adapted to Nicotiana spp. are not infectious either in Chenopodium foetidum or in Arabidopsis thaliana. In order to determine the mechanism underlying this interesting host-specific behavior, we have constructed chimerical clones derived from Nicotiana-adapted PPV isolates from the D and C strains, which differ in their capacity to infect A. thaliana and C. foetidum. With this approach, we have identified the nuclear inclusion a protein (VPg+Pro) as the major pathogenicity determinant that conditions resistance in the presence of additional secondary determinants, different for each host. Genome-linked viral protein (VPg) mutations similar to those involved in the breakdown of eIF4E-mediated resistance to other potyviruses allow some PPV chimeras to infect A. thaliana. These results point to defective interactions between a translation initiation factor and the viral VPg as the most probable cause of host-specific incompatibility, in which other viral factors also participate, and suggest that complex interactions between multiple viral proteins and translation initiation factors not only define resistance to potyviruses in particular varieties of susceptible hosts but also contribute to establish nonhost resistance.

The Use of Arabidopsis to Study Interactions between Parasitic Angiosperms and Their Plant Hosts

Science.gov (United States)

Goldwasser, Y.; Westwood, J. H.; Yoder, J. I.

2002-01-01

Parasitic plants invade host plants in order to rob them of water, minerals and nutrients. The consequences to the infected hosts can be debilitating and some of the world's most pernicious agricultural weeds are parasitic. Parasitic genera of the Scrophulariaceae and Orobanchaceae directly invade roots of neighboring plants via underground structures called haustoria. The mechanisms by which these parasites identify and associate with host plants present unsurpassed opportunities for studying chemical signaling in plant-plant interactions. Seeds of some parasites require specific host factors for efficient germination, thereby insuring the availability of an appropriate host root prior to germination. A second set of signal molecules is required to induce haustorium development and the beginning of heterotrophy. Later stages in parasitism also require the presence of host factors, although these have not yet been well characterized. Arabidopsis is being used as a model host plant to identify genetic loci associated with stimulating parasite germination, haustorium development, and parasite support. Arabidopsis is also being employed to explore how host plants respond to parasite attack. Current methodologies and recent findings in Arabidopsis – parasitic plant interactions will be discussed. PMID:22303205

Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut.

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Vincent Raquin

2017-12-01

Full Text Available Dengue virus (DENV causes more human infections than any other mosquito-borne virus. The current lack of antiviral strategies has prompted genome-wide screens for host genes that are required for DENV infectivity. Earlier transcriptomic studies that identified DENV host factors in the primary vector Aedes aegypti used inbred laboratory colonies and/or pools of mosquitoes that erase individual variation. Here, we performed transcriptome sequencing on individual midguts in a field-derived Ae. aegypti population to identify new candidate host factors modulating DENV replication. We analyzed the transcriptomic data using an approach that accounts for individual co-variation between viral RNA load and gene expression. This approach generates a prediction about the agonist or antagonist effect of candidate genes on DENV replication based on the sign of the correlation between gene expression and viral RNA load. Using this method, we identified 39 candidate genes that went undetected by conventional pairwise comparison of gene expression levels between DENV-infected midguts and uninfected controls. Only four candidate genes were detected by both methods, emphasizing their complementarity. We demonstrated the value of our approach by functional validation of a candidate agonist gene encoding a sterol regulatory element-binding protein (SREBP, which was identified by correlation analysis but not by pairwise comparison. We confirmed that SREBP promotes DENV infection in the midgut by RNAi-mediated gene knockdown in vivo. We suggest that our approach for transcriptomic analysis can empower genome-wide screens for potential agonist or antagonist factors by leveraging inter-individual variation in gene expression. More generally, this method is applicable to a wide range of phenotypic traits displaying inter-individual variation.

Optimal control issues in plant disease with host demographic factor and botanical fungicides

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Anggriani, N.; Mardiyah, M.; Istifadah, N.; Supriatna, A. K.

2018-03-01

In this paper, we discuss a mathematical model of plant disease with the effect of fungicide. We assume that the fungicide is given as a preventive treatment to infectious plants. The model is constructed based on the development of the disease in which the monomolecular is monocyclic. We show the value of the Basic Reproduction Number (BRN) ℛ0 of the plant disease transmission. The BRN is computed from the largest eigenvalue of the next generation matrix of the model. The result shows that in the region where ℛ0 greater than one there is a single stable endemic equilibrium. However, in the region where ℛ0 less than one this endemic equilibrium becomes unstable. The dynamics of the model is highly sensitive to changes in contact rate and infectious period. We also discuss the optimal control of the infected plant host by considering a preventive treatment aimed at reducing the infected host plant. The obtaining optimal control shows that it can reduce the number of infected hosts compared to that without control. Some numerical simulations are also given to illustrate our analytical results.

Initial Gut Microbial Composition as a Key Factor Driving Host Response to Antibiotic Treatment, as Exemplified by the Presence or Absence of Commensal Escherichia coli.

Science.gov (United States)

Ju, Tingting; Shoblak, Yasmeen; Gao, Yanhua; Yang, Kaiyuan; Fouhse, Janelle; Finlay, B Brett; So, Yee Wing; Stothard, Paul; Willing, Benjamin P

2017-09-01

Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3β (Reg3β) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3β and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies. IMPORTANCE This work provides an understanding of variability in studies where

Divergent genetic evolution of hemagglutinin in influenza A H1N1 and A H1N2 subtypes isolated in the south-France since the winter of 2001-2002.

Science.gov (United States)

Al Faress, Shaker; Cartet, Gaëlle; Ferraris, Olivier; Norder, Helene; Valette, Martine; Lina, Bruno

2005-07-01

Influenza A viruses are divided into subtypes based on their hemagglutinin (H1 to H15) and neuraminidase (N1 to N9) glycoproteins. Of these, three A subtypes H1N1, H3N2 and H1N2 circulate in the human population. Influenza A viruses display a high antigenic variability called "antigenic drift" which allows the virus to escape antibody neutralization. Evaluate the mutations apparition that might predict a divergent antigenic evolution of hemagglutinin in influenza A H1N1 and A H1N2 viruses. During the three winters of 2001-2002 to 2003-2004, 58 A H1N1 and 23 A H1N2 subtypes have been isolated from patients with influenza-like illness in the south of France. The HA1 region was analyzed by RT-PCR and subsequently sequenced to compare the HA1 genetic evolution of influenza A H1N1 and A H1N2 subtypes. Our results showed that 28 amino acid substitutions have accumulated in the HA1 region since the circulation of A/New Caledonia/20/99-like viruses in France. Of these, fifteen were located in four antigenic sites (B, C, D and E). Six of them were observed only in the A H1N2 isolates, six only in the A H1N1 isolates and three in both subtypes. Furthermore, nine of twenty two A H1N2 isolates from the winter of 2002-2003 shared a T90A amino acid change which has not been observed in any A H1N1 isolate; resulting in the introduction of a new glycosylation site close to the antigenic site E. This might mask some antigenic E determinants and therefore, modify the A H1N2 antigenicity. The divergent genetic evolution of hemagglutinin may ultimately lead to a significant different antigenicity between A H1N1 and A H1N2 subtypes that would require the introduction of a new subtype in the vaccine batches.

Female genital tract graft-versus-host disease: incidence, risk factors and recommendations for management.

Science.gov (United States)

Zantomio, D; Grigg, A P; MacGregor, L; Panek-Hudson, Y; Szer, J; Ayton, R

2006-10-01

Female genital tract graft-versus-host disease (GVHD) is an under-recognized complication of allogeneic stem cell transplantation impacting on quality of life. We describe a prospective surveillance programme for female genital GVHD to better characterize incidence, risk factors and clinical features and the impact of a structured intervention policy. A retrospective audit was conducted on the medical records of all female transplant recipients surviving at least 6 months at a single centre over a 5-year period. Patients commenced topical vaginal oestrogen early post transplant with hormone replacement as appropriate for age, prior menopausal status and co-morbidities. A genital tract management programme included regular gynaecological review and self-maintenance of vaginal capacity by dilator or intercourse. The incidence of genital GVHD was 35% (95% confidence interval (CI) (25, 50%)) at 1 year and 49% (95% CI (36, 63%)) at 2 years. Topical therapy was effective in most cases; no patient required surgical intervention to divide vaginal adhesions. The main risk factor was stem cell source with peripheral blood progenitor cells posing a higher risk than marrow (hazard ratio=3.07 (1.22, 7.73), P=0.017). Extensive GVHD in other organs was a common association. We conclude that female genital GVHD is common, and early detection and commencement of topical immunosuppression with dilator use appears to be highly effective at preventing progression.

Systemic and oral immunogenicity of hemagglutinin protein of rinderpest virus expressed by transgenic peanut plants in a mouse model

International Nuclear Information System (INIS)

Khandelwal, Abha; Renukaradhya, G.J.; Rajasekhar, M.; Sita, G. Lakshmi; Shaila, M.S.

2004-01-01

Rinderpest causes a devastating disease, often fatal, in wild and domestic ruminants. It has been eradicated successfully using a live, attenuated vaccine from most part of the world leaving a few foci of disease in parts of Africa, the Middle East, and South Asia. We have developed transgenic peanut (Arachis hypogaea L.) plants expressing hemagglutinin (H) protein of rinderpest virus (RPV), which is antigenically authentic. In this work, we have evaluated the immunogenicity of peanut-expressed H protein using mouse model, administered parenterally as well as orally. Intraperitoneal immunization of mice with the transgenic peanut extract elicited antibody response specific to H. These antibodies neutralized virus infectivity in vitro. Oral immunization of mice with transgenic peanut induced H-specific serum IgG and IgA antibodies. The systemic and oral immunogenicity of plant-derived H in absence of any adjuvant indicates the potential of edible vaccine for rinderpest

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

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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.

Host genotype is an important determinant of the cereal phyllosphere mycobiome

DEFF Research Database (Denmark)

Sapkota, Rumakanta; Knorr, Kamilla; Jørgensen, Lise Nistrup

2015-01-01

The phyllosphere mycobiome in cereals is an important determinant of crop health. However, an understanding of the factors shaping this community is lacking. Fungal diversity in leaves from a range of cultivars of winter wheat (Triticum aestivum), winter and spring barley (Hordeum vulgare...... and location have minor effects. We found many host-specific fungal pathogens, but also a large diversity of fungi that were relatively insensitive to host genetic background, indicating that host-specific pathogens live in a 'sea' of nonspecific fungi....

Stress responses in Streptococcus species and their effects on the host.

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Nguyen, Cuong Thach; Park, Sang-Sang; Rhee, Dong-Kwon

2015-11-01

Streptococci cause a variety of diseases, such as dental caries, pharyngitis, meningitis, pneumonia, bacteremia, endocarditis, erysipelas, and necrotizing fasciitis. The natural niche of this genus of bacteria ranges from the mouth and nasopharynx to the skin, indicating that the bacteria will inevitably be subjected to environmental changes during invasion into the host, where it is exposed to the host immune system. Thus, the Streptococcus-host interaction determines whether bacteria are cleared by the host's defenses or whether they survive after invasion to cause serious diseases. If this interaction was to be deciphered, it could aid in the development of novel preventive and therapeutic agents. Streptococcus species possess many virulent factors, such as peroxidases and heat-shock proteins (HSPs), which play key roles in protecting the bacteria from hostile host environments. This review will discuss insights into the mechanism(s) by which streptococci adapt to host environments. Additionally, we will address how streptococcal infections trigger host stress responses; however, the mechanism by which bacterial components modulate host stress responses remains largely unknown.

Differential Rickettsial Transcription in Bloodfeeding and Non-Bloodfeeding Arthropod Hosts.

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Victoria I Verhoeve

Full Text Available Crucial factors influencing the epidemiology of Rickettsia felis rickettsiosis include pathogenesis and transmission. Detection of R. felis DNA in a number of arthropod species has been reported, with characterized isolates, R. felis strain LSU and strain LSU-Lb, generated from the cat flea, Ctenocephalides felis, and the non-hematophagous booklouse, Liposcelis bostrychophila, respectively. While it is realized that strain influence on host biology varies, the rickettsial response to these distinct host environments remained undefined. To identify a panel of potential rickettsial transmission determinants in the cat flea, the transcriptional profile for these two strains of R. felis were compared in their arthropod hosts using RNAseq. Rickettsial genes with increased transcription in the flea as compared to the booklouse were identified. Genes previously associated with bacterial virulence including LPS biosynthesis, Type IV secretion system, ABC transporters, and a toxin-antitoxin system were selected for further study. Transcription of putative virulence-associated genes was determined in a flea infection bioassay for both strains of R. felis. A host-dependent transcriptional profile during bloodfeeding, specifically, an increased expression of selected transcripts in newly infected cat fleas and flea feces was detected when compared to arthropod cell culture and incubation in vertebrate blood. Together, these studies have identified novel, host-dependent rickettsial factors that likely contribute to successful horizontal transmission by bloodfeeding arthropods.

Histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and alters HagB-induced chemokine responses

Science.gov (United States)

Borgwardt, Derek S.; Martin, Aaron D.; van Hemert, Jonathan R.; Yang, Jianyi; Fischer, Carol L.; Recker, Erica N.; Nair, Prashant R.; Vidva, Robinson; Chandrashekaraiah, Shwetha; Progulske-Fox, Ann; Drake, David; Cavanaugh, Joseph E.; Vali, Shireen; Zhang, Yang; Brogden, Kim A.

2014-01-01

Histatins are human salivary gland peptides with anti-microbial and anti-inflammatory activities. In this study, we hypothesized that histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and attenuates HagB-induced chemokine responses in human myeloid dendritic cells. Histatin 5 bound to immobilized HagB in a surface plasmon resonance (SPR) spectroscopy-based biosensor system. SPR spectroscopy kinetic and equilibrium analyses, protein microarray studies, and I-TASSER structural modeling studies all demonstrated two histatin 5 binding sites on HagB. One site had a stronger affinity with a KD1 of 1.9 μM and one site had a weaker affinity with a KD2 of 60.0 μM. Binding has biological implications and predictive modeling studies and exposure of dendritic cells both demonstrated that 20.0 μM histatin 5 attenuated (p < 0.05) 0.02 μM HagB-induced CCL3/MIP-1α, CCL4/MIP-1β, and TNFα responses. Thus histatin 5 is capable of attenuating chemokine responses, which may help control oral inflammation.

Effects of shortened host life span on the evolution of parasite life history and virulence in a microbial host-parasite system

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Koella Jacob C

2009-03-01

Full Text Available Abstract Background Ecological factors play an important role in the evolution of parasite exploitation strategies. A common prediction is that, as shorter host life span reduces future opportunities of transmission, parasites compensate with an evolutionary shift towards earlier transmission. They may grow more rapidly within the host, have a shorter latency time and, consequently, be more virulent. Thus, increased extrinsic (i.e., not caused by the parasite host mortality leads to the evolution of more virulent parasites. To test these predictions, we performed a serial transfer experiment, using the protozoan Paramecium caudatum and its bacterial parasite Holospora undulata. We simulated variation in host life span by killing hosts after 11 (early killing or 14 (late killing days post inoculation; after killing, parasite transmission stages were collected and used for a new infection cycle. Results After 13 cycles (≈ 300 generations, parasites from the early-killing treatment were less infectious, but had shorter latency time and higher virulence than those from the late-killing treatment. Overall, shorter latency time was associated with higher parasite loads and thus presumably with more rapid within-host replication. Conclusion The analysis of the means of the two treatments is thus consistent with theory, and suggests that evolution is constrained by trade-offs between virulence, transmission and within-host growth. In contrast, we found little evidence for such trade-offs across parasite selection lines within treatments; thus, to some extent, these traits may evolve independently. This study illustrates how environmental variation (experienced by the host can lead to the evolution of distinct parasite strategies.

Host-selective toxins of Pyrenophora tritici-repentis induce common responses associated with host susceptibility.

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Iovanna Pandelova

Full Text Available Pyrenophora tritici-repentis (Ptr, a necrotrophic fungus and the causal agent of tan spot of wheat, produces one or a combination of host-selective toxins (HSTs necessary for disease development. The two most studied toxins produced by Ptr, Ptr ToxA (ToxA and Ptr ToxB (ToxB, are proteins that cause necrotic or chlorotic symptoms respectively. Investigation of host responses induced by HSTs provides better insight into the nature of the host susceptibility. Microarray analysis of ToxA has provided evidence that it can elicit responses similar to those associated with defense. In order to evaluate whether there are consistent host responses associated with susceptibility, a similar analysis of ToxB-induced changes in the same sensitive cultivar was conducted. Comparative analysis of ToxA- and ToxB-induced transcriptional changes showed that similar groups of genes encoding WRKY transcription factors, RLKs, PRs, components of the phenylpropanoid and jasmonic acid pathways are activated. ROS accumulation and photosystem dysfunction proved to be common mechanism-of-action for these toxins. Despite similarities in defense responses, transcriptional and biochemical responses as well as symptom development occur more rapidly for ToxA compared to ToxB, which could be explained by differences in perception as well as by differences in activation of a specific process, for example, ethylene biosynthesis in ToxA treatment. Results of this study suggest that perception of HSTs will result in activation of defense responses as part of a susceptible interaction and further supports the hypothesis that necrotrophic fungi exploit defense responses in order to induce cell death.

Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors.

Science.gov (United States)

Holtan, Shernan G; Khera, Nandita; Levine, John E; Chai, Xiaoyu; Storer, Barry; Liu, Hien D; Inamoto, Yoshihiro; Chen, George L; Mayer, Sebastian; Arora, Mukta; Palmer, Jeanne; Flowers, Mary E D; Cutler, Corey S; Lukez, Alexander; Arai, Sally; Lazaryan, Aleksandr; Newell, Laura F; Krupski, Christa; Jagasia, Madan H; Pusic, Iskra; Wood, William; Renteria, Anne S; Yanik, Gregory; Hogan, William J; Hexner, Elizabeth; Ayuk, Francis; Holler, Ernst; Watanaboonyongcharoen, Phandee; Efebera, Yvonne A; Ferrara, James L M; Panoskaltsis-Mortari, Angela; Weisdorf, Daniel; Lee, Stephanie J; Pidala, Joseph

2016-11-10

Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n = 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n = 55) and controls (n = 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic GVHD. © 2016 by The American Society of Hematology.

Factors affecting virus dynamics and microbial host-virus interactions in marine environments

NARCIS (Netherlands)

Mojica, K.D.A.; Brussaard, C.P.D.

2014-01-01

Marine microorganisms constitute the largest percentage of living biomass and serve as the major driving force behind nutrient and energy cycles. While viruses only comprise a small percentage of this biomass (i.e., 5%), they dominate in numerical abundance and genetic diversity. Through host

Trophic relationships between the parasitic plant species Phelipanche ramosa (L. and different hosts depending on host phenological stage and host growth rate

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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

Structural differences between the avian and human H7N9 hemagglutinin proteins are attributable to modifications in salt bridge formation: a computational study with implications in viral evolution.

Science.gov (United States)

Cueno, Marni E; Imai, Kenichi; Tamura, Muneaki; Ochiai, Kuniyasu

2013-01-01

Influenza A hemagglutinin (HA) is a homotrimeric glycoprotein composed of a fibrous globular stem supporting a globular head containing three sialic acid binding sites responsible for infection. The H7N9 strain has consistently infected an avian host, however, the novel 2013 strain is now capable of infecting a human host which would imply that the HA in both strains structurally differ. A better understanding of the structural differences between the avian and human H7N9 strains may shed light into viral evolution and transmissibility. In this study, we elucidated the structural differences between the avian and human H7N9 strains. Throughout the study, we generated HA homology models, verified the quality of each model, superimposed HA homology models to determine structural differences, and, likewise, elucidated the probable cause for these structural differences. We detected two different types of structural differences between the novel H7N9 human and representative avian strains, wherein, one type (Pattern-1) showed three non-overlapping regions while the other type (Pattern-2) showed only one non-overlapping region. In addition, we found that superimposed HA homology models exhibiting Pattern-1 contain three non-overlapping regions designated as: Region-1 (S1571-A1601); Region-3 (R2621-S2651); and Region-4 (S2701-D2811), whereas, superimposed HA homology models showing Pattern-2 only contain one non-overlapping region designated as Region-2 (S1371-S1451). We attributed the two patterns we observed to either the presence of salt bridges involving the E1141 residue or absence of the R1411:D771 salt bridge. Interestingly, comparison between the human H7N7 and H7N9 HA homology models showed high structural similarity. We propose that the putative absence of the R1411:D771 salt bridge coupled with the putative presence of the E1141:R2621 and E1141:K2641 salt bridges found in the 2013 H7N9 HA homology model is associated to human-type receptor binding. This

Structural differences between the avian and human H7N9 hemagglutinin proteins are attributable to modifications in salt bridge formation: a computational study with implications in viral evolution.

Directory of Open Access Journals (Sweden)

Marni E Cueno

Full Text Available Influenza A hemagglutinin (HA is a homotrimeric glycoprotein composed of a fibrous globular stem supporting a globular head containing three sialic acid binding sites responsible for infection. The H7N9 strain has consistently infected an avian host, however, the novel 2013 strain is now capable of infecting a human host which would imply that the HA in both strains structurally differ. A better understanding of the structural differences between the avian and human H7N9 strains may shed light into viral evolution and transmissibility. In this study, we elucidated the structural differences between the avian and human H7N9 strains. Throughout the study, we generated HA homology models, verified the quality of each model, superimposed HA homology models to determine structural differences, and, likewise, elucidated the probable cause for these structural differences. We detected two different types of structural differences between the novel H7N9 human and representative avian strains, wherein, one type (Pattern-1 showed three non-overlapping regions while the other type (Pattern-2 showed only one non-overlapping region. In addition, we found that superimposed HA homology models exhibiting Pattern-1 contain three non-overlapping regions designated as: Region-1 (S1571-A1601; Region-3 (R2621-S2651; and Region-4 (S2701-D2811, whereas, superimposed HA homology models showing Pattern-2 only contain one non-overlapping region designated as Region-2 (S1371-S1451. We attributed the two patterns we observed to either the presence of salt bridges involving the E1141 residue or absence of the R1411:D771 salt bridge. Interestingly, comparison between the human H7N7 and H7N9 HA homology models showed high structural similarity. We propose that the putative absence of the R1411:D771 salt bridge coupled with the putative presence of the E1141:R2621 and E1141:K2641 salt bridges found in the 2013 H7N9 HA homology model is associated to human-type receptor binding

Plasticity in host utilization by two host-associated populations of Aphis gossypii Glover.

Science.gov (United States)

Barman, A K; Gadhave, K R; Dutta, B; Srinivasan, R

2018-06-01

Biological and morphological plasticity in polyphagous insect herbivores allow them to exploit diverse host plant species. Geographical differences in resource availability can lead to preferential host exploitation and result in inconsistent host specialization. Biological and molecular data provide insights into specialization and plasticity of such herbivore populations. In agricultural landscapes, Aphis gossypii encounters several crop and non-crop hosts, which exist in temporal and spatial proximity. We investigated the host-specialization of two A. gossypii host-associated populations (HAPs), which were field collected from cotton and squash (cotton-associated population and melon-associated population), and later maintained separately in the greenhouse. The two aphid populations were exposed to seven plant species (cotton, okra, watermelon, squash, cucumber, pigweed, and morning glory), and evaluated for their host utilization plasticity by estimating aphid's fitness parameters (nymphal period, adult period, fecundity, and intrinsic rate of increase). Four phenotypical characters (body length, head capsule width, hind tibia length and cornicle length) were also measured from the resulting 14 different HAP × host plant combinations. Phylogenetic analysis of mitochondrial COI sequences showed no genetic variation between the two HAPs. Fitness parameters indicated a significant variation between the two aphid populations, and the variation was influenced by host plants. The performance of melon-aphids was poor (up to 89% reduction in fecundity) on malvaceous hosts, cotton and okra. However, cotton-aphids performed better on cucurbitaceous hosts, squash and watermelon (up to 66% increased fecundity) compared with the natal host, cotton. Both HAPs were able to reproduce on two weed hosts. Cotton-aphids were smaller than melon-aphids irrespective of their host plants. Results from this study suggest that the two HAPs in the study area do not have strict host

Isolation of recombinant phage antibodies targeting the hemagglutinin cleavage site of highly pathogenic avian influenza virus.

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Jinhua Dong

Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses, which have emerged in poultry and other wildlife worldwide, contain a characteristic multi-basic cleavage site (CS in the hemagglutinin protein (HA. Because this arginine-rich CS is unique among influenza virus subtypes, antibodies against this site have the potential to specifically diagnose pathogenic H5N1. By immunizing mice with the CS peptide and screening a phage display library, we isolated four antibody Fab fragment clones that specifically bind the antigen peptide and several HPAI H5N1 HA proteins in different clades. The soluble Fab fragments expressed in Escherichia coli bound the CS peptide and the H5N1 HA protein with nanomolar affinity. In an immunofluorescence assay, these Fab fragments stained cells infected with HPAI H5N1 but not those infected with a less virulent strain. Lastly, all the Fab clones could detect the CS peptide and H5N1 HA protein by open sandwich ELISA. Thus, these recombinant Fab fragments will be useful novel reagents for the rapid and specific detection of HPAI H5N1 virus.

Evaluation of multiplex assay platforms for detection of influenza hemagglutinin subtype specific antibody responses.

Science.gov (United States)

Li, Zhu-Nan; Weber, Kimberly M; Limmer, Rebecca A; Horne, Bobbi J; Stevens, James; Schwerzmann, Joy; Wrammert, Jens; McCausland, Megan; Phipps, Andrew J; Hancock, Kathy; Jernigan, Daniel B; Levine, Min; Katz, Jacqueline M; Miller, Joseph D

2017-05-01

Influenza hemagglutination inhibition (HI) and virus microneutralization assays (MN) are widely used for seroprevalence studies. However, these assays have limited field portability and are difficult to fully automate for high throughput laboratory testing. To address these issues, three multiplex influenza subtype-specific antibody detection assays were developed using recombinant hemagglutinin antigens in combination with Chembio, Luminex ® , and ForteBio ® platforms. Assay sensitivity, specificity, and subtype cross-reactivity were evaluated using a panel of well characterized human sera. Compared to the traditional HI, assay sensitivity ranged from 87% to 92% and assay specificity in sera collected from unexposed persons ranged from 65% to 100% across the platforms. High assay specificity (86-100%) for A(H5N1) rHA was achieved for sera from exposed or unexposed to hetorosubtype influenza HAs. In contrast, assay specificity for A(H1N1)pdm09 rHA using sera collected from A/Vietnam/1204/2004 (H5N1) vaccinees in 2008 was low (22-30%) in all platforms. Although cross-reactivity against rHA subtype proteins was observed in each assay platform, the correct subtype specific responses were identified 78%-94% of the time when paired samples were available for analysis. These results show that high throughput and portable multiplex assays that incorporate rHA can be used to identify influenza subtype specific infections. Published by Elsevier B.V.

Helminth burden and ecological factors associated with alterations in wild host gastrointestinal microbiota

DEFF Research Database (Denmark)

Newbold, Lindsay K.; Burthe, Sarah J.; Oliver, Anna E.

2017-01-01

Infection by gastrointestinal helminths of humans, livestock and wild animals is common, but the impact of such endoparasites on wild hosts and their gut microbiota represents an important overlooked component of population dynamics. Wild host gut microbiota and endoparasites occupy the same...... to quantify helminth infection in situ. Microbiota from the significantly distinct proventriculus (site of infection), cloacal and faecal gastrointestinal tract microbiomes were characterised using 16S rRNA gene-targeted high-throughput sequencing. We found increasingly strong associations between helminth...... infection and microbiota composition progressing away from the site of infection, observing a pronounced dysbiosis in microbiota when samples were partitioned into high- and low-burden groups. We posit this dysbiosis is predominately explained by helminths inducing an anti-inflammatory environment...

Secretion of human epidermal growth factor (EGF) in autotrophic culture by a recombinant hydrogen-utilizing bacterium, Pseudomonas pseudoflava, carrying broad-host-range EGF secretion vector pKSEGF2.

OpenAIRE

Hayase, N; Ishiyama, A; Niwano, M

1994-01-01

We constructed the broad-host-range human epidermal growth factor (EGF) secretion plasmid pKSEGF2 by inserting the Escherichia coli tac promoter, the signal sequence of Pseudomonas stutzeri amylase, and the synthesized EGF gene into the broad-host-range vector pKT230. E. coli JM109 carrying pKSEGF2 secreted EGF into the periplasm and the culture medium under the control of the tac promoter. Pseudomonas aeruginosa PAO1161 carrying pKSEGF2 and Pseudomonas putida AC10 carrying pKSEGF2 secreted E...

HostPhinder: A Phage Host Prediction Tool

DEFF Research Database (Denmark)

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

2016-01-01

The current dramatic increase of antibiotic resistant bacteria has revitalised the interest in bacteriophages as alternative antibacterial treatment. Meanwhile, the development of bioinformatics methods for analysing genomic data places high-throughput approaches for phage characterization within...... bacterial hosts. HostPhinder is available as an interactive web service [1] and as a stand alone download from the Docker registry [2]....

Trophic Relationships between the Parasitic Plant Species Phelipanche ramosa (L.) and Different Hosts Depending on Host Phenological Stage and Host Growth Rate

Science.gov (United States)

Moreau, Delphine; Gibot-Leclerc, Stéphanie; Girardin, Annette; Pointurier, Olivia; Reibel, Carole; Strbik, Florence; Fernández-Aparicio, Mónica; Colbach, Nathalie

2016-01-01

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%). B. 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 host plant

Ability of a Generalist Seed Beetle to Colonize an Exotic Host: Effects of Host Plant Origin and Oviposition Host.

Science.gov (United States)

Amarillo-Suárez, A; Repizo, A; Robles, J; Diaz, J; Bustamante, S

2017-08-01

The colonization of an exotic species by native herbivores is more likely to occur if that herbivore is a generalist. There is little information on the life-history mechanisms used by native generalist insects to colonize exotic hosts and how these mechanisms are affected by host properties. We examined the ability of the generalist seed beetle Stator limbatus Horn to colonize an exotic species. We compared its host preference, acceptability, performance, and egg size when ovipositing and developing on two native (Pithecellobium dulce (Roxb.) Benth and Senegalia riparia (Kunth)) and one exotic legume species (Leucaena leucocephala (Lam.)). We also analyzed the seed chemistry. We found that females recognize the exotic species as an unfavorable host for larval development and that they delayed oviposition and laid fewer and larger eggs on the exotic species than on the native species. Survivorship on the exotic host was 0%. Additionally, seeds of the native species contain five chemical compounds that are absent in the exotic species, and the exotic species contains three sterols, which are absent in the native legumes. Genetically based differences between beetles adapted to different hosts, plastic responses toward new hosts, and chemical differences among seeds are important in host colonization and recognition of the exotic host. In conclusion, the generalist nature of S. limbatus does not influence its ability to colonize L. leucocephala. Explanations for the colonization of exotic hosts by generalist native species and for the success of invasive species must be complemented with studies measuring local adaptation and plasticity.

Efficiency of vibrational sounding in parasitoid host location depends on substrate density.

Science.gov (United States)

Fischer, S; Samietz, J; Dorn, S

2003-10-01

Parasitoids of concealed hosts have to drill through a substrate with their ovipositor for successful parasitization. Hymenopteran species in this drill-and-sting guild locate immobile pupal hosts by vibrational sounding, i.e., echolocation on solid substrate. Although this host location strategy is assumed to be common among the Orussidae and Ichneumonidae there is no information yet whether it is adapted to characteristics of the host microhabitat. This study examined the effect of substrate density on responsiveness and host location efficiency in two pupal parasitoids, Pimpla turionellae and Xanthopimpla stemmator (Hymenoptera: Ichneumonidae), with different host-niche specialization and corresponding ovipositor morphology. Location and frequency of ovipositor insertions were scored on cylindrical plant stem models of various densities. Substrate density had a significant negative effect on responsiveness, number of ovipositor insertions, and host location precision in both species. The more niche-specific species X. stemmator showed a higher host location precision and insertion activity. We could show that vibrational sounding is obviously adapted to the host microhabitat of the parasitoid species using this host location strategy. We suggest the attenuation of pulses during vibrational sounding as the energetically costly limiting factor for this adaptation.

Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions.

Science.gov (United States)

Duneau, David; Luijckx, Pepijn; Ben-Ami, Frida; Laforsch, Christian; Ebert, Dieter

2011-02-22

Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary cycles. We discuss how different

Resolving the infection process reveals striking differences in the contribution of environment, genetics and phylogeny to host-parasite interactions

Directory of Open Access Journals (Sweden)

Laforsch Christian

2011-02-01

Full Text Available Abstract Background Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Results Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Conclusions Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key

Dual analysis of the murine cytomegalovirus and host cell transcriptomes reveal new aspects of the virus-host cell interface.

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Vanda Juranic Lisnic

Full Text Available Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq. We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus

Radiation and host factors in human thyroid tumors following thymus irradiation

International Nuclear Information System (INIS)

Shore, R.E.; Pasternack, B.S.; Woodard, E.D.; Hempelmann, L.H.

1980-01-01

Thyroid tumor data from the 1971 survey of the Rochester, New York thymus irradiated population are further analyzed to study radiobiological and host factors. The analyses were based on the approx. 2650 irradiated subjects and 4800 sibling controls who had 5 or more years of follow-up. Twenty-four thyroid cancers and 52 thyroid adenomas were found in the irradiated group, and O thyroid cancers and 6 adenomas among the controls. The overall risk estimates were 3.8 thyroid cancers/10 6 persons/yr/rad and 4.5 thyroid adenomas/10 6 persons/yr/rad. The dose-response data (thyroid dose range of 5 to > 1000 rad) for thyroid cancer indicate both a linear and a dose-squared component, but no dose-squared component is evident for thyroid adenomas. At lower total doses (< 400 rad) there was a suggestion that dose fractionation diminished the thyroid cancer response, but a similar fractionation effect was not found for thyroid adenomas. The temporal pattern of tumors suggested an extended plateau of excess tumor production, rather than a wavelike temporal pattern. There was no evidence for an inverse relationship between thyroid radiation dose and thyroid cancer latency. Female and Jewish subjects had a higher risk of radiation-induced thyroid cancer than did their respective counterparts. The additive and multiplicative models of radiation effects were compared with respect to sex differences; neither model provided a superior fit to the data. The tentative nature of the conclusions is stressed because of the relatively small number of thyroid cancers. (author)

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.

Effects of host injury on susceptibility of marine reef fishes to ectoparasitic gnathiid isopods

Science.gov (United States)

Jenkins, William G.; Demopoulos, Amanda W.J.; Sikkel, Paul C.

2018-01-01

The importance of the role that parasites play in ecological communities is becoming increasingly apparent. However much about their impact on hosts and thus populations and communities remains poorly understood. A common observation in wild populations is high variation in levels of parasite infestation among hosts. While high variation could be due to chance encounter, there is increasing evidence to suggest that such patterns are due to a combination of environmental, host, and parasite factors. In order to examine the role of host condition on parasite infection, rates of Gnathia marleyi infestation were compared between experimentally injured and uninjured fish hosts. Experimental injuries were similar to the minor wounds commonly observed in nature. The presence of the injury significantly increased the probability of infestation by gnathiids. However, the level of infestation (i.e., total number of gnathiid parasites) for individual hosts, appeared to be unaffected by the treatment. The results from this study indicate that injuries obtained by fish in nature may carry the additional cost of increased parasite burden along with the costs typically associated with physical injury. These results suggest that host condition may be an important factor in determining the likelihood of infestation by a common coral reef fish ectoparasite, G. marleyi.

Myxoma virus M064 is a novel member of the poxvirus C7L superfamily of host range factors that controls the kinetics of myxomatosis in European rabbits.

Science.gov (United States)

Liu, Jia; Wennier, Sonia; Moussatche, Nissin; Reinhard, Mary; Condit, Richard; McFadden, Grant

2012-05-01

The myxoma virus (MYXV) carries three tandem C7L-like host range genes (M062R, M063R, and M064R). However, despite the fact that the sequences of these three genes are similar, they possess very distinctive functions in vivo. The role of M064 in MYXV pathogenesis was investigated and compared to the roles of M062 and M063. We report that M064 is a virulence factor that contributes to MYXV pathogenesis but lacks the host range properties associated with M062 and M063.

Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions

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Anna Papa

2017-05-01

Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is transmitted to humans by bite of infected ticks or by direct contact with blood or tissues of viremic patients or animals. It causes to humans a severe disease with fatality up to 30%. The current knowledge about the vector-host-CCHFV interactions is very limited due to the high-level containment required for CCHFV studies. Among ticks, Hyalomma spp. are considered the most competent virus vectors. CCHFV evades the tick immune response, and following its replication in the lining of the tick's midgut, it is disseminated by the hemolymph in the salivary glands and reproductive organs. The introduction of salivary gland secretions into the host cells is the major route via which CCHFV enters the host. Following an initial amplification at the site of inoculation, the virus is spread to the target organs. Apoptosis is induced via both intrinsic and extrinsic pathways. Genetic factors and immune status of the host may affect the release of cytokines which play a major role in disease progression and outcome. It is expected that the use of new technology of metabolomics, transcriptomics and proteomics will lead to improved understanding of CCHFV-host interactions and identify potential targets for blocking the CCHFV transmission.

Analyses of Evolutionary Characteristics of the Hemagglutinin-Esterase Gene of Influenza C Virus during a Period of 68 Years Reveals Evolutionary Patterns Different from Influenza A and B Viruses

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Yuki Furuse

2016-11-01

Full Text Available Infections with the influenza C virus causing respiratory symptoms are common, particularly among children. Since isolation and detection of the virus are rarely performed, compared with influenza A and B viruses, the small number of available sequences of the virus makes it difficult to analyze its evolutionary dynamics. Recently, we reported the full genome sequence of 102 strains of the virus. Here, we exploited the data to elucidate the evolutionary characteristics and phylodynamics of the virus compared with influenza A and B viruses. Along with our data, we obtained public sequence data of the hemagglutinin-esterase gene of the virus; the dataset consists of 218 unique sequences of the virus collected from 14 countries between 1947 and 2014. Informatics analyses revealed that (1 multiple lineages have been circulating globally; (2 there have been weak and infrequent selective bottlenecks; (3 the evolutionary rate is low because of weak positive selection and a low capability to induce mutations; and (4 there is no significant positive selection although a few mutations affecting its antigenicity have been induced. The unique evolutionary dynamics of the influenza C virus must be shaped by multiple factors, including virological, immunological, and epidemiological characteristics.

Host genetic variation impacts microbiome composition across human body sites.

Science.gov (United States)

Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G

2015-09-15

The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis : A Systematic Review

NARCIS (Netherlands)

Kroesen, Vera M.; Gröschel, Matthias I.; Martinson, Neil; Zumla, Alimuddin; Maeurer, Markus; van der Werf, Tjip S.; Vilaplana, Cristina

2017-01-01

Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs), in contrast, target host factors to mitigate disease severity. In

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.

Differential expression and interaction of host factors augment HIV-1 gene expression in neonatal mononuclear cells

International Nuclear Information System (INIS)

Sundaravaradan, Vasudha; Mehta, Roshni; Harris, David T.; Zack, Jerome A.; Ahmad, Nafees

2010-01-01

We have previously shown a higher level of HIV-1 replication and gene expression in neonatal (cord) blood mononuclear cells (CBMC) compared with adult blood cells (PBMC), which could be due to differential expression of host factors. We performed the gene expression profile of CBMC and PBMC and found that 8013 genes were expressed at higher levels in CBMC than PBMC and 8028 genes in PBMC than CBMC, including 1181 and 1414 genes upregulated after HIV-1 infection in CBMC and PBMC, respectively. Several transcription factors (NF-κB, E2F, HAT-1, TFIIE, Cdk9, Cyclin T1), signal transducers (STAT3, STAT5A) and cytokines (IL-1β, IL-6, IL-10) were upregulated in CBMC than PBMC, which are known to influence HIV-1 replication. In addition, a repressor of HIV-1 transcription, YY1, was down regulated in CBMC than PBMC and several matrix metalloproteinase (MMP-7, -12, -14) were significantly upregulated in HIV-1 infected CBMC than PBMC. Furthermore, we show that CBMC nuclear extracts interacted with a higher extent to HIV-1 LTR cis-acting sequences, including NF-κB, NFAT, AP1 and NF-IL6 compared with PBMC nuclear extracts and retroviral based short hairpin RNA (shRNA) for STAT3 and IL-6 down regulated their own and HIV-1 gene expression, signifying that these factors influenced differential HIV-1 gene expression in CBMC than PBMC.

Effects of host species and population density on Anoplophora glabripennis flight propensity

Science.gov (United States)

Joseph A. Francese; David R. Lance; Baode Wang; Zhichun Xu; Alan J. Sawyer; Victor C. Mastro

2007-01-01

Anoplophora glabripennis Motschulsky (Coleoptera: Cerambycidae), the Asian longhorned beetle (ALB) is a pest of hardwoods in its native range of China. While the host range of this pest has been studied extensively, its mechanisms for host selection are still unknown. Our goal was to study the factors influencing movement and orientation of adult ALB...

Perspectives on the Trypanosoma cruzi–host cell receptor interactions

Science.gov (United States)

Villalta, Fernando; Scharfstein, Julio; Ashton, Anthony W.; Tyler, Kevin M.; Guan, Fangxia; Mukherjee, Shankar; Lima, Maria F.; Alvarez, Sandra; Weiss, Louis M.; Huang, Huan; Machado, Fabiana S.

2009-01-01

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets. PMID:19283409

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

NARCIS (Netherlands)

Burger, J.M.S.; Komany, A.; Lenteren, van 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

The Effect of Host-Plant Phylogenetic Isolation on Species Richness, Composition and Specialization of Insect Herbivores: A Comparison between Native and Exotic Hosts.

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Julio Miguel Grandez-Rios

Full Text Available Understanding the drivers of plant-insect interactions is still a key issue in terrestrial ecology. Here, we used 30 well-defined plant-herbivore assemblages to assess the effects of host plant phylogenetic isolation and origin (native vs. exotic on the species richness, composition and specialization of the insect herbivore fauna on co-occurring plant species. We also tested for differences in such effects between assemblages composed exclusively of exophagous and endophagous herbivores. We found a consistent negative effect of the phylogenetic isolation of host plants on the richness, similarity and specialization of their insect herbivore faunas. Notably, except for Jaccard dissimilarity, the effect of phylogenetic isolation on the insect herbivore faunas did not vary between native and exotic plants. Our findings show that the phylogenetic isolation of host plants is a key factor that influences the richness, composition and specialization of their local herbivore faunas, regardless of the host plant origin.

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

Host Gene Expression Analysis in Sri Lankan Melioidosis Patients

Science.gov (United States)

2017-06-19

CCL5 Chemokine (C-C motif) ligand 5 /RANTES. IFNγ Interferon gamma TNFα Tumor necrosis factor alpha HMGB1 High mobility group box 1 protein /high...aim of this study was to analyze gene expression levels of human host factors in melioidosis patients and establish useful correlation with disease...PBMC’s) of study subjects. Gene expression profiles of 25 gene targets including 19 immune response genes and 6 epigenetic factors were analyzed by

Natal Host Plants Can Alter Herbivore Competition.

Science.gov (United States)

Pan, Huipeng; Preisser, Evan L; Su, Qi; Jiao, Xiaoguo; Xie, Wen; Wang, Shaoli; Wu, Qingjun; Zhang, Youjun

2016-01-01

Interspecific competition between herbivores is widely recognized as an important determinant of community structure. Although researchers have identified a number of factors capable of altering competitive interactions, few studies have addressed the influence of neighboring plant species. If adaptation to/ epigenetic effects of an herbivore's natal host plant alter its performance on other host plants, then interspecific herbivore interactions may play out differently in heterogeneous and homogenous plant communities. We tested wether the natal host plant of a whitefly population affected interactions between the Middle-east Asia Minor 1 (MEAM1) and Mediterranean (MED) cryptic species of the whitefly Bemisia tabaci by rearing the offspring of a cabbage-derived MEAM1 population and a poinsettia-derived MED population together on three different host plants: cotton, poinsettia, and cabbage. We found that MED dominated on poinsettia and that MEAM1 dominated on cabbage, results consistent with previous research. MED also dominated when reared with MEAM1 on cotton, however, a result at odds with multiple otherwise-similar studies that reared both species on the same natal plant. Our work provides evidence that natal plants affect competitive interactions on another plant species, and highlights the potential importance of neighboring plant species on herbivore community composition in agricultral systems.

Insecticidal activity of the metalloprotease AprA occurs through suppression of host cellular and humoral immunity.

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Lee, Seung Ah; Jang, Seong Han; Kim, Byung Hyun; Shibata, Toshio; Yoo, Jinwook; Jung, Yunjin; Kawabata, Shun-Ichiro; Lee, Bok Luel

2018-04-01

The biochemical characterization of virulence factors from entomopathogenic bacteria is important to understand entomopathogen-insect molecular interactions. Pseudomonas entomophila is a typical entomopathogenic bacterium that harbors virulence factors against several insects. However, the molecular actions of these factors against host innate immune responses are not clearly elucidated. In this study, we observed that bean bugs (Riptortus pedestris) that were injected with P. entomophila were highly susceptible to this bacterium. To determine how P. entomophila counteracts the host innate immunity to survive within the insect, we purified a highly enriched protein with potential host insect-killing activity from the culture supernatant of P. entomophila. Then, a 45-kDa protein was purified to homogeneity and identified as AprA which is an alkaline zinc metalloprotease of the genus Pseudomonas by liquid chromatography mass spectrometry (LC-MS). Purified AprA showed a pronounced killing effect against host insects and suppressed both host cellular and humoral innate immunity. Furthermore, to show that AprA is an important insecticidal protein of P. entomophila, we used an aprA-deficient P. entomophila mutant strain (ΔaprA). When ΔaprA mutant cells were injected to host insects, this mutant exhibited extremely attenuated virulence. In addition, the cytotoxicity against host hemocytes and the antimicrobial peptide-degrading ability of the ΔaprA mutant were greatly decreased. These findings suggest that AprA functions as an important insecticidal protein of P. entomophila via suppression of host cellular and humoral innate immune responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Two different strategies of host manipulation allow parasites to persist in intermediate-definitive host systems

NARCIS (Netherlands)

Vries, de L.J.; Langevelde, van F.

2018-01-01

Trophically transmitted parasites start their development in an intermediate host, before they finish the development in their definitive host when the definitive host preys on the intermediate host. In intermediate-definitive host systems, two strategies of host manipulation have been evolved:

Chemical similarity between historical and novel host plants promotes range and host expansion of the mountain pine beetle in a naïve host ecosystem.

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Erbilgin, Nadir; Ma, Cary; Whitehouse, Caroline; Shan, Bin; Najar, Ahmed; Evenden, Maya

2014-02-01

Host plant secondary chemistry can have cascading impacts on host and range expansion of herbivorous insect populations. We investigated the role of host secondary compounds on pheromone production by the mountain pine beetle (Dendroctonus ponderosae) (MPB) and beetle attraction in response to a historical (lodgepole pine, Pinus contorta var. latifolia) and a novel (jack pine, Pinus banksiana) hosts, as pheromones regulate the host colonization process. Beetles emit the same pheromones from both hosts, but more trans-verbenol, the primary aggregation pheromone, was emitted by female beetles on the novel host. The phloem of the novel host contains more α-pinene, a secondary compound that is the precursor for trans-verbenol production in beetle, than the historical host. Beetle-induced emission of 3-carene, another secondary compound found in both hosts, was also higher from the novel host. Field tests showed that the addition of 3-carene to the pheromone mixture mimicking the aggregation pheromones produced from the two host species increased beetle capture. We conclude that chemical similarity between historical and novel hosts has facilitated host expansion of MPB in jack pine forests through the exploitation of common host secondary compounds for pheromone production and aggregation on the hosts. Furthermore, broods emerging from the novel host were larger in terms of body size. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Suppressor T-cell factor(s) display an altered pattern of Igh (immunoglobulin heavy chain locus) genetic restriction when developed in an Igh-congeneic host

International Nuclear Information System (INIS)

HayGlass, K.T.; Naides, S.J.; Benacerraf, B.; Sy, M.S.

1985-01-01

Suppressor T cell factor(s) (TsF 1 ) inhibit the in vivo priming of azobenzenearsonate-specific cytotoxic T-cell responses. The activity of TsF 1 is restricted by genes linked to Igh-1 allotypic markers. TsF 1 obtained from B6.Igh-1/sup n/ mice was unable to suppress the immune response in B6.Igh-1/sup b/ mice and vice versa. However, TsF 1 prepared from B6.Igh-1/sup n/ T cells parked in an Igh-congeneic B6.Igh-1/sup b/ environment displays an additional restriction specificity of the host. Thus, TsF 1 prepared from these Igh-chimeric mice suppressed immune responses in both B6.Igh-1/sup n/ (donor) and B6.Igh-1/sup b/ (recipient) mice but not in mice of the unrelated strain BALB/c.Igh-1/sup a/. The results indicate that the establishment of the suppressor T-cell repertoire is dependent not only upon the genetic background of the individual T cell but also upon the influence of Igh-linked determinants present when T-cell clones are selected during the response

Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants

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Xueyong Zhu

2015-11-01

Full Text Available Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA mutants from ferret-transmissible H5N1 viruses of A/Vietnam/1203/2004 and A/Indonesia/5/2005 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6-linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3-linked sialosides. Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogs reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses.

Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

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Costa Luciano Bello

2002-01-01

Full Text Available There is increasing interest in the identification of factors associated with liver disease progression in patients infected with hepatitis C virus (HCV. We assessed host-related factors associated with a histologically advanced stage of this disease and determined the rate of liver fibrosis progression in HCV-infected patients. We included patients submitted to liver biopsy, who were anti-HCV and HCV RNA positive, who showed a parenteral risk factor (blood transfusion or intravenous drug use, and who gave information about alcohol consumption.Patients were divided into two groups for analysis: group 1 - grades 0 to 2; group 2 - grades 3 to 4. The groups were compared in terms of sex, age at the time of infection, estimated duration of infection and alcoholism. The rate of fibrosis progression (index of fibrosis was determined based on the relationship between disease stage and duration of infection (years. Logistic regression analysis revealed that age at the time of infection (P or = 40 years (median = 0.47. The main factors associated with a more rapid fibrosis progression were age at the time of infection and the estimated duration of infection. Patients who acquired HCV after 40 years of age showed a higher rate of fibrosis progression.

Acute radiation syndrome (ARS – treatment of the reduced host defense

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Heslet L

2012-01-01

Full Text Available Lars Heslet1, Christiane Bay2, Steen Nepper-Christensen31Serendex ApS, Gentofte; 2University of Copenhagen, Medical Faculty, Copenhagen; 3Department of Head and Neck Surgery, Otorhinolaryngology, Køge University Hospital, Køge, DenmarkBackground: The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS. The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF] in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes.Methods: Review of the current literature.Results: The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage’s important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS.Recommendation: Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least ~2 Gy by prompt dosing of 250–400 µg GM-CSF/m2 or 5 µg/kg G-CSF administered systemically and concomitant inhalation of

CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy.

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Chen, Shuliang; Yu, Xiao; Guo, Deyin

2018-01-16

Currently, a new gene editing tool-the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system-is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy.

Influenza A Virus Hemagglutinin is Required for the Assembly of Viral Components Including Bundled vRNPs at the Lipid Raft

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Naoki Takizawa

2016-09-01

Full Text Available The influenza glycoproteins, hemagglutinin (HA and neuraminidase (NA, which are associated with the lipid raft, have the potential to initiate virion budding. However, the role of these viral proteins in infectious virion assembly is still unclear. In addition, it is not known how the viral ribonucleoprotein complex (vRNP is tethered to the budding site. Here, we show that HA is necessary for the efficient progeny virion production and vRNP packaging in the virion. We also found that the level of HA does not affect the bundling of the eight vRNP segments, despite reduced virion production. Detergent solubilization and a subsequent membrane flotation analysis indicated that the accumulation of nucleoprotein, viral polymerases, NA, and matrix protein 1 (M1 in the lipid raft fraction was delayed without HA. Based on our results, we inferred that HA plays a role in the accumulation of viral components, including bundled vRNPs, at the lipid raft.

Influenza A Virus Hemagglutinin is Required for the Assembly of Viral Components Including Bundled vRNPs at the Lipid Raft.

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Takizawa, Naoki; Momose, Fumitaka; Morikawa, Yuko; Nomoto, Akio

2016-09-10

The influenza glycoproteins, hemagglutinin (HA) and neuraminidase (NA), which are associated with the lipid raft, have the potential to initiate virion budding. However, the role of these viral proteins in infectious virion assembly is still unclear. In addition, it is not known how the viral ribonucleoprotein complex (vRNP) is tethered to the budding site. Here, we show that HA is necessary for the efficient progeny virion production and vRNP packaging in the virion. We also found that the level of HA does not affect the bundling of the eight vRNP segments, despite reduced virion production. Detergent solubilization and a subsequent membrane flotation analysis indicated that the accumulation of nucleoprotein, viral polymerases, NA, and matrix protein 1 (M1) in the lipid raft fraction was delayed without HA. Based on our results, we inferred that HA plays a role in the accumulation of viral components, including bundled vRNPs, at the lipid raft.

Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin.

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Carbone, V; Kim, H; Huang, J X; Baker, M A; Ong, C; Cooper, M A; Li, J; Rockman, S; Velkov, T

2013-01-01

Selectivity of α2,6-linked human-like receptors by B hemagglutinin (HA) is yet to be fully understood. This study integrates binding data with structure-recognition models to examine the impact of regional-specific sequence variations within the receptor-binding pocket on selectivity and structure activity relationships (SAR). The receptor-binding selectivity of influenza B HAs corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was examined using surface plasmon resonance, solid-phase ELISA and gel-capture assays. Our SAR data showed that the presence of asialyl sugar units is the main determinant of receptor preference of α2,6 versus α2,3 receptor binding. Changes to the type of sialyl-glycan linkage present on receptors exhibit only a minor effect upon binding affinity. Homology-based structural models revealed that structural properties within the HA pocket, such as a glyco-conjugate at Asn194 on the 190-helix, sterically interfere with binding to avian receptor analogs by blocking the exit path of the asialyl sugars. Similarly, naturally occurring substitutions in the C-terminal region of the 190-helix and near the N-terminal end of the 140-loop narrows the horizontal borders of the binding pocket, which restricts access of the avian receptor analog LSTa. This study helps bridge the gap between ligand structure and receptor recognition for influenza B HA; and provides a consensus SAR model for the binding of human and avian receptor analogs to influenza B HA.

Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection

NARCIS (Netherlands)

Rodrigues, Cristina D.; Hannus, Michael; Prudencio, Miguel; Martin, Cecilie; Goncalves, Ligia A.; Portugal, Silvia; Epiphanio, Sabrina; Akinc, Akin; Hadwiger, Philipp; Jahn-Hofmann, Kerstin; Roehl, Ingo; van Gemert, Geert-Jan; Franetich, Jean-Francois; Luty, Adrian J. F.; Sauerwein, Robert; Mazier, Dominique; Koteliansky, Victor; Vornlocher, Hans-Peter; Echeverri, Christophe J.; Mota, Maria M.

2008-01-01

An obligatory step of malaria parasite infection is Plasmodium sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to Plasmodium liver infection. By using RNA interference to screen lipoprotein-related host factors, we show here that the class B, type I

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication.

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Griffiths, Samantha J; Koegl, Manfred; Boutell, Chris; Zenner, Helen L; Crump, Colin M; Pica, Francesca; Gonzalez, Orland; Friedel, Caroline C; Barry, Gerald; Martin, Kim; Craigon, Marie H; Chen, Rui; Kaza, Lakshmi N; Fossum, Even; Fazakerley, John K; Efstathiou, Stacey; Volpi, Antonio; Zimmer, Ralf; Ghazal, Peter; Haas, Jürgen

2013-01-01

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication.

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Samantha J Griffiths

Full Text Available Herpes simplex virus type 1 (HSV-1 is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi screen with a druggable genome small interfering RNA (siRNA library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome

Determinants of the Sympatric Host-Pathogen Relationship in Tuberculosis

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David, Susana; Mateus, A. R. A.; Duarte, Elsa L.; Albuquerque, José; Portugal, Clara; Sancho, Luísa; Lavinha, João; Gonçalves, Guilherme

2015-01-01

Major contributions from pathogen genome analysis and host genetics have equated the possibility of Mycobacterium tuberculosis co-evolution with its human host leading to more stable sympatric host–pathogen relationships. However, the attribution to either sympatric or allopatric categories depends on the resolution or grain of genotypic characterization. We explored the influence on the sympatric host-pathogen relationship of clinical (HIV infection and multidrug-resistant tuberculosis [MDRTB]) and demographic (gender and age) factors in regards to the genotypic grain by using spacer oligonucleotide typing (spoligotyping) for classification of M. tuberculosis strains within the Euro-American lineage. We analyzed a total of 547 tuberculosis (TB) cases, from six year consecutive sampling in a setting with high TB-HIV coinfection (32.0%). Of these, 62.0% were caused by major circulating pathogen genotypes. The sympatric relationship was defined according to spoligotype in comparison to the international spoligotype database SpolDB4. While no significant association with Euro-American lineage was observed with any of the factors analyzed, increasing the resolution with spoligotyping evidenced a significant association of MDRTB with sympatric strains, regardless of the HIV status. Furthermore, distribution curves of the prevalence of sympatric and allopatric TB in relation to patients’ age showed an accentuation of the relevance of the age of onset in the allopatric relationship, as reflected in the trimodal distribution. On the contrary, sympatric TB was characterized by the tendency towards a typical (standard) distribution curve. Our results suggest that within the Euro-American lineage a greater degree of genotyping fine-tuning is necessary in modeling the biological processes behind the host-pathogen interplay. Furthermore, prevalence distribution of sympatric TB to age was suggestive of host genetic determinisms driven by more common variants. PMID:26529092

Co-extinction in a host-parasite network: identifying key hosts for network stability.

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Dallas, Tad; Cornelius, Emily

2015-08-17

Parasites comprise a substantial portion of total biodiversity. Ultimately, this means that host extinction could result in many secondary extinctions of obligate parasites and potentially alter host-parasite network structure. Here, we examined a highly resolved fish-parasite network to determine key hosts responsible for maintaining parasite diversity and network structure (quantified here as nestedness and modularity). We evaluated four possible host extinction orders and compared the resulting co-extinction dynamics to random extinction simulations; including host removal based on estimated extinction risk, parasite species richness and host level contributions to nestedness and modularity. We found that all extinction orders, except the one based on realistic extinction risk, resulted in faster declines in parasite diversity and network structure relative to random biodiversity loss. Further, we determined species-level contributions to network structure were best predicted by parasite species richness and host family. Taken together, we demonstrate that a small proportion of hosts contribute substantially to network structure and that removal of these hosts results in rapid declines in parasite diversity and network structure. As network stability can potentially be inferred through measures of network structure, our findings may provide insight into species traits that confer stability.

MVA recombinants expressing the fusion and hemagglutinin genes of PPRV protects goats against virulent challenge.

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Chandran, Dev; Reddy, Kolli Bhaktavatsala; Vijayan, Shahana Pallichera; Sugumar, Parthasarthy; Rani, Gudavalli Sudha; Kumar, Ponsekaran Santha; Rajendra, Lingala; Srinivasan, Villuppanoor Alwar

2010-09-01

Peste des Petits Ruminants (PPR) is a highly contagious animal disease caused by the Peste des Petits Ruminants virus (PPRV) belonging to the genus morbillivirus and family Paramyxoviridae. The disease results in high morbidity and mortality in goats, sheep and in some small wild ruminants. The presence of large number of small ruminants reared in endemic areas makes PPR a notorious disease threatening the livelihood of poor farmers. Conventional vaccination using a live, attenuated vaccine gives adequate protection but cannot be used in case of eradication of the disease due to difficulty in differentiation of infected animals from the vaccinated ones.In the present study, we constructed two recombinant viruses using attenuated Modified Vaccinia virus Ankara virus (MVA) namely MVA-F and MVA-H expressing the full length PPRV fusion (F) and hemagglutinin (H) glycoproteins, respectively. Goats were vaccinated intramuscularly with 105 plaque forming units (PFU) each of the recombinant viruses and a live attenuated vaccine (RAKSHA PPR) and challenged 4 months later with PPRV challenge virus (10(3) goat LD(50)). All goats were completely protected from the clinical disease. This study gave an indication that mass vaccination of small ruminants with either of the above or both recombinant inexpensive virus vaccines could help in possible eradication of PPRV from endemic countries like India and subsequent seromonitoring of the disease for differentiation of infected animals from vaccinated ones.

A novel eight amino acid insertion contributes to the hemagglutinin cleavability and the virulence of a highly pathogenic avian influenza A (H7N3) virus in mice

International Nuclear Information System (INIS)

Sun, Xiangjie; Belser, Jessica A.; Tumpey, Terrence M.

2016-01-01

In 2012, an avian influenza A H7N3 (A/Mexico/InDRE7218/2012; Mx/7218) virus was responsible for two confirmed cases of human infection and led to the death or culling of more than 22 million chickens in Jalisco, Mexico. Interestingly, this virus acquired an 8-amino acid (aa)-insertion (..PENPK-DRKSRHRR-TR/GLF) near the hemagglutinin (HA) cleavage site by nonhomologous recombination with host rRNA. It remains unclear which specific residues at the cleavage site contribute to the virulence of H7N3 viruses in mammals. Using loss-of-function approaches, we generated a series of cleavage site mutant viruses by reverse genetics and characterized the viruses in vitro and in vivo. We found that the 8-aa insertion and the arginine at position P4 of the Mx/7218 HA cleavage site are essential for intracellular HA cleavage in 293T cells, but have no effect on the pH of membrane fusion. However, we identified a role for the histidine residue at P5 position in viral fusion pH. In mice, the 8-aa insertion is required for Mx/7218 virus virulence; however, the basic residues upstream of the P4 position are dispensable for virulence. Overall, our study provides the first line of evidence that the insertion in the Mx/7218 virus HA cleavage site confers its intracellular cleavability, and consequently contributes to enhanced virulence in mice. - Highlights: • An avian influenza H7N3 virus acquired a unique 8-amino acid (aa) insertion. • The role of specific basic residues in the HA insertion in viral pathogenesis was determined. • In mice, the 8-aa insertion is required for H7N3 virus virulence. • The R residue at position P4 is essential for HA intracellular cleavage and virus virulence.

A novel eight amino acid insertion contributes to the hemagglutinin cleavability and the virulence of a highly pathogenic avian influenza A (H7N3) virus in mice

Energy Technology Data Exchange (ETDEWEB)

Sun, Xiangjie; Belser, Jessica A.; Tumpey, Terrence M., E-mail: tft9@cdc.gov

2016-01-15

In 2012, an avian influenza A H7N3 (A/Mexico/InDRE7218/2012; Mx/7218) virus was responsible for two confirmed cases of human infection and led to the death or culling of more than 22 million chickens in Jalisco, Mexico. Interestingly, this virus acquired an 8-amino acid (aa)-insertion (..PENPK-DRKSRHRR-TR/GLF) near the hemagglutinin (HA) cleavage site by nonhomologous recombination with host rRNA. It remains unclear which specific residues at the cleavage site contribute to the virulence of H7N3 viruses in mammals. Using loss-of-function approaches, we generated a series of cleavage site mutant viruses by reverse genetics and characterized the viruses in vitro and in vivo. We found that the 8-aa insertion and the arginine at position P4 of the Mx/7218 HA cleavage site are essential for intracellular HA cleavage in 293T cells, but have no effect on the pH of membrane fusion. However, we identified a role for the histidine residue at P5 position in viral fusion pH. In mice, the 8-aa insertion is required for Mx/7218 virus virulence; however, the basic residues upstream of the P4 position are dispensable for virulence. Overall, our study provides the first line of evidence that the insertion in the Mx/7218 virus HA cleavage site confers its intracellular cleavability, and consequently contributes to enhanced virulence in mice. - Highlights: • An avian influenza H7N3 virus acquired a unique 8-amino acid (aa) insertion. • The role of specific basic residues in the HA insertion in viral pathogenesis was determined. • In mice, the 8-aa insertion is required for H7N3 virus virulence. • The R residue at position P4 is essential for HA intracellular cleavage and virus virulence.

The effects of host-feeding on stability of discrete-time host-parasitoid population dynamic models.

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Emerick, Brooks; Singh, Abhyudai

2016-02-01

Discrete-time models are the traditional approach for capturing population dynamics of a host-parasitoid system. Recent work has introduced a semi-discrete framework for obtaining model update functions that connect host-parasitoid population levels from year-to-year. In particular, this framework uses differential equations to describe the host-parasitoid interaction during the time of year when they come in contact, allowing specific behaviors to be mechanistically incorporated. We use the semi-discrete approach to study the effects of host-feeding, which occurs when a parasitoid consumes a potential host larva without ovipositing. We find that host-feeding by itself cannot stabilize the system, and both populations exhibit behavior similar to the Nicholson-Bailey model. However, when combined with stabilizing mechanisms such as density-dependent host mortality, host-feeding contracts the region of parameter space that allows for a stable host-parasitoid equilibrium. In contrast, when combined with a density-dependent parasitoid attack rate, host-feeding expands the non-zero equilibrium stability region. Our results show that host-feeding causes inefficiency in the parasitoid population, which yields a higher population of hosts per generation. This suggests that host-feeding may have limited long-term impact in terms of suppressing host levels for biological control applications. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of joining sites of a viral histone H4 on host insect chromosomes.

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Sunil Kumar

Full Text Available A viral histone H4 (CpBV-H4 is encoded in a polydnavirus, Cotesia plutellae bracovirus (CpBV. It plays a crucial role in parasitism of an endoparasitoid wasp, C. plutellae, against diamondback moth, Plutella xylostella, by altering host gene expression in an epigenetic mode by its N-terminal tail after joining host nucleosomes. Comparative transcriptomic analysis between parasitized and nonparasitized P. xylostella by RNA-Seq indicated that 1,858 genes were altered at more than two folds in expression levels at late parasitic stage, including 877 up-regulated genes and 981 down-regulated genes. Among parasitic factors altering host gene expression, CpBV-H4 alone explained 16.3% of these expressional changes. To characterize the joining sites of CpBV-H4 on host chromosomes, ChIP-Seq (chromatin immunoprecipitation followed by deep sequencing was applied to chromatins extracted from parasitized larvae. It identified specific 538 ChIP targets. Joining sites were rich (60.2% in AT sequence. Almost 40% of ChIP targets included short nucleotide repeat sequences presumably recognizable by transcriptional factors and chromatin remodeling factors. To further validate these CpBV-H4 targets, CpBV-H4 was transiently expressed in nonparasitized host at late larval stage and subjected to ChIP-Seq. Two kinds of ChIP-Seqs shared 51 core joining sites. Common targets were close (within 1 kb to genes regulated at expression levels by CpBV-H4. However, other host genes not close to CpBV-H4 joining sites were also regulated by CpBV-H4. These results indicate that CpBV-H4 joins specific chromatin regions of P. xylostella and controls about one sixth of the total host genes that were regulated by C. plutellae parasitism in an epigenetic mode.

Host density and competency determine the effects of host diversity on trematode parasite infection.

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Jeremy M Wojdak

Full Text Available Variation in host species composition can dramatically alter parasite transmission in natural communities. Whether diverse host communities dilute or amplify parasite transmission is thought to depend critically on species traits, particularly on how hosts affect each other's densities, and their relative competency as hosts. Here we studied a community of potential hosts and/or decoys (i.e. non-competent hosts for two trematode parasite species, Echinostoma trivolvis and Ribeiroia ondatrae, which commonly infect wildlife across North America. We manipulated the density of a focal host (green frog tadpoles, Rana clamitans, in concert with manipulating the diversity of alternative species, to simulate communities where alternative species either (1 replace the focal host species so that the total number of individuals remains constant (substitution or (2 add to total host density (addition. For E. trivolvis, we found that total parasite transmission remained roughly equal (or perhaps decreased slightly when alternative species replaced focal host individuals, but parasite transmission was higher when alternative species were added to a community without replacing focal host individuals. Given the alternative species were roughly equal in competency, these results are consistent with current theory. Remarkably, both total tadpole and per-capita tadpole infection intensity by E. trivolvis increased with increasing intraspecific host density. For R. ondatrae, alternative species did not function as effective decoys or hosts for parasite infective stages, and the diversity and density treatments did not produce clear changes in parasite transmission, although high tank to tank variation in R. ondatrae infection could have obscured patterns.

Fungal-host diversity among mycoheterotrophic plants increases proportionally to their fungal-host overlap.

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Gomes, Sofia I F; Merckx, Vincent S F T; Saavedra, Serguei

2017-05-01

The vast majority of plants obtain an important proportion of vital resources from soil through mycorrhizal fungi. Generally, this happens in exchange of photosynthetically fixed carbon, but occasionally the interaction is mycoheterotrophic, and plants obtain carbon from mycorrhizal fungi. This process results in an antagonistic interaction between mycoheterotrophic plants and their fungal hosts. Importantly, the fungal-host diversity available for plants is restricted as mycoheterotrophic interactions often involve narrow lineages of fungal hosts. Unfortunately, little is known whether fungal-host diversity may be additionally modulated by plant-plant interactions through shared hosts. Yet, this may have important implications for plant competition and coexistence. Here, we use DNA sequencing data to investigate the interaction patterns between mycoheterotrophic plants and arbuscular mycorrhizal fungi. We find no phylogenetic signal on the number of fungal hosts nor on the fungal hosts shared among mycoheterotrophic plants. However, we observe a potential trend toward increased phylogenetic diversity of fungal hosts among mycoheterotrophic plants with increasing overlap in their fungal hosts. While these patterns remain for groups of plants regardless of location, we do find higher levels of overlap and diversity among plants from the same location. These findings suggest that species coexistence cannot be fully understood without attention to the two sides of ecological interactions.

Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways

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Peter Wimmer

2015-08-01

Full Text Available Posttranslational modifications (PTMs of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub and small ubiquitin-like modifier (SUMO moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways.

Local host specialization, host-switching, and dispersal shape the regional distributions of avian haemosporidian parasites.

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Ellis, Vincenzo A; Collins, Michael D; Medeiros, Matthew C I; Sari, Eloisa H R; Coffey, Elyse D; Dickerson, Rebecca C; Lugarini, Camile; Stratford, Jeffrey A; Henry, Donata R; Merrill, Loren; Matthews, Alix E; Hanson, Alison A; Roberts, Jackson R; Joyce, Michael; Kunkel, Melanie R; Ricklefs, Robert E

2015-09-08

The drivers of regional parasite distributions are poorly understood, especially in comparison with those of free-living species. For vector-transmitted parasites, in particular, distributions might be influenced by host-switching and by parasite dispersal with primary hosts and vectors. We surveyed haemosporidian blood parasites (Plasmodium and Haemoproteus) of small land birds in eastern North America to characterize a regional parasite community. Distributions of parasite populations generally reflected distributions of their hosts across the region. However, when the interdependence between hosts and parasites was controlled statistically, local host assemblages were related to regional climatic gradients, but parasite assemblages were not. Moreover, because parasite assemblage similarity does not decrease with distance when controlling for host assemblages and climate, parasites evidently disperse readily within the distributions of their hosts. The degree of specialization on hosts varied in some parasite lineages over short periods and small geographic distances independently of the diversity of available hosts and potentially competing parasite lineages. Nonrandom spatial turnover was apparent in parasite lineages infecting one host species that was well-sampled within a single year across its range, plausibly reflecting localized adaptations of hosts and parasites. Overall, populations of avian hosts generally determine the geographic distributions of haemosporidian parasites. However, parasites are not dispersal-limited within their host distributions, and they may switch hosts readily.

Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.

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Hauser, Kurt F; Knapp, Pamela E

2014-01-01

Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individuals to HIV and to drug abuse can vary tremendously. Host-genetic variability is important in determining viral tropism, neuropathogenesis, drug responses, and addictive behavior. However, genetic differences alone cannot account for individual variability in the brain "connectome." Environment and experience are critical determinants in the evolution of synaptic circuitry throughout life. Neurons and glia both exercise control over determinants of synaptic plasticity that are disrupted by HIV and drug abuse. Perivascular macrophages, microglia, and to a lesser extent astroglia can harbor the infection. Uninfected bystanders, especially astroglia, propagate and amplify inflammatory signals. Drug abuse by itself derails neuronal and glial function, and the outcome of chronic exposure is maladaptive plasticity. The negative consequences of coexposure to HIV and drug abuse are determined by numerous factors including genetics, sex, age, and multidrug exposure. Glia and some neurons are generated throughout life, and their progenitors appear to be targets of HIV and opiates/psychostimulants. The chronic nature of HIV and drug abuse appears to result in sustained alterations in the maturation and fate of neural progenitors, which may affect the balance of glial populations within multiple brain regions. © 2014 Elsevier Inc. All rights reserved.

Cattle Tick Rhipicephalus microplus-Host Interface: A Review of Resistant and Susceptible Host Responses

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Ala E. Tabor

2017-12-01

Full Text Available Ticks are able to transmit tick-borne infectious agents to vertebrate hosts which cause major constraints to public and livestock health. The costs associated with mortality, relapse, treatments, and decreased production yields are economically significant. Ticks adapted to a hematophagous existence after the vertebrate hemostatic system evolved into a multi-layered defense system against foreign invasion (pathogens and ectoparasites, blood loss, and immune responses. Subsequently, ticks evolved by developing an ability to suppress the vertebrate host immune system with a devastating impact particularly for exotic and crossbred cattle. Host genetics defines the immune responsiveness against ticks and tick-borne pathogens. To gain an insight into the naturally acquired resistant and susceptible cattle breed against ticks, studies have been conducted comparing the incidence of tick infestation on bovine hosts from divergent genetic backgrounds. It is well-documented that purebred and crossbred Bos taurus indicus cattle are more resistant to ticks and tick-borne pathogens compared to purebred European Bos taurus taurus cattle. Genetic studies identifying Quantitative Trait Loci markers using microsatellites and SNPs have been inconsistent with very low percentages relating phenotypic variation with tick infestation. Several skin gene expression and immunological studies have been undertaken using different breeds, different samples (peripheral blood, skin with tick feeding, infestation protocols and geographic environments. Susceptible breeds were commonly found to be associated with the increased expression of toll like receptors, MHC Class II, calcium binding proteins, and complement factors with an increased presence of neutrophils in the skin following tick feeding. Resistant breeds had higher levels of T cells present in the skin prior to tick infestation and thus seem to respond to ticks more efficiently. The skin of resistant breeds also

On the importance of macroeconomic factors for the foreign student’s decision to stay in the host country

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Vasiljeva, Kristine

The paper tests empirically whether the macroeconomic variables suggested by migration theories have a significant impact on the foreign student’s decision to stay in their host country. The analysis is based on the combination of country level variables and individual register data. The mean...... labour income difference between the home and the host countries significantly negatively affects the student’s probability of staying in the host country. The differences in the unemployment rates, welfare benefits, business cycles do not affect the probability of staying. The more hierarchical society...

Single Dose of Consensus Hemagglutinin-Based Virus-Like Particles Vaccine Protects Chickens against Divergent H5 Subtype Influenza Viruses

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Peipei Wu

2017-11-01

Full Text Available The H5 subtype highly pathogenic avian influenza (HPAI virus is one of the greatest threats to global poultry industry. To develop broadly protective H5 subunit vaccine, a recombinant consensus HA sequence (rHA was constructed and expressed in virus-like particles (rHA VLPs in the baculovirus-insect cell system. The efficacy of the rHA VLPs vaccine with or without immunopotentiator (CVCVA5 was assessed in chickens. Compared to the commercial Re6 or Re6-CVCVA5 vaccines, single dose immunization of chickens with rHA VLPs or rHA-CVCVA5 vaccines induced higher levels of serum hemagglutinin inhibition titers and neutralization titers, mucosal antibodies, IFN-γ and IL-4 cytokines in sera, and cytotoxic T lymphocyte responses. The rHA VLPs vaccine was superior to the commercial Re6 vaccine in conferring cross-protection against different clades of H5 subtype viruses. This study reports that H5 subtype consensus HA VLP single dose vaccination provides broad protection against HPAI virus in chickens.

The Gut Microbiota in Host Metabolism and Pathogen Challenges

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Holm, Jacob Bak

The human microbiota consists of a complex community of microbial cells that live on and inside each person in a close relationship with their host. The majority of the microbial cells are harboured by the gastro intestinal tract where 10-100 trillion bacteria reside. The microbiota is a dynamic...... community where both composition and function can be affected by changes in the local environment. With the microbiota containing ~150 times more genes than the human host, the microbiota provides a large modifiable “secondary genome” (metagenome). Within the last decade, changes in the gut microbiota...... composition has indeed been established as a factor contributing to the health of the host. Therefore, being able to understand, control and modify the gut microbiota is a promising way of improving health. The following thesis is based on four different projects investigating the murine gut microbiota...

C7L family of poxvirus host range genes inhibits antiviral activities induced by type I interferons and interferon regulatory factor 1.

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Meng, Xiangzhi; Schoggins, John; Rose, Lloyd; Cao, Jingxin; Ploss, Alexander; Rice, Charles M; Xiang, Yan

2012-04-01

Vaccinia virus (VACV) K1L and C7L function equivalently in many mammalian cells to support VACV replication and antagonize antiviral activities induced by type I interferons (IFNs). While K1L is limited to orthopoxviruses, genes that are homologous to C7L are found in diverse mammalian poxviruses. In this study, we showed that the C7L homologues from sheeppox virus and swinepox virus could rescue the replication defect of a VACV mutant deleted of both K1L and C7L (vK1L(-)C7L(-)). Interestingly, the sheeppox virus C7L homologue could rescue the replication of vK1L(-)C7L(-) in human HeLa cells but not in murine 3T3 and LA-4 cells, in contrast to all other C7L homologues. Replacing amino acids 134 and 135 of the sheeppox virus C7L homologue, however, made it functional in the two murine cell lines, suggesting that these two residues are critical for antagonizing a putative host restriction factor which has some subtle sequence variation in human and murine cells. Furthermore, the C7L family of host range genes from diverse mammalian poxviruses were all capable of antagonizing type I IFN-induced antiviral activities against VACV. Screening of a library of more than 350 IFN-stimulated genes (ISGs) identified interferon-regulated factor 1 (IRF1) as an inhibitor of vK1L(-)C7L(-) but not wild-type VACV. Expression of either K1L or C7L, however, rendered vK1L(-)C7L(-) resistant to IRF1-induced antiviral activities. Altogether, our data show that K1L and C7L antagonize IRF1-induced antiviral activities and that the host modulation function of C7L is evolutionally conserved in all poxviruses that can readily replicate in tissue-cultured mammalian cells.

The specificity of host-bat fly interaction networks across vegetation and seasonal variation.

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Zarazúa-Carbajal, Mariana; Saldaña-Vázquez, Romeo A; Sandoval-Ruiz, César A; Stoner, Kathryn E; Benitez-Malvido, Julieta

2016-10-01

Vegetation type and seasonality promote changes in the species composition and abundance of parasite hosts. However, it is poorly known how these variables affect host-parasite interaction networks. This information is important to understand the dynamics of parasite-host relationships according to biotic and abiotic changes. We compared the specialization of host-bat fly interaction networks, as well as bat fly and host species composition between upland dry forest and riparian forest and between dry and rainy seasons in a tropical dry forest in Jalisco, Mexico. Bat flies were surveyed by direct collection from bats. Our results showed that host-bat fly interaction networks were more specialized in upland dry forest compared to riparian forest. Bat fly species composition was different between the dry and rainy seasons, while host species composition was different between upland dry forest and riparian forest. The higher specialization in upland dry forest could be related to the differences in bat host species composition and their respective roosting habits. Variation in the composition of bat fly species between dry and rainy seasons coincides with the seasonal shifts in their species richness. Our study confirms the high specialization of host-bat fly interactions and shows the importance of biotic and abiotic factors to understand the dynamics of parasite-host interactions.

A randomized study of the prevention of acute graft-versus-host disease

International Nuclear Information System (INIS)

Ramsay, N.K.C.; Kersey, J.H.; Robison, L.L.; McGlave, P.B.; Woods, W.G.; Krivit, W.; Kim, T.H.; Goldman, A.I.; Nesbit, M.E. Jr.

1982-01-01

Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 percent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants

Multiple blood feeding and host-seeking behavior in Aedes aegypti and Aedes albopictus (Diptera: Culicidae).

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Farjana, Thahsin; Tuno, Nobuko

2013-07-01

The body size of mosquitoes can influence a number of bionomic factors, such as their blood-feeding ability, host attack rate, and fecundity. All of these traits are important determinants of their potential to transmit diseases. Among abiotic and biotic factors, high temperature and low nutrition in the developing stages of mosquitoes generally result in small adults. We studied the relationship between body size and multiple feeding in a gonotrophic cycle and some fecundity attributes by using three strains of two competent vector species, Aedes aegypti (L.) and Aedes albopictus (Skuse). We raised small and large mosquitoes under low and high food conditions in the laboratory to measure parameters of fecundity and blood-feeding behavior. Fecundity was positively correlated with body size in both species, whereas the number of bloodmeals, the frequency of host-seeking behavior, and egg retention were negatively correlated with body size in the Ae. albopictus Nagasaki strain. We found that multiple feeding and host-seeking behavior were negatively correlated with body size, i.e., small mosquitoes tended to have more contact with hosts. We found that two mechanisms that inhibit engorged mosquitoes from seeking out hosts, distension-induced and oocyte-induced inhibition, were not strong enough to limit host-seeking behavior, and multiple feeding increased fecundity. Size-dependent multiple feeding and host-seeking behavior affect contact frequency with hosts and should be considered when predicting how changes in mosquito body size affect disease transmission.

Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients.

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Sousa, Rita de; França, Ana; Dória Nòbrega, Sónia; Belo, Adelaide; Amaro, Mario; Abreu, Tiago; Poças, José; Proença, Paula; Vaz, José; Torgal, Jorge; Bacellar, Fátima; Ismail, Nahed; Walker, David H

2008-08-15

The pathophysiologic mechanisms that determine the severity of Mediterranean spotted fever (MSF) and the host-related and microbe-related risk factors for a fatal outcome are incompletely understood. This prospective study used univariate and multivariate analyses to determine the risk factors for a fatal outcome for 140 patients with Rickettsia conorii infection admitted to 13 Portuguese hospitals during 1994-2006 with documented identification of the rickettsial strain causing their infection. A total of 71 patients (51%) were infected with the Malish strain of Rickettsia conorii, and 69 (49%) were infected with the Israeli spotted fever (ISF) strain. Patients were admitted to the intensive care unit (40 [29%]), hospitalized as routine inpatients (95[67%]), or managed as outpatients (5[4%]). Death occurred in 29 adults (21%). A fatal outcome was significantly more likely for patients infected with the ISF strain, and alcoholism was a risk factor. The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, obtundation and/or confusion, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated levels of hepatic enzymes and creatine kinase. Some, but not all, of these findings were observed more often in ISF strain-infected patients. Although fatalities and similar clinical manifestations occurred among both groups of patients, the ISF strain was more virulent than the Malish strain. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strongly associated with a fatal outcome.

Host and geographic structure of endophytic and endolichenic fungi at a continental scale.

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U'Ren, Jana M; Lutzoni, François; Miadlikowska, Jolanta; Laetsch, Alexander D; Arnold, A Elizabeth

2012-05-01

Endophytic and endolichenic fungi occur in healthy tissues of plants and lichens, respectively, playing potentially important roles in the ecology and evolution of their hosts. However, previous sampling has not comprehensively evaluated the biotic, biogeographic, and abiotic factors that structure their communities. Using molecular data we examined the diversity, composition, and distributions of 4154 endophytic and endolichenic Ascomycota cultured from replicate surveys of ca. 20 plant and lichen species in each of five North American sites (Madrean coniferous forest, Arizona; montane semideciduous forest, North Carolina; scrub forest, Florida; Beringian tundra and forest, western Alaska; subalpine tundra, eastern central Alaska). Endolichenic fungi were more abundant and diverse per host species than endophytes, but communities of endophytes were more diverse overall, reflecting high diversity in mosses and lycophytes. Endophytes of vascular plants were largely distinct from fungal communities that inhabit mosses and lichens. Fungi from closely related hosts from different regions were similar in higher taxonomy, but differed at shallow taxonomic levels. These differences reflected climate factors more strongly than geographic distance alone. Our study provides a first evaluation of endophytic and endolichenic fungal associations with their hosts at a continental scale. Both plants and lichens harbor abundant and diverse fungal communities whose incidence, diversity, and composition reflect the interplay of climatic patterns, geographic separation, host type, and host lineage. Although culture-free methods will inform future work, our study sets the stage for empirical assessments of ecological specificity, metabolic capability, and comparative genomics.

Complex Virus-Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview.

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Li, Su; Wang, Jinghan; Yang, Qian; Naveed Anwar, Muhammad; Yu, Shaoxiong; Qiu, Hua-Ji

2017-07-05

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV-host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus-host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding.

Quantifying host potentials: indexing postharvest fresh fruits for spotted wing Drosophila, Drosophila suzukii.

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David E Bellamy

Full Text Available Novel methodology is presented for indexing the relative potential of hosts to function as resources. A Host Potential Index (HPI was developed as a practical framework to express relative host potential based on combining results from one or more independent studies, such as those examining host selection, utilization, and physiological development of the organism resourcing the host. Several aspects of the HPI are addressed including: 1 model derivation; 2 influence of experimental design on establishing host rankings for a study type (no choice, two-choice, and multiple-choice; and, 3 variable selection and weighting associated with combining multiple studies. To demonstrate application of the HPI, results from the interactions of spotted wing drosophila (SWD, Drosophila suzukii Matsumura (Diptera: Drosophilidae, with seven "reported" hosts (blackberries, blueberries, sweet cherries, table grapes, peaches, raspberries, and strawberries in a postharvest scenario were analyzed. Four aspects of SWD-host interaction were examined: attraction to host volatiles; population-level oviposition performance; individual-level oviposition performance; and key developmental factors. Application of HPI methodology indicated that raspberries ( (meanHPIvaried  = 301.9±8.39; rank 1 of 7 have the greatest potential to serve as a postharvest host for SWD relative to the other fruit hosts, with grapes ( (meanHPIvaried  = 232.4±3.21; rank 7 of 7 having the least potential.

Towards a better understanding of Lactobacillus rhamnosus GG - host interactions

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2014-01-01

Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotic strains. Various health effects are well documented including the prevention and treatment of gastro-intestinal infections and diarrhea, and stimulation of immune responses that promote vaccination or even prevent certain allergic symptoms. However, not all intervention studies could show a clinical benefit and even for the same conditions, the results are not univocal. Clearly, the host phenotype governed by age, genetics and environmental factors such as the endogenous microbiota, plays a role in whether individuals are responders or non-responders. However, we believe that a detailed knowledge of the bacterial physiology and the LGG molecules that play a key role in its host-interaction capacity is crucial for a better understanding of its potential health benefits. Molecules that were yet identified as important factors governing host interactions include its adhesive pili or fimbriae, its lipoteichoic acid molecules, its major secreted proteins and its galactose-rich exopolysaccharides, as well as specific DNA motifs. Nevertheless, future studies are needed to correlate specific health effects to these molecular effectors in LGG, and also in other probiotic strains. PMID:25186587

Host immunity, nutrition and coinfection alter longitudinal infection patterns of schistosomes in a free ranging African buffalo population.

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Brianna R Beechler

2017-12-01

Full Text Available Schistosomes are trematode parasites of global importance, causing infections in millions of people, livestock, and wildlife. Most studies on schistosomiasis, involve human subjects; as such, there is a paucity of longitudinal studies investigating parasite dynamics in the absence of intervention. As a consequence, despite decades of research on schistosomiasis, our understanding of its ecology in natural host populations is centered around how environmental exposure and acquired immunity influence acquisition of parasites, while very little is known about the influence of host physiology, coinfection and clearance in the absence of drug treatment. We used a 4-year study in free-ranging African buffalo to investigate natural schistosome dynamics. We asked (i what are the spatial and temporal patterns of schistosome infections; (ii how do parasite burdens vary over time within individual hosts; and (iii what host factors (immunological, physiological, co-infection and environmental factors (season, location explain patterns of schistosome acquisition and loss in buffalo? Schistosome infections were common among buffalo. Microgeographic structure explained some variation in parasite burdens among hosts, indicating transmission hotspots. Overall, parasite burdens ratcheted up over time; however, gains in schistosome abundance in the dry season were partially offset by losses in the wet season, with some hosts demonstrating complete clearance of infection. Variation among buffalo in schistosome loss was associated with immunologic and nutritional factors, as well as co-infection by the gastrointestinal helminth Cooperia fuelleborni. Our results demonstrate that schistosome infections are surprisingly dynamic in a free-living mammalian host population, and point to a role for host factors in driving variation in parasite clearance, but not parasite acquisition which is driven by seasonal changes and spatial habitat utilization. Our study illustrates

Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus.

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Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter; Jensen, Trine Hammer; Jensen, Tove Dannemann; Aasted, Bent; Blixenkrone-Møller, Merete

2009-07-30

The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper is still a problem worldwide. The broad host range of CDV creates a constant viral reservoir among wildlife animals. Our results demonstrated early humoral and cell-mediated immune responses (IFN-gamma) in DNA vaccinated mink compared to mock-vaccinated mink after challenge with a Danish wild-type CDV. The DNA vaccine-induced immunity protected the natural host against disease development.

The Trw type IV secretion system of Bartonella mediates host-specific adhesion to erythrocytes.

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Muriel Vayssier-Taussat

2010-06-01

Full Text Available Bacterial pathogens typically infect only a limited range of hosts; however, the genetic mechanisms governing host-specificity are poorly understood. The alpha-proteobacterial genus Bartonella comprises 21 species that cause host-specific intraerythrocytic bacteremia as hallmark of infection in their respective mammalian reservoirs, including the human-specific pathogens Bartonella quintana and Bartonella bacilliformis that cause trench fever and Oroya fever, respectively. Here, we have identified bacterial factors that mediate host-specific erythrocyte colonization in the mammalian reservoirs. Using mouse-specific Bartonella birtlesii, human-specific Bartonella quintana, cat-specific Bartonella henselae and rat-specific Bartonella tribocorum, we established in vitro adhesion and invasion assays with isolated erythrocytes that fully reproduce the host-specificity of erythrocyte infection as observed in vivo. By signature-tagged mutagenesis of B. birtlesii and mutant selection in a mouse infection model we identified mutants impaired in establishing intraerythrocytic bacteremia. Among 45 abacteremic mutants, five failed to adhere to and invade mouse erythrocytes in vitro. The corresponding genes encode components of the type IV secretion system (T4SS Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes. Strikingly, ectopic expression of Trw of rat-specific B. tribocorum in cat-specific B. henselae or human-specific B. quintana expanded their host range for erythrocyte infection to rat, demonstrating that Trw mediates host-specific erythrocyte infection. A molecular evolutionary analysis of the trw locus further indicated that the variable, surface-located TrwL and TrwJ might represent the T4SS components that determine host-specificity of erythrocyte parasitism. In conclusion, we show that the laterally acquired Trw T4SS diversified in the Bartonella lineage

Playing Hide and Seek: How Glycosylation of the Influenza Virus Hemagglutinin Can Modulate the Immune Response to Infection

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Michelle D. Tate

2014-03-01

Full Text Available Seasonal influenza A viruses (IAV originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the hemagglutinin (HA glycoprotein. The viral HA is the major target recognized by neutralizing antibodies and glycans have been proposed to shield antigenic sites on HA, thereby promoting virus survival in the face of widespread vaccination and/or infection. However, addition of glycans can also interfere with the receptor binding properties of HA and this must be compensated for by additional mutations, creating a fitness barrier to accumulation of glycosylation sites. In addition, glycans on HA are also recognized by phylogenetically ancient lectins of the innate immune system and the benefit provided by evasion of humoral immunity is balanced by attenuation of infection. Therefore, a fine balance must exist regarding the optimal pattern of HA glycosylation to offset competing pressures associated with recognition by innate defenses, evasion of humoral immunity and maintenance of virus fitness. In this review, we examine HA glycosylation patterns of IAV associated with pandemic and seasonal influenza and discuss recent advancements in our understanding of interactions between IAV glycans and components of innate and adaptive immunity.

Playing Hide and Seek: How Glycosylation of the Influenza Virus Hemagglutinin Can Modulate the Immune Response to Infection

Science.gov (United States)

Tate, Michelle D.; Job, Emma R.; Deng, Yi-Mo; Gunalan, Vithiagaran; Maurer-Stroh, Sebastian; Reading, Patrick C.

2014-01-01

Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the hemagglutinin (HA) glycoprotein. The viral HA is the major target recognized by neutralizing antibodies and glycans have been proposed to shield antigenic sites on HA, thereby promoting virus survival in the face of widespread vaccination and/or infection. However, addition of glycans can also interfere with the receptor binding properties of HA and this must be compensated for by additional mutations, creating a fitness barrier to accumulation of glycosylation sites. In addition, glycans on HA are also recognized by phylogenetically ancient lectins of the innate immune system and the benefit provided by evasion of humoral immunity is balanced by attenuation of infection. Therefore, a fine balance must exist regarding the optimal pattern of HA glycosylation to offset competing pressures associated with recognition by innate defenses, evasion of humoral immunity and maintenance of virus fitness. In this review, we examine HA glycosylation patterns of IAV associated with pandemic and seasonal influenza and discuss recent advancements in our understanding of interactions between IAV glycans and components of innate and adaptive immunity. PMID:24638204

Heartland virus NSs protein disrupts host defenses by blocking the TBK1 kinase-IRF3 transcription factor interaction and signaling required for interferon induction.

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Ning, Yun-Jia; Feng, Kuan; Min, Yuan-Qin; Deng, Fei; Hu, Zhihong; Wang, Hualin

2017-10-06

Heartland virus (HRTV) is a pathogenic phlebovirus related to the severe fever with thrombocytopenia syndrome virus (SFTSV), another phlebovirus causing life-threatening disease in humans. Previous findings have suggested that SFTSV can antagonize the host interferon (IFN) system via viral nonstructural protein (NSs)-mediated sequestration of antiviral signaling proteins into NSs-induced inclusion bodies. However, whether and how HRTV counteracts the host innate immunity is unknown. Here, we report that HRTV NSs (HNSs) also antagonizes IFN and cytokine induction and bolsters viral replication, although no noticeable inclusion body formation was observed in HNSs-expressing cells. Furthermore, HNSs inhibited the virus-triggered activation of IFN-β promoter by specifically targeting the IFN-stimulated response element but not the NF-κB response element. Consistently, HNSs blocked the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3, an IFN-stimulated response element-activating transcription factor). Reporter gene assays next showed that HNSs blockades the antiviral signaling mediated by RIG-I-like receptors likely at the level of TANK-binding kinase 1 (TBK1). Indeed, HNSs strongly interacts with TBK1 as indicated by confocal microscopy and pulldown analyses, and we also noted that the scaffold dimerization domain of TBK1 is required for the TBK1-HNSs interaction. Finally, pulldown assays demonstrated that HNSs expression dose-dependently diminishes a TBK1-IRF3 interaction, further explaining the mechanism for HNSs function. Collectively, these data suggest that HNSs, an antagonist of host innate immunity, interacts with TBK1 and thereby hinders the association of TBK1 with its substrate IRF3, thus blocking IRF3 activation and transcriptional induction of the cellular antiviral responses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Host transcription factor Speckled 110 kDa (Sp110), a nuclear body protein, is hijacked by hepatitis B virus protein X for viral persistence.

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Sengupta, Isha; Das, Dipanwita; Singh, Shivaram Prasad; Chakravarty, Runu; Das, Chandrima

2017-12-15

Promyelocytic leukemia nuclear bodies (PML-NB) are sub-nuclear organelles that are the hub of numerous proteins. DNA/RNA viruses often hijack the cellular factors resident in PML-NBs to promote their proliferation in host cells. Hepatitis B virus (HBV), belonging to Hepadnaviridae family, remains undetected in early infection as it does not induce the innate immune response and is known to be the cause of several hepatic diseases leading to cirrhosis and hepatocellular carcinoma. The association of PML-NB proteins and HBV is being addressed in a number of recent studies. Here, we report that the PML-NB protein Speckled 110 kDa (Sp110) is SUMO1-modified and undergoes a deSUMOylation-driven release from the PML-NB in the presence of HBV. Intriguingly, Sp110 knockdown significantly reduced viral DNA load in the culture supernatant by activation of the type I interferon-response pathway. Furthermore, we found that Sp110 differentially regulates several direct target genes of hepatitis B virus protein X (HBx), a viral co-factor. Subsequently, we identified Sp110 as a novel interactor of HBx and found this association to be essential for the exit of Sp110 from the PML-NB during HBV infection and HBx recruitment on the promoter of these genes. HBx, in turn, modulates the recruitment of its associated transcription cofactors p300/HDAC1 to these co-regulated genes, thereby altering the host gene expression program in favor of viral persistence. Thus, we report a mechanism by which HBV can evade host immune response by hijacking the PML-NB protein Sp110, and therefore, we propose it to be a novel target for antiviral therapy. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The role of host traits, season and group size on parasite burdens in a cooperative mammal.

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Hermien Viljoen

Full Text Available The distribution of parasites among hosts is often characterised by a high degree of heterogeneity with a small number of hosts harbouring the majority of parasites. Such patterns of aggregation have been linked to variation in host exposure and susceptibility as well as parasite traits and environmental factors. Host exposure and susceptibility may differ with sexes, reproductive effort and group size. Furthermore, environmental factors may affect both the host and parasite directly and contribute to temporal heterogeneities in parasite loads. We investigated the contributions of host and parasite traits as well as season on parasite loads in highveld mole-rats (Cryptomys hottentotus pretoriae. This cooperative breeder exhibits a reproductive division of labour and animals live in colonies of varying sizes that procreate seasonally. Mole-rats were parasitised by lice, mites, cestodes and nematodes with mites (Androlaelaps sp. and cestodes (Mathevotaenia sp. being the dominant ecto- and endoparasites, respectively. Sex and reproductive status contributed little to the observed parasite prevalence and abundances possibly as a result of the shared burrow system. Clear seasonal patterns of parasite prevalence and abundance emerged with peaks in summer for mites and in winter for cestodes. Group size correlated negatively with mite abundance while it had no effect on cestode burdens and group membership affected infestation with both parasites. We propose that the mode of transmission as well as social factors constrain parasite propagation generating parasite patterns deviating from those commonly predicted.

Determinants of glycan receptor specificity of H2N2 influenza A virus hemagglutinin.

Science.gov (United States)

Viswanathan, Karthik; Koh, Xiaoying; Chandrasekaran, Aarthi; Pappas, Claudia; Raman, Rahul; Srinivasan, Aravind; Shriver, Zachary; Tumpey, Terrence M; Sasisekharan, Ram

2010-10-29

The H2N2 subtype of influenza A virus was responsible for the Asian pandemic of 1957-58. However, unlike other subtypes that have caused pandemics such as H1N1 and H3N2, which continue to circulate among humans, H2N2 stopped circulating in the human population in 1968. Strains of H2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. Such an event is a potential global health concern because of the waning population immunity to H2 hemagglutinin (HA). The first step in such a cross-species transmission and human adaptation of influenza A virus is the ability for its surface glycoprotein HA to bind to glycan receptors expressed in the human upper respiratory epithelia. Recent structural and biochemical studies have focused on understanding the glycan receptor binding specificity of the 1957-58 pandemic H2N2 HA. However, there has been considerable HA sequence divergence in the recent avian-adapted H2 strains from the pandemic H2N2 strain. Using a combination of structural modeling, quantitative glycan binding and human respiratory tissue binding methods, we systematically identify mutations in the HA from a recent avian-adapted H2N2 strain (A/Chicken/PA/2004) that make its quantitative glycan receptor binding affinity (defined using an apparent binding constant) comparable to that of a prototypic pandemic H2N2 (A/Albany/6/58) HA.

Determinants of glycan receptor specificity of H2N2 influenza A virus hemagglutinin.

Directory of Open Access Journals (Sweden)

Karthik Viswanathan

Full Text Available The H2N2 subtype of influenza A virus was responsible for the Asian pandemic of 1957-58. However, unlike other subtypes that have caused pandemics such as H1N1 and H3N2, which continue to circulate among humans, H2N2 stopped circulating in the human population in 1968. Strains of H2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. Such an event is a potential global health concern because of the waning population immunity to H2 hemagglutinin (HA. The first step in such a cross-species transmission and human adaptation of influenza A virus is the ability for its surface glycoprotein HA to bind to glycan receptors expressed in the human upper respiratory epithelia. Recent structural and biochemical studies have focused on understanding the glycan receptor binding specificity of the 1957-58 pandemic H2N2 HA. However, there has been considerable HA sequence divergence in the recent avian-adapted H2 strains from the pandemic H2N2 strain. Using a combination of structural modeling, quantitative glycan binding and human respiratory tissue binding methods, we systematically identify mutations in the HA from a recent avian-adapted H2N2 strain (A/Chicken/PA/2004 that make its quantitative glycan receptor binding affinity (defined using an apparent binding constant comparable to that of a prototypic pandemic H2N2 (A/Albany/6/58 HA.

Establishing the relative importance of sympatric definitive hosts in the transmission of the sealworm, Pseudoterranova decipiens: a host-community approach

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F Javier Aznar

2001-11-01

Full Text Available The importance of a given host to a particular parasite can be determined according to three different criteria: host preference, host physiological suitability and host contribution to transmission. Most studies on the sealworm Pseudoterranova decipiens have focussed on the latter factor, but few attempts have been made to develop a quantitative transmission model evaluating the relative importance of each host. The purpose of this study was to propose a flow-chart model to study sealworm transmission within a seal community. The model was applied to hypothetical data of four seal species acting as definitive hosts of P. decipiens sensu stricto in eastern Canada: harp seal Phoca groenlandica, harbour seal P. vitulina, grey seal Halichoerus grypus and hooded seal Cystophora cristata. The dynamics of the model was studied using population estimates from 1990 to 1996. To illustrate the interrelationship of the seal populations in the flow dynamics, the model’s behaviour was explored by manipulation of the harp seal population size. The results showed that grey seals accounted by far for most transmission from and to the seals. The harbour seal population also sustained a biologically significant proportion of the flow, whereas the role of hooded and harp seals seemed negligible despite their large population sizes. The hypothetical removal of the harp seal population resulted in small increases in the relative flows to the other seals. These results conform to previous qualitative assessments on the relative importance of these seal species in sealworm transmission. The model provided some heuristic rules useful to understand transmission patterns. The data suggested that the harbour seal population should be about twice that of the grey seals to account for a larger share of transmission than grey seals. Although this is unlikely to occur at a large geographic scale, harbour seals outnumber grey seals in some areas and, therefore, the role of

Gnotobiotic mouse model's contribution to understanding host-pathogen interactions

Czech Academy of Sciences Publication Activity Database

Kubelková, K.; Benuchová, M.; Kozáková, Hana; Šinkora, Marek; Kročová, Z.; Pejchal, J.; Macela, A.

2016-01-01

Roč. 73, č. 20 (2016), s. 3961-3969 ISSN 1420-682X R&D Projects: GA ČR GA15-02274S Institutional support: RVO:61388971 Keywords : Germ- free model * Gnotobiology * Host-pathogen interaction Subject RIV: EC - Immunology Impact factor: 5.788, year: 2016

Survival and evolution of a large multidrug resistance plasmid in new clinical bacterial hosts

DEFF Research Database (Denmark)

Porse, Andreas; Schønning, Kristian; Munck, Christian

2016-01-01

sequencing to show that the long-term persistence and molecular integrity of the plasmid is highly influenced by multiple factors within a 25 kb plasmid region constituting a host-dependent burden. In the E. coli hosts investigated here, improved plasmid stability readily evolves via IS26 mediated deletions...... consistently followed by all evolved E. coli lineages exposes a trade-off between horizontal and vertical transmission that may ultimately limit the dissemination potential of clinical multidrug resistance plasmids in these hosts....

Host-microbiota interplay in mediating immune disorders.

Science.gov (United States)

Felix, Krysta M; Tahsin, Shekha; Wu, Hsin-Jung Joyce

2018-04-01

To maintain health, the immune system must maintain a delicate balance between eliminating invading pathogens and avoiding immune disorders such as autoimmunity and allergies. The gut microbiota provide essential health benefits to the host, particularly by regulating immune homeostasis. Dysbiosis, an alteration and imbalance of the gut microbiota, is associated with the development of several autoimmune diseases in both mice and humans. In this review, we discuss recent advances in understanding how certain factors, such as age and gender, affect the gut microbiota, which in turn can influence the development of autoimmune diseases. The age factor in microbiota-dependent immune disorders indicates a window of opportunity for future diagnostic and therapeutic approaches. We also discuss unique commensal bacteria with strong immunomodulatory activity. Finally, we provide an overview of the potential molecular mechanisms whereby gut microbiota induce autoimmunity, as well as the evidence that gut microbiota trigger extraintestinal diseases by inducing the migration of gut-derived immune cells. Elucidating the interaction of gut microbiota and the host immune system will help us understand the pathogenesis of immune disorders, and provide us with new foundations to develop novel immuno- or microbe-targeted therapies. © 2017 New York Academy of Sciences.

Limited by the host: Host age hampers establishment of holoparasite Cuscuta epithymum

Science.gov (United States)

Meulebrouck, Klaar; Verheyen, Kris; Brys, Rein; Hermy, Martin

2009-07-01

A good understanding of the relationship between plant establishment and the ecosystem of which they are part of is needed to conserve rare plant species. Introduction experiments offer a direct test of recruitment limitation, but generally only the seed germination and seedling phases are monitored. Thus the relative importance of different establishment stages in the process of recruitment is not considered. This is particularly true for parasitic plants where empirical data are generally missing. During two consecutive growing seasons we examined the effect of heathland management applications, degree of heathland succession (pioneer, building and mature phase) and seed-density on the recruitment and establishment of the endangered holoparasite Cuscuta epithymum. In general, recruitment after two growing seasons was low with 4.79% of the sown seeds that successfully emerged to the seedling stage and a final establishment of 89 flowering adults (i.e. <1.5% of the sown seeds). Although a higher seed-density resulted in a higher number of seedlings, seed-density did not significantly affected relative germination percentages. The management type and subsequent heath succession had no significant effect on seedling emergence; whereas, seedling attachment to the host, establishment and growth to full-grown size were hampered in older heath vegetation (i.e. high, dense, and mature canopy). Establishment was most successful in turf-cut pioneer heathland, characterised by a relatively open and low vegetation of young Calluna vulgaris. The age of C. vulgaris, C. epithymum's main host, proved to be the most limiting factor. These results emphasise the importance of site quality (i.e. successional phase of its host) on recruitment success of C. epithymum, which is directly affected by the management applied to the vegetation. Lack of any heathland management will thus seriously restrict establishment of the endangered parasite.

Host body size and the diversity of tick assemblages on Neotropical vertebrates

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Helen J. Esser

2016-12-01

Full Text Available Identifying the factors that influence the species diversity and distribution of ticks (Acari: Ixodida across vertebrate host taxa is of fundamental ecological and medical importance. Host body size is considered one of the most important determinants of tick abundance, with larger hosts having higher tick burdens. The species diversity of tick assemblages should also be greater on larger-bodied host species, but empirical studies testing this hypothesis are lacking. Here, we evaluate this relationship using a comparative dataset of feeding associations from Panama between 45 tick species and 171 host species that range in body size by three orders of magnitude. We found that tick species diversity increased with host body size for adult ticks but not for immature ticks. We also found that closely related host species tended to have similar tick species diversity, but correcting for host phylogeny did not alter the relationships between host body size and tick species diversity. The distribution of tick species was highly aggregated, with approximately 20% of the host species harboring 80% of all tick species, following the Pareto principle or 20/80 Rule. Thus, the aggregated pattern commonly observed for tick burdens and disease transmission also holds for patterns of tick species richness. Our finding that the adult ticks in this system preferentially parasitize large-bodied host species suggests that the ongoing anthropogenic loss of large-bodied vertebrates is likely to result in host-tick coextinction events, even when immature stages feed opportunistically. As parasites play critical roles in ecological and evolutionary processes, such losses may profoundly affect ecosystem functioning and services.

Adaptation to the Host Environment by Plant-Pathogenic Fungi.

Science.gov (United States)

van der Does, H Charlotte; Rep, Martijn

2017-08-04

Many fungi can live both saprophytically and as endophyte or pathogen inside a living plant. In both environments, complex organic polymers are used as sources of nutrients. Propagation inside a living host also requires the ability to respond to immune responses of the host. We review current knowledge of how plant-pathogenic fungi do this. First, we look at how fungi change their global gene expression upon recognition of the host environment, leading to secretion of effectors, enzymes, and secondary metabolites; changes in metabolism; and defense against toxic compounds. Second, we look at what is known about the various cues that enable fungi to sense the presence of living plant cells. Finally, we review literature on transcription factors that participate in gene expression in planta or are suspected to be involved in that process because they are required for the ability to cause disease.

Virus-host interaction in feline immunodeficiency virus (FIV) infection.

Science.gov (United States)

Taniwaki, Sueli Akemi; Figueiredo, Andreza Soriano; Araujo, João Pessoa

2013-12-01

Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus-host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

The role of beetle and host volatiles in host colonization in the European oak bark beetle, Scolytus intricatus (Ratzeburg) (Col., Scolytidae)

Czech Academy of Sciences Publication Activity Database

Hovorka, Oldřich; Kindl, Jiří; Kalinová, Blanka; Knížek, M.; Vrkočová, Pavlína; Koutek, Bohumír

2005-01-01

Roč. 129, č. 4 (2005), 221-226 ISSN 0931-2048 R&D Projects: GA ČR(CZ) GA203/97/0037; GA MZe(CZ) QD0332 Institutional research plan: CEZ:AV0Z4055905 Keywords : bark beetles * host colonization * pheromones Subject RIV: CC - Organic Chemistry Impact factor: 0.703, year: 2005

The Porphyromonas gingivalis hemagglutinins HagB and HagC are major mediators of adhesion and biofilm formation.

Science.gov (United States)

Connolly, E; Millhouse, E; Doyle, R; Culshaw, S; Ramage, G; Moran, G P

2017-02-01

Porphyromonas gingivalis is a bacterium associated with chronic periodontitis that possesses a family of genes encoding hemagglutinins required for heme acquisition. In this study we generated ΔhagB and ΔhagC mutants in strain W83 and demonstrate that both hagB and hagC are required for adherence to oral epithelial cells. Unexpectedly, a double ΔhagB/ΔhagC mutant had less severe adherence defects than either of the single mutants, but was found to exhibit increased expression of the gingipain-encoding genes rgpA and kgp, suggesting that a ΔhagB/ΔhagC mutant is only viable in populations of cells that exhibit increased expression of genes involved in heme acquisition. Disruption of hagB in the fimbriated strain ATCC33277 demonstrated that HagB is also required for stable attachment of fimbriated bacteria to oral epithelial cells. Mutants of hagC were also found to form defective single and multi-species biofilms that had reduced biomass relative to biofilms formed by the wild-type strain. This study highlights the hitherto unappreciated importance of these genes in oral colonization and biofilm formation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Structure, Receptor Binding, and Antigenicity of Influenza Virus Hemagglutinins from the 1957 H2N2 Pandemic

Energy Technology Data Exchange (ETDEWEB)

Xu, Rui; McBride, Ryan; Paulson, James C.; Basler, Christopher F.; Wilson, Ian A. (Sinai); (Scripps)

2010-03-04

The hemagglutinin (HA) envelope protein of influenza viruses mediates essential viral functions, including receptor binding and membrane fusion, and is the major viral antigen for antibody neutralization. The 1957 H2N2 subtype (Asian flu) was one of the three great influenza pandemics of the last century and caused 1 million deaths globally from 1957 to 1968. Three crystal structures of 1957 H2 HAs have been determined at 1.60 to 1.75 {angstrom} resolutions to investigate the structural basis for their antigenicity and evolution from avian to human binding specificity that contributed to its introduction into the human population. These structures, which represent the highest resolutions yet recorded for a complete ectodomain of a glycosylated viral surface antigen, along with the results of glycan microarray binding analysis, suggest that a hydrophobicity switch at residue 226 and elongation of receptor-binding sites were both critical for avian H2 HA to acquire human receptor specificity. H2 influenza viruses continue to circulate in birds and pigs and, therefore, remain a substantial threat for transmission to humans. The H2 HA structure also reveals a highly conserved epitope that could be harnessed in the design of a broader and more universal influenza A virus vaccine.

The host immunological response to cancer therapy: An emerging concept in tumor biology

International Nuclear Information System (INIS)

Voloshin, Tali; Voest, Emile E.; Shaked, Yuval

2013-01-01

Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction—both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. -- Highlights: • Cancer therapy induces host molecular and cellular pro-tumorigenic effects. • Host effects in response to therapy may promote tumor relapse and metastasis. • The reactive host consists of immunological mediators promoting tumor re-growth. • Blocking therapy-induced host mediators may improve outcome

The host immunological response to cancer therapy: An emerging concept in tumor biology

Energy Technology Data Exchange (ETDEWEB)

Voloshin, Tali [Department of Molecular Pharmacology, Rappaport Faculty of Medicine and the Rappaport Institute, Technion—Israel Institute of Technology, 1 Efron Street, Bat Galim, Haifa 31096 (Israel); Voest, Emile E. [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Shaked, Yuval, E-mail: yshaked@tx.technion.ac.il [Department of Molecular Pharmacology, Rappaport Faculty of Medicine and the Rappaport Institute, Technion—Israel Institute of Technology, 1 Efron Street, Bat Galim, Haifa 31096 (Israel)

2013-07-01

Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction—both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. -- Highlights: • Cancer therapy induces host molecular and cellular pro-tumorigenic effects. • Host effects in response to therapy may promote tumor relapse and metastasis. • The reactive host consists of immunological mediators promoting tumor re-growth. • Blocking therapy-induced host mediators may improve outcome.

Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in Reservoir-Host Populations.

Directory of Open Access Journals (Sweden)

Raina K Plowright

2016-08-01

Full Text Available Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host-pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife.

Protective immunity provided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus

International Nuclear Information System (INIS)

Oh, Sang Kon; Stegman, Brian; Pendleton, C. David; Ota, Martin O.; Pan, C.-H.; Griffin, Diane E.; Burke, Donald S.; Berzofsky, Jay A.

2006-01-01

Natural infection and vaccination with a live-attenuated measles virus (MV) induce CD8 + T-cell-mediated immune responses that may play a central role in controlling MV infection. In this study, we show that newly identified human HLA-A2 epitopes from MV hemagglutinin (H) and fusion (F) proteins induced protective immunity in HLA-A2 transgenic mice challenged with recombinant vaccinia viruses expressing F or H protein. HLA-A2 epitopes were predicted and synthesized. Five and four peptides from H and F, respectively, bound to HLA-A2 molecules in a T2-binding assay, and four from H and two from F could induce peptide-specific CD8 + T cell responses in HLA-A2 transgenic mice. Further experiments proved that three peptides from H (H9-567, H10-250, and H10-516) and one from F protein (F9-57) were endogenously processed and presented on HLA-A2 molecules. All peptides tested in this study are common to 5 different strains of MV including Edmonston. In both A2K b and HHD-2 mice, the identified peptide epitopes induced protective immunity against recombinant vaccinia viruses expressing H or F. Because F and H proteins induce neutralizing antibodies, they are major components of new vaccine strategies, and therefore data from this study will contribute to the development of new vaccines against MV infection

Data from: Two different strategies of host manipulation allow parasites to persist in intermediate-definitive host systems

NARCIS (Netherlands)

Vries, de Lana; Langevelde, van F.

2017-01-01

Trophically-transmitted parasites start their development in an intermediate host, before they finish the development in their definitive host when the definitive host preys on the intermediate host. In intermediate-definitive host systems, two strategies of host manipulation have been evolved:

Herpesvirus papio 2 encodes a virion host shutoff function.

Science.gov (United States)

Bigger, John E; Martin, David W

2002-12-05

Infection of baboons with herpesvirus papio 2 (HVP-2) produces a disease that is similar to human infection with herpes simplex viruses (HSV). Molecular characterization of HVP-2 has demonstrated that the virion contains a factor which rapidly shuts off host cell protein synthesis after infection. Reduction of host cell protein synthesis occurs in parallel with the degradation of mRNA species. A homolog of the HSV virion host shutoff (vhs) gene was identified by Southern and DNA sequence analysis. The sequence of the HVP-2 vhs gene homolog had greater than 70% identity with the vhs genes of HSV 1 and 2. Disruption of the HVP-2 vhs open reading frame diminished the ability of the virus to shut off protein synthesis and degrade cellular mRNA, indicating that this gene was responsible for the vhs activity. The HVP-2 model system provides the opportunity to study the biological role of vhs in the context of a natural primate host. Further development of this system will provide a platform for proof-of-concept studies that will test the efficacy of vaccines that utilize vhs-deficient viruses.

Long-distance delivery of bacterial virulence factors by Pseudomonas aeruginosa outer membrane vesicles.

Directory of Open Access Journals (Sweden)

Jennifer M Bomberger

2009-04-01

Full Text Available Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane-derived vesicles (OMV secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including beta-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma membrane. These virulence factors enter the cytoplasm of the host cell via N-WASP-mediated actin trafficking, where they rapidly distribute to specific subcellular locations to affect host cell biology. We propose that secreted virulence factors are not released individually as naked proteins into the surrounding milieu where they may randomly contact the surface of the host cell, but instead bacterial derived OMV deliver multiple virulence factors simultaneously and directly into the host cell cytoplasm in a coordinated manner.

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

Diversity, distribution and host-species associations of epiphytic orchids in Nepal

Czech Academy of Sciences Publication Activity Database

Timsina, B.; Rokaya, Maan Bahadur; Münzbergová, Zuzana; Kindlmann, P.; Shrestha, B.; Bhattarai, B.; Raskoti, B. B.

2016-01-01

Roč. 25, č. 13 (2016), s. 2803-2819 ISSN 0960-3115 Institutional support: RVO:67985939 Keywords : species richness * host * Nepal Himalaya Subject RIV: EF - Botanics Impact factor: 2.265, year: 2016

Host-derived viral transporter protein for nitrogen uptake in infected marine phytoplankton

Science.gov (United States)

Chambouvet, Aurélie; Milner, David S.; Attah, Victoria; Terrado, Ramón; Lovejoy, Connie; Moreau, Hervé; Derelle, Évelyne; Richards, Thomas A.

2017-01-01

Phytoplankton community structure is shaped by both bottom–up factors, such as nutrient availability, and top–down processes, such as predation. Here we show that marine viruses can blur these distinctions, being able to amend how host cells acquire nutrients from their environment while also predating and lysing their algal hosts. Viral genomes often encode genes derived from their host. These genes may allow the virus to manipulate host metabolism to improve viral fitness. We identify in the genome of a phytoplankton virus, which infects the small green alga Ostreococcus tauri, a host-derived ammonium transporter. This gene is transcribed during infection and when expressed in yeast mutants the viral protein is located to the plasma membrane and rescues growth when cultured with ammonium as the sole nitrogen source. We also show that viral infection alters the nature of nitrogen compound uptake of host cells, by both increasing substrate affinity and allowing the host to access diverse nitrogen sources. This is important because the availability of nitrogen often limits phytoplankton growth. Collectively, these data show that a virus can acquire genes encoding nutrient transporters from a host genome and that expression of the viral gene can alter the nutrient uptake behavior of host cells. These results have implications for understanding how viruses manipulate the physiology and ecology of phytoplankton, influence marine nutrient cycles, and act as vectors for horizontal gene transfer. PMID:28827361

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.

Genomic diversification of enterococci in hosts: the role of the mobilome.

Science.gov (United States)

Santagati, Maria; Campanile, Floriana; Stefani, Stefania

2012-01-01

Enterococci are ubiquitous lactic acid bacteria, possessing a flexible nature that allows them to colonize various environments and hosts but also to be opportunistic pathogens. Many papers have contributed to a better understanding of: (i) the taxonomy of this complex group of microorganisms; (ii) intra-species variability; (iii) the role of different pathogenicity traits; and (iv) some markers related to the character of host-specificity, but the reasons of such incredible success of adaptability is still far from being fully explained. Recently, genomic-based studies have improved our understanding of the genome diversity of the most studied species, i.e., E. faecalis and E. faecium. From these studies, what is becoming evident is the role of the mobilome in adding new abilities to colonize new hosts and environments, and eventually in driving their evolution: specific clones associated with human infections or specific hosts can exist, but probably the consideration of these populations as strictly clonal groups is only partially correct. The variable presence of mobile genetic elements may, indeed, be one of the factors involved in the evolution of one specific group in a specific host and/or environment. Certainly more extensive studies using new high throughput technologies are mandatory to fully understand the evolution of predominant clones and species in different hosts and environments.

Staphylococcus aureus produces membrane-derived vesicles that induce host cell death.

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Mamata Gurung

Full Text Available Gram-negative bacteria produce outer membrane vesicles that play a role in the delivery of virulence factors to host cells. However, little is known about the membrane-derived vesicles (MVs produced by gram-positive bacteria. The present study examined the production of MVs from Staphylococcus aureus and investigated the delivery of MVs to host cells and subsequent cytotoxicity. Four S. aureus strains tested, two type strains and two clinical isolates, produced spherical nanovesicles during in vitro culture. MVs were also produced during in vivo infection of a clinical S. aureus isolate in a mouse pneumonia model. Proteomic analysis showed that 143 different proteins were identified in the S. aureus-derived MVs. S. aureus MVs were interacted with the plasma membrane of host cells via a cholesterol-rich membrane microdomain and then delivered their component protein A to host cells within 30 min. Intact S. aureus MVs induced apoptosis of HEp-2 cells in a dose-dependent manner, whereas lysed MVs neither delivered their component into the cytosol of host cells nor induced cytotoxicity. In conclusion, this study is the first report that S. aureus MVs are an important vehicle for delivery of bacterial effector molecules to host cells.

HIV protein sequence hotspots for crosstalk with host hub proteins.

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Mahdi Sarmady

Full Text Available HIV proteins target host hub proteins for transient binding interactions. The presence of viral proteins in the infected cell results in out-competition of host proteins in their interaction with hub proteins, drastically affecting cell physiology. Functional genomics and interactome datasets can be used to quantify the sequence hotspots on the HIV proteome mediating interactions with host hub proteins. In this study, we used the HIV and human interactome databases to identify HIV targeted host hub proteins and their host binding partners (H2. We developed a high throughput computational procedure utilizing motif discovery algorithms on sets of protein sequences, including sequences of HIV and H2 proteins. We identified as HIV sequence hotspots those linear motifs that are highly conserved on HIV sequences and at the same time have a statistically enriched presence on the sequences of H2 proteins. The HIV protein motifs discovered in this study are expressed by subsets of H2 host proteins potentially outcompeted by HIV proteins. A large subset of these motifs is involved in cleavage, nuclear localization, phosphorylation, and transcription factor binding events. Many such motifs are clustered on an HIV sequence in the form of hotspots. The sequential positions of these hotspots are consistent with the curated literature on phenotype altering residue mutations, as well as with existing binding site data. The hotspot map produced in this study is the first global portrayal of HIV motifs involved in altering the host protein network at highly connected hub nodes.

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

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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.

The potential for host switching via ecological fitting in the emerald ash borer-host plant system.

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Cipollini, Don; Peterson, Donnie L

2018-02-27

The traits used by phytophagous insects to find and utilize their ancestral hosts can lead to host range expansions, generally to closely related hosts that share visual and chemical features with ancestral hosts. Host range expansions often result from ecological fitting, which is the process whereby organisms colonize and persist in novel environments, use novel resources, or form novel associations with other species because of the suites of traits that they carry at the time they encounter the novel environment. Our objective in this review is to discuss the potential and constraints on host switching via ecological fitting in emerald ash borer, Agrilus planipennis, an ecologically and economically important invasive wood boring beetle. Once thought of as an ash (Fraxinus spp.) tree specialist, recent studies have revealed a broader potential host range than was expected for this insect. We discuss the demonstrated host-use capabilities of this beetle, as well as the potential for and barriers to the adoption of additional hosts by this beetle. We place our observations in the context of biochemical mechanisms that mediate the interaction of these beetles with their host plants and discuss whether evolutionary host shifts are a possible outcome of the interaction of this insect with novel hosts.

Diet dominates host genotype in shaping the murine gut microbiota

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Carmody, Rachel N.; Gerber, Georg K.; Luevano, Jesus M.; Gatti, Daniel M.; Somes, Lisa; Svenson, Karen L.; Turnbaugh, Peter J.

2014-01-01

SUMMARY Mammals exhibit marked inter-individual variations in their gut microbiota, but it remains unclear if this is primarily driven by host genetics or by extrinsic factors like dietary intake. To address this, we examined the effect of dietary perturbations on the gut microbiota of five inbred mouse strains, mice deficient for genes relevant to host-microbial interactions (MyD88−/−, NOD2−/−, ob/ob, and Rag1−/−), and >200 outbred mice. In each experiment, consumption of a high-fat, high-sugar diet reproducibly altered the gut microbiota despite differences in host genotype. The gut microbiota exhibited a linear dose response to dietary perturbations, taking an average of 3.5 days for each diet-responsive bacterial groups to reach a new steady state. Repeated dietary shifts demonstrated that most changes to the gut microbiota are reversible, while also uncovering bacteria whose abundance depends on prior consumption. These results emphasize the dominant role that diet plays in shaping inter-individual variations in host-associated microbial communities. PMID:25532804

Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

OpenAIRE

Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

1997-01-01

Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice ...

Fatty Acid Composition of Novel Host Jack Pine Do Not Prevent Host Acceptance and Colonization by the Invasive Mountain Pine Beetle and Its Symbiotic Fungus

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Ishangulyyeva, Guncha; Najar, Ahmed; Curtis, Jonathan M.

2016-01-01

Fatty acids are major components of plant lipids and can affect growth and development of insect herbivores. Despite a large literature examining the roles of fatty acids in conifers, relatively few studies have tested the effects of fatty acids on insect herbivores and their microbial symbionts. Particularly, whether fatty acids can affect the suitability of conifers for insect herbivores has never been studied before. Thus, we evaluated if composition of fatty acids impede or facilitate colonization of jack pine (Pinus banksiana) by the invasive mountain pine beetle (Dendroctonus ponderosae) and its symbiotic fungus (Grosmannia clavigera). This is the first study to examine the effects of tree fatty acids on any bark beetle species and its symbiotic fungus. In a novel bioassay, we found that plant tissues (hosts and non-host) amended with synthetic fatty acids at concentrations representative of jack pine were compatible with beetle larvae. Likewise, G. clavigera grew in media amended with lipid fractions or synthetic fatty acids at concentrations present in jack pine. In contrast, fatty acids and lipid composition of a non-host were not suitable for the beetle larvae or the fungus. Apparently, concentrations of individual, rather than total, fatty acids determined the suitability of jack pine. Furthermore, sampling of host and non-host tree species across Canada demonstrated that the composition of jack pine fatty acids was similar to the different populations of beetle’s historical hosts. These results demonstrate that fatty acids composition compatible with insect herbivores and their microbial symbionts can be important factor defining host suitability to invasive insects. PMID:27583820

Inhibiting host-pathogen interactions using membrane-based nanostructures.

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Bricarello, Daniel A; Patel, Mira A; Parikh, Atul N

2012-06-01

Virulent strains of bacteria and viruses recognize host cells by their plasma membrane receptors and often exploit the native translocation machinery to invade the cell. A promising therapeutic concept for early interruption of pathogen infection is to subvert this pathogenic trickery using exogenously introduced decoys that present high-affinity mimics of cellular receptors. This review highlights emerging applications of molecularly engineered lipid-bilayer-based nanostructures, namely (i) functionalized liposomes, (ii) supported colloidal bilayers or protocells and (iii) reconstituted lipoproteins, which display functional cellular receptors in optimized conformational and aggregative states. These decoys outcompete host cell receptors by preferentially binding to and neutralizing virulence factors of both bacteria and viruses, thereby promising a new approach to antipathogenic therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Consequences of symbiont co-infections for insect host phenyotypes

Czech Academy of Sciences Publication Activity Database

McLean, A. H. C.; Parker, B. J.; Hrček, Jan; Kavanagh, J. C.; Wellham, P. A. D.; Godfray, H. C. J.

2018-01-01

Roč. 87, č. 2 (2018), s. 478-488 ISSN 0021-8790 Institutional support: RVO:60077344 Keywords : aphids * co-infection * host-parasite interactions Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology Impact factor: 4.474, year: 2016 http://onlinelibrary.wiley.com/doi/10.1111/1365-2656.12705/epdf

Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge

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Li, Zhuo; Mooney, Alaina J.; Gabbard, Jon D.; Gao, Xiudan; Xu, Pei; Place, Ryan J.; Hogan, Robert J.; Tompkins, S. Mark

2013-01-01

A safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (HPAI) H5N1 outbreaks in the human population. The current FDA-approved H5N1 vaccine has serious limitations. A more efficacious H5N1 vaccine is urgently needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, is not known to cause any illness in humans. PIV5 is an attractive vaccine vector. In our studies, a single dose of a live recombinant PIV5 expressing a hemagglutinin (HA) gene of H5N1 (rPIV5-H5) from the H5N1 subtype provided sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. Furthermore, we have examined the effect of insertion of H5N1 HA at different locations within the PIV5 genome on the efficacy of a PIV5-based vaccine. Interestingly, insertion of H5N1 HA between the leader sequence, the de facto promoter of PIV5, and the first viral gene, nucleoprotein (NP), did not lead to a viable virus. Insertion of H5N1 HA between NP and the next gene, V/phosphorprotein (V/P), led to a virus that was defective in growth. We have found that insertion of H5N1 HA at the junction between the small hydrophobic (SH) gene and the hemagglutinin-neuraminidase (HN) gene gave the best immunity against HPAI H5N1 challenge: a dose as low as 1,000 PFU was sufficient to protect against lethal HPAI H5N1 challenge in mice. The work suggests that recombinant PIV5 expressing H5N1 HA has great potential as an HPAI H5N1 vaccine. PMID:23077314

Responses of wild small mammals to a pollution gradient: Host factors influence metal and metallothionein levels

International Nuclear Information System (INIS)

Fritsch, Clementine; Cosson, Richard P.; Coeurdassier, Michael; Raoul, Francis; Giraudoux, Patrick; Crini, Nadia; Vaufleury, Annette de; Scheifler, Renaud

2010-01-01

We investigated how host factors (species, age, gender) modulated Cd, Pb, Zn, and Cu concentrations, metallothionein levels (MTs) and their relationships in 7 sympatric small mammal species along a pollution gradient. Cd concentrations in liver and kidneys increased with age in all species. Age effect on other metals and MTs differs among species. Gender did not influence metal and MT levels except in the bank vole. Three patterns linking internal metal concentrations and MTs were observed along the gradient: a low metal accumulation with a (i) high (wood mouse) or (ii) low (bank vole) level of MTs accompanied by a slight or no increase of MTs with Cd accumulation; (iii) an elevated metal accumulation with a sharp increase of MTs (common and pygmy shrews). In risk assessment and biomonitoring perspectives, we conclude that measurements of MTs and metals might be associated because they cannot be interpreted properly when considered separately. - Age more than gender and species more than trophic group influence metallic trace element and metallothionein levels and their relationships in wild small mammals exposed to metals.

Structure homology and interaction redundancy for discovering virus–host protein interactions

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de Chassey, Benoît; Meyniel-Schicklin, Laurène; Aublin-Gex, Anne; Navratil, Vincent; Chantier, Thibaut; André, Patrice; Lotteau, Vincent

2013-01-01

Virus–host interactomes are instrumental to understand global perturbations of cellular functions induced by infection and discover new therapies. The construction of such interactomes is, however, technically challenging and time consuming. Here we describe an original method for the prediction of high-confidence interactions between viral and human proteins through a combination of structure and high-quality interactome data. Validation was performed for the NS1 protein of the influenza virus, which led to the identification of new host factors that control viral replication. PMID:24008843

Structure homology and interaction redundancy for discovering virus-host protein interactions.

Science.gov (United States)

de Chassey, Benoît; Meyniel-Schicklin, Laurène; Aublin-Gex, Anne; Navratil, Vincent; Chantier, Thibaut; André, Patrice; Lotteau, Vincent

2013-10-01

Virus-host interactomes are instrumental to understand global perturbations of cellular functions induced by infection and discover new therapies. The construction of such interactomes is, however, technically challenging and time consuming. Here we describe an original method for the prediction of high-confidence interactions between viral and human proteins through a combination of structure and high-quality interactome data. Validation was performed for the NS1 protein of the influenza virus, which led to the identification of new host factors that control viral replication.

Interaction of MYC with host cell factor-1 is mediated by the evolutionarily conserved Myc box IV motif.

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Thomas, L R; Foshage, A M; Weissmiller, A M; Popay, T M; Grieb, B C; Qualls, S J; Ng, V; Carboneau, B; Lorey, S; Eischen, C M; Tansey, W P

2016-07-07

The MYC family of oncogenes encodes a set of three related transcription factors that are overexpressed in many human tumors and contribute to the cancer-related deaths of more than 70,000 Americans every year. MYC proteins drive tumorigenesis by interacting with co-factors that enable them to regulate the expression of thousands of genes linked to cell growth, proliferation, metabolism and genome stability. One effective way to identify critical co-factors required for MYC function has been to focus on sequence motifs within MYC that are conserved throughout evolution, on the assumption that their conservation is driven by protein-protein interactions that are vital for MYC activity. In addition to their DNA-binding domains, MYC proteins carry five regions of high sequence conservation known as Myc boxes (Mb). To date, four of the Mb motifs (MbI, MbII, MbIIIa and MbIIIb) have had a molecular function assigned to them, but the precise role of the remaining Mb, MbIV, and the reason for its preservation in vertebrate Myc proteins, is unknown. Here, we show that MbIV is required for the association of MYC with the abundant transcriptional coregulator host cell factor-1 (HCF-1). We show that the invariant core of MbIV resembles the tetrapeptide HCF-binding motif (HBM) found in many HCF-interaction partners, and demonstrate that MYC interacts with HCF-1 in a manner indistinguishable from the prototypical HBM-containing protein VP16. Finally, we show that rationalized point mutations in MYC that disrupt interaction with HCF-1 attenuate the ability of MYC to drive tumorigenesis in mice. Together, these data expose a molecular function for MbIV and indicate that HCF-1 is an important co-factor for MYC.

A New Strategy to Reduce Influenza Escape: Detecting Therapeutic Targets Constituted of Invariance Groups

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Julie Lao

2017-03-01

Full Text Available The pathogenicity of the different flu species is a real public health problem worldwide. To combat this scourge, we established a method to detect drug targets, reducing the possibility of escape. Besides being able to attach a drug candidate, these targets should have the main characteristic of being part of an essential viral function. The invariance groups that are sets of residues bearing an essential function can be detected genetically. They consist of invariant and synthetic lethal residues (interdependent residues not varying or slightly varying when together. We analyzed an alignment of more than 10,000 hemagglutinin sequences of influenza to detect six invariance groups, close in space, and on the protein surface. In parallel we identified five potential pockets on the surface of hemagglutinin. By combining these results, three potential binding sites were determined that are composed of invariance groups located respectively in the vestigial esterase domain, in the bottom of the stem and in the fusion area. The latter target is constituted of residues involved in the spring-loaded mechanism, an essential step in the fusion process. We propose a model describing how this potential target could block the reorganization of the hemagglutinin HA2 secondary structure and prevent viral entry into the host cell.

Probing Molecular Insights into Zika Virus–Host Interactions

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Ina Lee

2018-05-01

Full Text Available The recent Zika virus (ZIKV outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies, and Guillain–Barré syndrome. In response to this global health crisis, unprecedented and world-wide efforts are taking place to study the ZIKV-related human diseases. Much has been learned about this virus in the areas of epidemiology, genetic diversity, protein structures, and clinical manifestations, such as consequences of ZIKV infection on fetal brain development. However, progress on understanding the molecular mechanism underlying ZIKV-associated neurologic disorders remains elusive. To date, we still lack a good understanding of; (1 what virologic factors are involved in the ZIKV-associated human diseases; (2 which ZIKV protein(s contributes to the enhanced viral pathogenicity; and (3 how do the newly adapted and pandemic ZIKV strains alter their interactions with the host cells leading to neurologic defects? The goal of this review is to explore the molecular insights into the ZIKV–host interactions with an emphasis on host cell receptor usage for viral entry, cell innate immunity to ZIKV, and the ability of ZIKV to subvert antiviral responses and to cause cytopathic effects. We hope this literature review will inspire additional molecular studies focusing on ZIKV–host Interactions.

Probing Molecular Insights into Zika Virus–Host Interactions

Science.gov (United States)

Lee, Ina; Li, Ge; Wang, Shusheng; Desprès, Philippe; Zhao, Richard Y.

2018-01-01

The recent Zika virus (ZIKV) outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies, and Guillain–Barré syndrome. In response to this global health crisis, unprecedented and world-wide efforts are taking place to study the ZIKV-related human diseases. Much has been learned about this virus in the areas of epidemiology, genetic diversity, protein structures, and clinical manifestations, such as consequences of ZIKV infection on fetal brain development. However, progress on understanding the molecular mechanism underlying ZIKV-associated neurologic disorders remains elusive. To date, we still lack a good understanding of; (1) what virologic factors are involved in the ZIKV-associated human diseases; (2) which ZIKV protein(s) contributes to the enhanced viral pathogenicity; and (3) how do the newly adapted and pandemic ZIKV strains alter their interactions with the host cells leading to neurologic defects? The goal of this review is to explore the molecular insights into the ZIKV–host interactions with an emphasis on host cell receptor usage for viral entry, cell innate immunity to ZIKV, and the ability of ZIKV to subvert antiviral responses and to cause cytopathic effects. We hope this literature review will inspire additional molecular studies focusing on ZIKV–host Interactions. PMID:29724036

The Drosophila melanogaster host model

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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