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Sample records for sars viruses identified

  1. Identifying SARS-CoV membrane protein amino acid residues linked to virus-like particle assembly.

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    Ying-Tzu Tseng

    Full Text Available Severe acute respiratory syndrome coronavirus (SARS-CoV membrane (M proteins are capable of self-assembly and release in the form of membrane-enveloped vesicles, and of forming virus-like particles (VLPs when coexpressed with SARS-CoV nucleocapsid (N protein. According to previous deletion analyses, M self-assembly involves multiple M sequence regions. To identify important M amino acid residues for VLP assembly, we coexpressed N with multiple M mutants containing substitution mutations at the amino-terminal ectodomain, carboxyl-terminal endodomain, or transmembrane segments. Our results indicate that a dileucine motif in the endodomain tail (218LL219 is required for efficient N packaging into VLPs. Results from cross-linking VLP analyses suggest that the cysteine residues 63, 85 and 158 are not in close proximity to the M dimer interface. We noted a significant reduction in M secretion due to serine replacement for C158, but not for C63 or C85. Further analysis suggests that C158 is involved in M-N interaction. In addition to mutations of the highly conserved 107-SWWSFNPE-114 motif, substitutions at codons W19, W57, P58, W91, Y94 or F95 all resulted in significantly reduced VLP yields, largely due to defective M secretion. VLP production was not significantly affected by a tryptophan replacement of Y94 or F95 or a phenylalanine replacement of W19, W57 or W91. Combined, these results indicate the involvement of specific M amino acids during SARS-CoV virus assembly, and suggest that aromatic residue retention at specific positions is critical for M function in terms of directing virus assembly.

  2. SARSvirus jumps species

    Indian Academy of Sciences (India)

    SARSvirus jumps species. Coronavirus reshuffles genes; Rotteir et al, Rotterdam showed the virus to jump from cats to mouse cells after single gene mutation ? Human disease due to virus jumping from wild or domestic animals; Present favourite animal - the cat; - edible or domestic.

  3. Abundant SAR11 viruses in the ocean.

    Science.gov (United States)

    Zhao, Yanlin; Temperton, Ben; Thrash, J Cameron; Schwalbach, Michael S; Vergin, Kevin L; Landry, Zachary C; Ellisman, Mark; Deerinck, Tom; Sullivan, Matthew B; Giovannoni, Stephen J

    2013-02-21

    Several reports proposed that the extraordinary dominance of the SAR11 bacterial clade in ocean ecosystems could be a consequence of unusual mechanisms of resistance to bacteriophage infection, including 'cryptic escape' through reduced cell size and/or K-strategist defence specialism. Alternatively, the evolution of high surface-to-volume ratios coupled with minimal genomes containing high-affinity transporters enables unusually efficient metabolism for oxidizing dissolved organic matter in the world's oceans that could support vast population sizes despite phage susceptibility. These ideas are important for understanding plankton ecology because they emphasize the potentially important role of top-down mechanisms in predation, thus determining the size of SAR11 populations and their concomitant role in biogeochemical cycling. Here we report the isolation of diverse SAR11 viruses belonging to two virus families in culture, for which we propose the name 'pelagiphage', after their host. Notably, the pelagiphage genomes were highly represented in marine viral metagenomes, demonstrating their importance in nature. One of the new phages, HTVC010P, represents a new podovirus subfamily more abundant than any seen previously, in all data sets tested, and may represent one of the most abundant virus subfamilies in the biosphere. This discovery disproves the theory that SAR11 cells are immune to viral predation and is consistent with the interpretation that the success of this highly abundant microbial clade is the result of successfully evolved adaptation to resource competition.

  4. Clipboard: Severe acute respiratory syndrome (SARS): an old virus ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 28; Issue 4. Clipboard: Severe acute respiratory syndrome (SARS): an old virus jumping into a new host or a new creation? M S Shaila. Volume 28 Issue 4 June 2003 pp 359-360. Fulltext. Click here to view fulltext PDF. Permanent link:

  5. The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

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    McBride, Ruth; Fielding, Burtram C.

    2012-01-01

    A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The subsequent efficient human-to-human transmission of this virus eventually affected more than 30 countries worldwide, resulting in a mortality rate of ~10% of infected individuals. The spread of the virus was ultimately controlled by isolation of infected individuals and there has been no infections reported since April 2004. However, the natural reservoir of the virus was never identified and it is not known if this virus will re-emerge and, therefore, research on this virus continues. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies. PMID:23202509

  6. Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response.

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    Li, Yan; Chen, Ming; Cao, Hongwei; Zhu, Yuanfeng; Zheng, Jiang; Zhou, Hong

    2013-02-01

    A dangerous cytokine storm occurs in the SARS involving in immune disorder, but many aspects of the pathogenetic mechanism remain obscure since its outbreak. To deeply reveal the interaction of host and SARS-CoV, based on the basic structural feature of pathogen-associated molecular pattern, we created a new bioinformatics method for searching potential pathogenic molecules and identified a set of SARS-CoV specific GU-rich ssRNA fragments with a high-density distribution in the genome. In vitro experiments, the result showed the representative SARS-CoV ssRNAs had powerful immunostimulatory activities to induce considerable level of pro-inflammatory cytokine TNF-a, IL-6 and IL-12 release via the TLR7 and TLR8, almost 2-fold higher than the strong stimulatory ssRNA40 that was found previously from other virus. Moreover, SARS-CoV ssRNA was able to cause acute lung injury in mice with a high mortality rate in vivo experiment. It suggests that SARS-CoV specific GU-rich ssRNA plays a very important role in the cytokine storm associated with a dysregulation of the innate immunity. This study not only presents new evidence about the immunopathologic damage caused by overactive inflammation during the SARS-CoV infection, but also provides a useful clue for a new therapeutic strategy. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  7. Cleavage of the SARS coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro.

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    Yiu-Wing Kam

    Full Text Available BACKGROUND: Entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native full-length S-protein trimer (triSpike of the severe acute respiratory syndrome coronavirus (SARS-CoV to cleavage by various airway proteases. METHODOLOGY/PRINCIPAL FINDINGS: PURIFIED TRISPIKE PROTEINS WERE READILY CLEAVED IN VITRO BY THREE DIFFERENT AIRWAY PROTEASES: trypsin, plasmin and TMPRSS11a. High Performance Liquid Chromatography (HPLC and amino acid sequencing analyses identified two arginine residues (R667 and R797 as potential protease cleavage site(s. The effect of protease-dependent enhancement of SARS-CoV infection was demonstrated with ACE2 expressing human bronchial epithelial cells 16HBE. Airway proteases regulate the infectivity of SARS-CoV in a fashion dependent on previous receptor binding. The role of arginine residues was further shown with mutant constructs (R667A, R797A or R797AR667A. Mutation of R667 or R797 did not affect the expression of S-protein but resulted in a differential efficacy of pseudotyping into SARS-CoVpp. The R667A SARS-CoVpp mutant exhibited a lack of virus entry enhancement following protease treatment. CONCLUSIONS/SIGNIFICANCE: These results suggest that SARS S-protein is susceptible to airway protease cleavage and, furthermore, that protease mediated enhancement of virus entry depends on specific conformation of SARS S-protein upon ACE2 binding. These data have direct implications for the cell entry mechanism of SARS-CoV along the respiratory system and, furthermore expand the possibility of identifying potential therapeutic agents against SARS-CoV.

  8. Coronavirus 3CL(pro) proteinase cleavage sites: Possible relevance to SARS virus pathology

    DEFF Research Database (Denmark)

    Kiemer, Lars; Lund, Ole; Brunak, Søren

    2004-01-01

    Background: Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS), efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like...... the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection....... Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. Results: We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network...

  9. RECOVIR Software for Identifying Viruses

    Science.gov (United States)

    Chakravarty, Sugoto; Fox, George E.; Zhu, Dianhui

    2013-01-01

    Most single-stranded RNA (ssRNA) viruses mutate rapidly to generate a large number of strains with highly divergent capsid sequences. Determining the capsid residues or nucleotides that uniquely characterize these strains is critical in understanding the strain diversity of these viruses. RECOVIR (an acronym for "recognize viruses") software predicts the strains of some ssRNA viruses from their limited sequence data. Novel phylogenetic-tree-based databases of protein or nucleic acid residues that uniquely characterize these virus strains are created. Strains of input virus sequences (partial or complete) are predicted through residue-wise comparisons with the databases. RECOVIR uses unique characterizing residues to identify automatically strains of partial or complete capsid sequences of picorna and caliciviruses, two of the most highly diverse ssRNA virus families. Partition-wise comparisons of the database residues with the corresponding residues of more than 300 complete and partial sequences of these viruses resulted in correct strain identification for all of these sequences. This study shows the feasibility of creating databases of hitherto unknown residues uniquely characterizing the capsid sequences of two of the most highly divergent ssRNA virus families. These databases enable automated strain identification from partial or complete capsid sequences of these human and animal pathogens.

  10. Reverse Genetics of SARS-Related Coronavirus Using Vaccinia Virus-Based Recombination

    Science.gov (United States)

    Zevenhoven, Jessika C.; Weber, Friedemann; Züst, Roland; Kuri, Thomas; Dijkman, Ronald; Chang, Guohui; Siddell, Stuart G.; Snijder, Eric J.; Thiel, Volker; Davidson, Andrew D.

    2012-01-01

    Severe acute respiratory syndrome (SARS) is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV) that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime) as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV). Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs). In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E). Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs. PMID:22412934

  11. Reverse genetics of SARS-related coronavirus using vaccinia virus-based recombination.

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    Sjoerd H E van den Worm

    Full Text Available Severe acute respiratory syndrome (SARS is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV. Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs. In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E. Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs.

  12. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.

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    I-Chueh Huang

    2011-01-01

    Full Text Available Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3 are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV hemagglutinin (HA protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2 of Marburg and Ebola filoviruses (MARV, EBOV. Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV and entry mediated by the SARS-CoV spike (S protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

  13. Severe Acute Respiratory Syndrome- SARS

    Indian Academy of Sciences (India)

    Table of contents. Severe Acute Respiratory Syndrome- SARS · PowerPoint Presentation · Slide 3 · Global pattern of SARS epidemic · Slide 5 · SARS – clinical features ... SARS virus · SARS – Koch´Postulates proved. SARSvirus jumps species · How infectious is SARS virus · SARS – Global Distribution- 10th July 2003.

  14. Potent Human Monoclonal Antibodies against SARS CoV, Nipah and Hendra Viruses

    Science.gov (United States)

    Prabakaran, Ponraj; Zhongyu, Zhu; Xiao, Xiaodong; Biragyn, Arya; Dimitrov, Antony S.; Broder, Christopher C.; Dimitrov, Dimiter S.

    2009-01-01

    Polyclonal antibodies have a century-old history of being effective against some viruses; recently, monoclonal antibodies (mAbs) have also shown success. The humanized mAb Synagis (palivizumab) remains still the only mAb against respiratory syncytial virus (RSV) infections approved by the U.S. Food and Drug Administration (FDA). Recently, several potent human monoclonal antibodies (hmAbs) targeting the Severe Acute Respiratory Syndrome-Associated coronavirus (SARS CoV) S glycoproteins were developed quickly after the virus was identified in 2003. Among these antibodies, m396 and S230.15 exhibit exceptional potency and cross-reactivity as they neutralize isolates from the first and second outbreaks and from palm civets both in vitroand in mice. Similarly, the first fully hmAbs against two other paramyxoviruses, Hendra virus (HeV) and Nipah virus (NiV), which can cause up to 75% mortality, were recently developed; one of them, m102.4, shows exceptional cross-reactive potency against both NiV and HeV. Three-dimensional molecular structures of envelope glycoproteins from these viruses in complexes with antibodies and/or receptors were recently determined. Structural analyses along with other experiments have provided insights into the molecular mechanisms of receptor recognition and antibody neutralization, and suggested that these antibodies alone or in combination could successfully fight the viruses’ heterogeneity and mutability which is a major problem in the development of effective therapeutic agents against viruses, including therapeutic antibodies. PMID:19216624

  15. Coronavirus 3CLpro proteinase cleavage sites: Possible relevance to SARS virus pathology

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    Blom Nikolaj

    2004-06-01

    Full Text Available Abstract Background Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS, efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. Results We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR, transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. Conclusions Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website: http://www.cbs.dtu.dk/services/NetCorona/.

  16. Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination.

    Science.gov (United States)

    Otter, J A; Donskey, C; Yezli, S; Douthwaite, S; Goldenberg, S D; Weber, D J

    2016-03-01

    Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  17. Challenges presented by MERS corona virus, and SARS corona virus to global health.

    Science.gov (United States)

    Al-Hazmi, Ali

    2016-07-01

    Numerous viral infections have arisen and affected global healthcare facilities. Millions of people are at severe risk of acquiring several evolving viral infections through several factors. In the present article we have described about risk factors, chance of infection, and prevention methods of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV), human coronaviruses (CoVs) frequently cause a normal cold which is mild and self-restricting. Zoonotic transmission of CoVs such as the newly discovered MERS-CoV and SARS-CoV, may be associated with severe lower respiratory tract infection. The present review provides the recent clinical and pathological information on MERS and SARS. The task is to transform these discoveries about MERS and SARS pathogenesis and to develop intervention methods that will eventually allow the effective control of these recently arising severe viral infections. Global health sector has learnt many lessons through the recent outbreak of MERS and SARS, but the need for identifying new antiviral treatment was not learned. In the present article we have reviewed the literature on the several facets like transmission, precautions and effectiveness of treatments used in patients with MERS-CoV and SARS infections.

  18. How Change of Public Transportation Usage Reveals Fear of the SARS Virus in a City

    Science.gov (United States)

    Wang, Kuo-Ying

    2014-01-01

    The outbreaks of the severe acute respiratory syndrome (SARS) epidemic in 2003 resulted in unprecedented impacts on people's daily life. One of the most significant impacts to people is the fear of contacting the SARS virus while engaging daily routine activity. Here we use data from daily underground ridership in Taipei City and daily reported new SARS cases in Taiwan to model the dynamics of the public fear of the SARS virus during the wax and wane of the SARS period. We found that for each reported new SARS case there is an immediate loss of about 1200 underground ridership (the fresh fear). These daily loss rates dissipate to the following days with an e-folding time of about 28 days, reflecting the public perception on the risk of contacting SARS virus when traveling with the underground system (the residual fear). About 50% of daily ridership was lost during the peak of the 2003 SARS period, compared with the loss of 80% daily ridership during the closure of the underground system after Typhoon Nari, the loss of 50–70% ridership due to the closure of the governmental offices and schools during typhoon periods, and the loss of 60% daily ridership during Chinese New Year holidays. PMID:24647278

  19. How change of public transportation usage reveals fear of the SARS virus in a city.

    Science.gov (United States)

    Wang, Kuo-Ying

    2014-01-01

    The outbreaks of the severe acute respiratory syndrome (SARS) epidemic in 2003 resulted in unprecedented impacts on people's daily life. One of the most significant impacts to people is the fear of contacting the SARS virus while engaging daily routine activity. Here we use data from daily underground ridership in Taipei City and daily reported new SARS cases in Taiwan to model the dynamics of the public fear of the SARS virus during the wax and wane of the SARS period. We found that for each reported new SARS case there is an immediate loss of about 1200 underground ridership (the fresh fear). These daily loss rates dissipate to the following days with an e-folding time of about 28 days, reflecting the public perception on the risk of contacting SARS virus when traveling with the underground system (the residual fear). About 50% of daily ridership was lost during the peak of the 2003 SARS period, compared with the loss of 80% daily ridership during the closure of the underground system after Typhoon Nari, the loss of 50-70% ridership due to the closure of the governmental offices and schools during typhoon periods, and the loss of 60% daily ridership during Chinese New Year holidays.

  20. A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Hugh D.; Eisfeld, Amie J.; Sims, Amy; McDermott, Jason E.; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Tilton, Susan C.; Tchitchek, Nicholas; Josset, Laurence; Li, Chengjun; Ellis, Amy L.; Chang, Jean H.; Heegel, Robert A.; Luna, Maria L.; Schepmoes, Athena A.; Shukla, Anil K.; Metz, Thomas O.; Neumann, Gabriele; Benecke, Arndt; Smith, Richard D.; Baric, Ralph; Kawaoka, Yoshihiro; Katze, Michael G.; Waters, Katrina M.

    2013-07-25

    Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel “crowd-based” approach to identify and combine ranking metrics that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse ‘omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models.

  1. Induction of neutralising antibodies and cellular immune responses against SARS coronavirus by recombinant measles viruses.

    Science.gov (United States)

    Liniger, Matthias; Zuniga, Armando; Tamin, Azaibi; Azzouz-Morin, Teldja N; Knuchel, Marlyse; Marty, Rene R; Wiegand, Marian; Weibel, Sara; Kelvin, David; Rota, Paul A; Naim, Hussein Y

    2008-04-16

    Live attenuated recombinant measles viruses (rMV) expressing a codon-optimised spike glycoprotein (S) or nucleocapsid protein (N) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were generated (rMV-S and rMV-N). Both recombinant viruses stably expressed the corresponding SARS-CoV proteins, grew to similar end titres as the parental strain and induced high antibody titres against MV and the vectored SARS-CoV antigens (S and N) in transgenic mice susceptible to measles infection. The antibodies induced by rMV-S had a high neutralising effect on SARS-CoV as well as on MV. Moreover, significant N-specific cellular immune responses were measured by IFN-gamma ELISPOT assays. The pre-existence of anti-MV antibodies induced by the initial immunisation dose did not inhibit boost of anti-S and anti-N antibodies. Immunisations comprising a mixture of rMV-S and rMV-N induced immune responses similar in magnitude to that of vaccine components administered separately. These data support the suitability of MV as a bivalent candidate vaccine vector against MV and emerging viruses such as SARS-CoV.

  2. Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV

    Science.gov (United States)

    Liu, Ye V.; Massare, Michael J.; Barnard, Dale L.; Kort, Thomas; Nathan, Margret; Wang, Lei; Smith, Gale

    2011-01-01

    SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents. PMID:21762752

  3. Relationship of SARS-CoV to other pathogenic RNA viruses explored by tetranucleotide usage profiling

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    Danchin Antoine

    2003-09-01

    Full Text Available Abstract Background The exact origin of the cause of the Severe Acute Respiratory Syndrome (SARS is still an open question. The genomic sequence relationship of SARS-CoV with 30 different single-stranded RNA (ssRNA viruses of various families was studied using two non-standard approaches. Both approaches began with the vectorial profiling of the tetra-nucleotide usage pattern V for each virus. In approach one, a distance measure of a vector V, based on correlation coefficient was devised to construct a relationship tree by the neighbor-joining algorithm. In approach two, a multivariate factor analysis was performed to derive the embedded tetra-nucleotide usage patterns. These patterns were subsequently used to classify the selected viruses. Results Both approaches yielded relationship outcomes that are consistent with the known virus classification. They also indicated that the genome of RNA viruses from the same family conform to a specific pattern of word usage. Based on the correlation of the overall tetra-nucleotide usage patterns, the Transmissible Gastroenteritis Virus (TGV and the Feline CoronaVirus (FCoV are closest to SARS-CoV. Surprisingly also, the RNA viruses that do not go through a DNA stage displayed a remarkable discrimination against the CpG and UpA di-nucleotide (z = -77.31, -52.48 respectively and selection for UpG and CpA (z = 65.79,49.99 respectively. Potential factors influencing these biases are discussed. Conclusion The study of genomic word usage is a powerful method to classify RNA viruses. The congruence of the relationship outcomes with the known classification indicates that there exist phylogenetic signals in the tetra-nucleotide usage patterns, that is most prominent in the replicase open reading frames.

  4. Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections

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    Müller Marcel A

    2005-02-01

    Full Text Available Abstract Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.

  5. Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion

    Science.gov (United States)

    Simmons, Graham; Bertram, Stephanie; Glowacka, Ilona; Steffen, Imke; Chaipan, Chawaree; Agudelo, Juliet; Lu, Kai; Rennekamp, Andrew J.; Hofmann, Heike; Bates, Paul; Pöhlmann, Stefan

    2011-01-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) poses a considerable threat to human health. Activation of the viral spike (S)-protein by host cell proteases is essential for viral infectivity. However, the cleavage sites in SARS-S and the protease(s) activating SARS-S are incompletely defined. We found that R667 was dispensable for SARS-S-driven virus-cell fusion and for SARS-S-activation by trypsin and cathepsin L in a virus-virus fusion assay. Mutation T760R, which optimizes the minimal furin consensus motif 758-RXXR-762, and furin overexpression augmented SARS-S-activity, but did not result in detectable SARS-S cleavage. Finally, SARS-S-driven cell-cell fusion was independent of cathepsin L, a protease essential for virus-cell fusion. Instead, a so far unknown leupeptin-sensitive host cell protease activated cellular SARS-S for fusion with target cells expressing high levels of ACE2. Thus, different host cell proteases activate SARS-S for virus-cell and cell-cell fusion and SARS-S cleavage at R667 and 758-RXXR-762 can be dispensable for SARS-S activation. PMID:21435673

  6. SARS-CoV envelope protein palmitoylation or nucleocapid association is not required for promoting virus-like particle production.

    Science.gov (United States)

    Tseng, Ying-Tzu; Wang, Shiu-Mei; Huang, Kuo-Jung; Wang, Chin-Tien

    2014-04-27

    Coronavirus membrane (M) proteins are capable of interacting with nucleocapsid (N) and envelope (E) proteins. Severe acute respiratory syndrome coronavirus (SARS-CoV) M co-expression with either N or E is sufficient for producing virus-like particles (VLPs), although at a lower level compared to M, N and E co-expression. Whether E can release from cells or E/N interaction exists so as to contribute to enhanced VLP production is unknown. It also remains to be determined whether E palmitoylation or disulfide bond formation plays a role in SARS-CoV virus assembly. SARS-CoV N is released from cells through an association with E protein-containing vesicles. Further analysis suggests that domains involved in E/N interaction are largely located in both carboxyl-terminal regions. Changing all three E cysteine residues to alanines did not exert negative effects on E release, E association with N, or E enhancement of VLP production, suggesting that E palmitoylation modification or disulfide bond formation is not required for SARS-CoV virus assembly. We found that removal of the last E carboxyl-terminal residue markedly affected E release, N association, and VLP incorporation, but did not significantly compromise the contribution of E to efficient VLP production. The independence of the SARS-CoV E enhancement effect on VLP production from its viral packaging capacity suggests a distinct SARS-CoV E role in virus assembly.

  7. The structure of a rigorously conserved RNA element within the SARS virus genome.

    Directory of Open Access Journals (Sweden)

    Michael P Robertson

    2005-01-01

    Full Text Available We have solved the three-dimensional crystal structure of the stem-loop II motif (s2m RNA element of the SARS virus genome to 2.7-A resolution. SARS and related coronaviruses and astroviruses all possess a motif at the 3' end of their RNA genomes, called the s2m, whose pathogenic importance is inferred from its rigorous sequence conservation in an otherwise rapidly mutable RNA genome. We find that this extreme conservation is clearly explained by the requirement to form a highly structured RNA whose unique tertiary structure includes a sharp 90 degrees kink of the helix axis and several novel longer-range tertiary interactions. The tertiary base interactions create a tunnel that runs perpendicular to the main helical axis whose interior is negatively charged and binds two magnesium ions. These unusual features likely form interaction surfaces with conserved host cell components or other reactive sites required for virus function. Based on its conservation in viral pathogen genomes and its absence in the human genome, we suggest that these unusual structural features in the s2m RNA element are attractive targets for the design of anti-viral therapeutic agents. Structural genomics has sought to deduce protein function based on three-dimensional homology. Here we have extended this approach to RNA by proposing potential functions for a rigorously conserved set of RNA tertiary structural interactions that occur within the SARS RNA genome itself. Based on tertiary structural comparisons, we propose the s2m RNA binds one or more proteins possessing an oligomer-binding-like fold, and we suggest a possible mechanism for SARS viral RNA hijacking of host protein synthesis, both based upon observed s2m RNA macromolecular mimicry of a relevant ribosomal RNA fold.

  8. Super-spreaders and the rate of transmission of the SARS virus

    Science.gov (United States)

    Small, Michael; Tse, C. K.; Walker, David M.

    2006-03-01

    We describe a stochastic small-world network model of transmission of the SARS virus. Unlike the standard Susceptible-Infected-Removed models of disease transmission, our model exhibits both geographically localised outbreaks and “super-spreaders”. Moreover, the combination of localised and long range links allows for more accurate modelling of partial isolation and various public health policies. From this model, we derive an expression for the probability of a widespread outbreak and a condition to ensure that the epidemic is controlled. Moreover, multiple simulations are used to make predictions of the likelihood of various eventual scenarios for fixed initial conditions. The main conclusions of this study are: (i) “super-spreaders” may occur even if the infectiousness of all infected individuals is constant; (ii) consistent with previous reports, extended exposure time beyond 3-5 days (i.e. significant nosocomial transmission) was the key factor in the severity of the SARS outbreak in Hong Kong; and, (iii) the spread of SARS can be effectively controlled by either limiting long range links (imposing a partial quarantine) or enforcing rapid hospitalisation and isolation of symptomatic individuals.

  9. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

    Science.gov (United States)

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-04-22

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)*

    Science.gov (United States)

    Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

    2016-01-01

    Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm. Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. PMID:26953343

  11. Antimicrobial activity of phenolic compounds identified in wild mushrooms, SAR analysis and docking studies.

    Science.gov (United States)

    Alves, M J; Ferreira, I C F R; Froufe, H J C; Abreu, R M V; Martins, A; Pintado, M

    2013-08-01

    Although the antimicrobial activity of extracts from several mushroom species has been reported, studies with the individual compounds present in that extracts are scarce. Herein, the antimicrobial activity of different phenolic compounds identified and quantified in mushroom species from all over the world was evaluated. Furthermore, a structure-activity relationship (SAR) analysis and molecular docking studies were performed, in order to provide insights into the mechanism of action of potential antimicrobial drugs for resistant micro-organisms. 2,4-Dihydroxybenzoic and protocatechuic acids were the phenolic compounds with higher activity against the majority of Gram-negative and Gram-positive bacteria. Furthermore, phenolic compounds inhibited more MRSA than methicillin-susceptible Staphylococcus aureus. MRSA was inhibited by 2,4-dihydroxybenzoic, vanillic, syringic (MICs = 0.5 mg ml(-1) ) and p-coumaric (MIC = 1 mg ml(-1) ) acids, while these compounds at the same concentrations had no inhibitory effects against methicillin-susceptible Staph. aureus. The presence of carboxylic acid (COOH), two hydroxyl (OH) groups in para and ortho positions of the benzene ring and also a methoxyl (OCH3 ) group in the meta position seems to be important for anti-MRSA activity. Phenolic compounds could be used as antimicrobial agents, namely against some micro-organisms resistant to commercial antibiotics. © 2013 The Society for Applied Microbiology.

  12. Identifying Hendra virus diversity in pteropid bats.

    Directory of Open Access Journals (Sweden)

    Ina Smith

    Full Text Available Hendra virus (HeV causes a zoonotic disease with high mortality that is transmitted to humans from bats of the genus Pteropus (flying foxes via an intermediary equine host. Factors promoting spillover from bats to horses are uncertain at this time, but plausibly encompass host and/or agent and/or environmental factors. There is a lack of HeV sequence information derived from the natural bat host, as previously sequences have only been obtained from horses or humans following spillover events. In order to obtain an insight into possible variants of HeV circulating in flying foxes, collection of urine was undertaken in multiple flying fox roosts in Queensland, Australia. HeV was found to be geographically widespread in flying foxes with a number of HeV variants circulating at the one time at multiple locations, while at times the same variant was found circulating at disparate locations. Sequence diversity within variants allowed differentiation on the basis of nucleotide changes, and hypervariable regions in the genome were identified that could be used to differentiate circulating variants. Further, during the study, HeV was isolated from the urine of flying foxes on four occasions from three different locations. The data indicates that spillover events do not correlate with particular HeV isolates, suggesting that host and/or environmental factors are the primary determinants of bat-horse spillover. Thus future spillover events are likely to occur, and there is an on-going need for effective risk management strategies for both human and animal health.

  13. Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing

    Science.gov (United States)

    Eckerle, Lance D.; Becker, Michelle M.; Halpin, Rebecca A.; Li, Kelvin; Venter, Eli; Lu, Xiaotao; Scherbakova, Sana; Graham, Rachel L.; Baric, Ralph S.; Stockwell, Timothy B.; Spiro, David J.; Denison, Mark R.

    2010-01-01

    Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and

  14. Structures and Polymorphic Interactions of Two Heptad-Repeat Regions of the SARS Virus S2 Protein

    Energy Technology Data Exchange (ETDEWEB)

    Deng,Y.; Liu, J.; Zheng, Q.; Yong, W.; Lu, M.

    2006-01-01

    Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct a-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.

  15. Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

    Directory of Open Access Journals (Sweden)

    Denong Wang

    2015-03-01

    Full Text Available Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA, for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV, and human cytomegalovirus (HCMV. In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn. These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.

  16. Anti-SARS coronavirus agents: a patent review (2008 - present).

    Science.gov (United States)

    Kumar, Vathan; Jung, Young-Sik; Liang, Po-Huang

    2013-10-01

    A novel coronavirus (CoV), unlike previous typical human coronaviruses (HCoVs), was identified as causative agent for severe acute respiratory syndrome (SARS). SARS first surfaced as a pandemic in late 2002 and originated in southern China. SARS-CoV rapidly spread to > 30 countries by 2003, infecting nearly 8,000 people and causing around 800 fatalities. After 10 years of silence, a 2012 report alarmed researchers about the emergence of a new strain of CoV causing SARS-like disease. To combat SARS, scientists applied for patents on various therapeutic agents, including small-molecule inhibitors targeting the essential proteases, helicase and other proteins of the virus, natural products, approved drugs, molecules binding to the virus, neutralizing antibodies, vaccines, anti-sense RNA, siRNA and ribozyme against SARS-CoV. In this article, the patents published from 2008 to the present for the new therapeutics that could potentially be used in the prophylaxis and treatment of SARS are reviewed. The therapeutic interventions or prophylaxis discussed in this review seems to offer promising solutions to tackle SARS. Rather than being complacent about the results, we should envisage how to transform them into drug candidates that may be useful in combating SARS and related viral infections in the future.

  17. SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon.

    Science.gov (United States)

    Totura, Allison L; Baric, Ralph S

    2012-06-01

    SARS-CoV is a pathogenic coronavirus that emerged from a zoonotic reservoir, leading to global dissemination of the virus. The association SARS-CoV with aberrant cytokine, chemokine, and Interferon Stimulated Gene (ISG) responses in patients provided evidence that SARS-CoV pathogenesis is at least partially controlled by innate immune signaling. Utilizing models for SARS-CoV infection, key components of innate immune signaling pathways have been identified as protective factors against SARS-CoV disease, including STAT1 and MyD88. Gene transcription signatures unique to SARS-CoV disease states have been identified, but host factors that regulate exacerbated disease phenotypes still remain largely undetermined. SARS-CoV encodes several proteins that modulate innate immune signaling through the antagonism of the induction of Interferon and by avoidance of ISG effector functions. Copyright © 2012. Published by Elsevier B.V.

  18. A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication

    Energy Technology Data Exchange (ETDEWEB)

    Ratia, Kiira; Pegan, Scott; Takayama, Jun; Sleeman, Katrina; Coughlin, Melissa; Baliji, Surendranath; Chaudhuri, Rima; Fu, Wentao; Prabhakar, Bellur S.; Johnson, Michael E.; Baker, Susan C.; Ghosh, Arun K.; Mesecar, Andrew D. (Loyola); (Purdue); (UIC)

    2008-10-27

    We report the discovery and optimization of a potent inhibitor against the papain-like protease (PLpro) from the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). This unique protease is not only responsible for processing the viral polyprotein into its functional units but is also capable of cleaving ubiquitin and ISG15 conjugates and plays a significant role in helping SARS-CoV evade the human immune system. We screened a structurally diverse library of 50,080 compounds for inhibitors of PLpro and discovered a noncovalent lead inhibitor with an IC{sub 50} value of 20 {mu}M, which was improved to 600 nM via synthetic optimization. The resulting compound, GRL0617, inhibited SARS-CoV viral replication in Vero E6 cells with an EC{sub 50} of 15 {mu}M and had no associated cytotoxicity. The X-ray structure of PLpro in complex with GRL0617 indicates that the compound has a unique mode of inhibition whereby it binds within the S4-S3 subsites of the enzyme and induces a loop closure that shuts down catalysis at the active site. These findings provide proof-of-principle that PLpro is a viable target for development of antivirals directed against SARS-CoV, and that potent noncovalent cysteine protease inhibitors can be developed with specificity directed toward pathogenic deubiquitinating enzymes without inhibiting host DUBs.

  19. Tomato chlorotic spot virus Identified in Marsdenia floribunda in Florida

    Science.gov (United States)

    Ornamental crops including hoya, annual vinca and portulaca have recently been identified with Tomato chlorotic spot virus (TCSV) infections in Florida. Observations of Marsdenia floribunda, commonly known as Madagascar jasmine, in September 2016 revealed TCSV-like symptoms. Testing of these sympt...

  20. Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model

    Science.gov (United States)

    Cameron, Mark J.; Kelvin, Alyson A.; Leon, Alberto J.; Cameron, Cheryl M.; Ran, Longsi; Xu, Luoling; Chu, Yong-Kyu; Danesh, Ali; Fang, Yuan; Li, Qianjun; Anderson, Austin; Couch, Ronald C.; Paquette, Stephane G.; Fomukong, Ndingsa G.; Kistner, Otfried; Lauchart, Manfred; Rowe, Thomas; Harrod, Kevin S.; Jonsson, Colleen B.; Kelvin, David J.

    2012-01-01

    In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)3-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines. PMID:23029269

  1. Identifying Successive Eruption of Guntur Volcanic Complex Using Magnetic Susceptibility and Polarimetric Synthetic Aperture Radar (PolSAR) Data

    Science.gov (United States)

    Saepuloh, Asep; Bakker, Erwin

    2017-06-01

    Identifying distribution and stratigraphic of volcanic products are important not only for mitigating volcanic hazards, but also to know the characteristics of the successive eruptions. Guntur volcanic complex located in Garut, West Java, Indonesia was selected as study area because of the last eruption took place in 1847 and the volcanic activity has been dormant since then, however its seismicity is still active. During the period of July to October 2009, the hypocentre distribution of volcano tectonic earthquakes is mostly located at western flank of the volcano, beneath Guntur - Gandapura craters at the depth of less than 5 km. This study is aimed to identify distribution and succession of volcanic products based on their magnetic properties and backscattering signal of Polarimetric Synthetic Aperture Radar (PolSAR) data. The polarimetric decomposition method was used to identify the distribution of the volcanic products based on their scattering characteristics. Then, the field measurement using SM-30 magnetic susceptibility meter was performed to confirm the units of volcanic products and interpret their successions. According to the polarimetric decomposition method, we could identify fifteen successive eruptions formed Guntur Volcano Complex and termed as Khuluk and Gumuk in Indonesian standard. The successions were produced Gumuk Windu, Gumuk Malang, Gumuk Pulus, Gumuk Putrri, Khuluk Meungpeuk, Gumuk Cakra, Gumuk Gandapura, Gumuk Putri, Gumuk Gajah, Gumuk Batususun, Khuluk Pasirlaku, Gumuk Agung, Gumuk Picung, Gumuk Pasirmalang, Gumuk Masigit, Khuluk Kabuyutan and Khuluk Guntur. The magnetic susceptibility confirmed that the variations of magnetic susceptibility of rocks at each gumuk agreed with their stratigraphy.

  2. Bats and SARS

    Centers for Disease Control (CDC) Podcasts

    2006-11-08

    Bats are a natural reservoir for emerging viruses, among them henipaviruses and rabies virus variants. Dr. Nina Marano, Chief, Geographic Medicine and Health Promotion Branch, Division of Global Migration and Quarantine, CDC, explains connection between horseshoe bats and SARS coronavirus transmission.  Created: 11/8/2006 by Emerging Infectious Diseases.   Date Released: 11/17/2006.

  3. Macromolecular Antiviral Agents against Zika, Ebola, SARS, and Other Pathogenic Viruses

    DEFF Research Database (Denmark)

    Schandock, Franziska; Riber, Camilla Frich; Röcker, Annika

    2017-01-01

    . This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses. Results presented herein offer structure...

  4. DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY HEPATITIS E VIRUS

    Science.gov (United States)

    Hepatitis E virus (HEV) is a waterborne emerging pathogen that causes significant illness in the developing world. Thus far, an HEV outbreak has not been reported in the U.S., although a swine variant of the virus is common in Midwestern hogs. Because viruses isolated from two ...

  5. Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus

    OpenAIRE

    Josset, Laurence; Menachery, Vineet D.; Gralinski, Lisa E.; Agnihothram, Sudhakar; Sova, Pavel; Carter, Victoria S.; Yount, Boyd L.; Graham, Rachel L.; Baric, Ralph S.; Katze, Michael G.

    2013-01-01

    ABSTRACT A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was abl...

  6. Identifying Active Faults by Improving Earthquake Locations with InSAR Data and Bayesian Estimation: The 2004 Tabuk (Saudi Arabia) Earthquake Sequence

    KAUST Repository

    Xu, Wenbin

    2015-02-03

    A sequence of shallow earthquakes of magnitudes ≤5.1 took place in 2004 on the eastern flank of the Red Sea rift, near the city of Tabuk in northwestern Saudi Arabia. The earthquakes could not be well located due to the sparse distribution of seismic stations in the region, making it difficult to associate the activity with one of the many mapped faults in the area and thus to improve the assessment of seismic hazard in the region. We used Interferometric Synthetic Aperture Radar (InSAR) data from the European Space Agency’s Envisat and ERS‐2 satellites to improve the location and source parameters of the largest event of the sequence (Mw 5.1), which occurred on 22 June 2004. The mainshock caused a small but distinct ∼2.7  cm displacement signal in the InSAR data, which reveals where the earthquake took place and shows that seismic reports mislocated it by 3–16 km. With Bayesian estimation, we modeled the InSAR data using a finite‐fault model in a homogeneous elastic half‐space and found the mainshock activated a normal fault, roughly 70 km southeast of the city of Tabuk. The southwest‐dipping fault has a strike that is roughly parallel to the Red Sea rift, and we estimate the centroid depth of the earthquake to be ∼3.2  km. Projection of the fault model uncertainties to the surface indicates that one of the west‐dipping normal faults located in the area and oriented parallel to the Red Sea is a likely source for the mainshock. The results demonstrate how InSAR can be used to improve locations of moderate‐size earthquakes and thus to identify currently active faults.

  7. SAR: Stroke Authorship Recognition

    KAUST Repository

    Shaheen, Sara

    2015-10-15

    Are simple strokes unique to the artist or designer who renders them? If so, can this idea be used to identify authorship or to classify artistic drawings? Also, could training methods be devised to develop particular styles? To answer these questions, we propose the Stroke Authorship Recognition (SAR) approach, a novel method that distinguishes the authorship of 2D digitized drawings. SAR converts a drawing into a histogram of stroke attributes that is discriminative of authorship. We provide extensive classification experiments on a large variety of data sets, which validate SAR\\'s ability to distinguish unique authorship of artists and designers. We also demonstrate the usefulness of SAR in several applications including the detection of fraudulent sketches, the training and monitoring of artists in learning a particular new style and the first quantitative way to measure the quality of automatic sketch synthesis tools. © 2015 The Eurographics Association and John Wiley & Sons Ltd.

  8. Guidelines for Identifying Homologous Recombination Events in Influenza A Virus

    NARCIS (Netherlands)

    Boni, M.F.; de Jong, M.D.; van Doorn, H.R.; Holmes, E.C.

    2010-01-01

    The rapid evolution of influenza viruses occurs both clonally and non-clonally through a variety of genetic mechanisms and selection pressures. The non-clonal evolution of influenza viruses comprises relatively frequent reassortment among gene segments and a more rarely reported process of

  9. Surface vimentin is critical for the cell entry of SARS-CoV.

    Science.gov (United States)

    Yu, Yvonne Ting-Chun; Chien, Ssu-Chia; Chen, I-Yin; Lai, Chia-Tsen; Tsay, Yeou-Guang; Chang, Shin C; Chang, Ming-Fu

    2016-01-22

    Severe acute respiratory syndrome coronavirus (SARS-CoV) caused a global panic due to its high morbidity and mortality during 2002 and 2003. Soon after the deadly disease outbreak, the angiotensin-converting enzyme 2 (ACE2) was identified as a functional cellular receptor in vitro and in vivo for SARS-CoV spike protein. However, ACE2 solely is not sufficient to allow host cells to become susceptible to SARS-CoV infection, and other host factors may be involved in SARS-CoV spike protein-ACE2 complex. A host intracellular filamentous cytoskeletal protein vimentin was identified by immunoprecipitation and LC-MS/MS analysis following chemical cross-linking on Vero E6 cells that were pre-incubated with the SARS-CoV spike protein. Moreover, flow cytometry data demonstrated an increase of the cell surface vimentin level by 16.5 % after SARS-CoV permissive Vero E6 cells were treated with SARS-CoV virus-like particles (VLPs). A direct interaction between SARS-CoV spike protein and host surface vimentin was further confirmed by far-Western blotting. In addition, antibody neutralization assay and shRNA knockdown experiments indicated a vital role of vimentin in cell binding and uptake of SARS-CoV VLPs and the viral spike protein. A direct interaction between vimentin and SARS-CoV spike protein during viral entry was observed. Vimentin is a putative anti-viral drug target for preventing/reducing the susceptibility to SARS-CoV infection.

  10. SARS: Down But Still a Threat

    Science.gov (United States)

    2003-08-01

    Diphtheria Tickborne Encephalitis E. coli 0157:H7 Avian Influenza SARS Nipah virus Japanese Encephalitis Hendra virus Lyssavirus Ross River Fever virus ...pandemic. When a new type of flu virus emerges from a reassortment of animal and human viruses to which humans have no prior immunity, a pandemic...utilized the World Health Organization’s (WHO) global network of research facilities to share data and speed the identification of the virus causing

  11. Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus.

    Science.gov (United States)

    Yasui, Fumihiko; Kohara, Michinori; Kitabatake, Masahiro; Nishiwaki, Tetsu; Fujii, Hideki; Tateno, Chise; Yoneda, Misako; Morita, Kouichi; Matsushima, Kouji; Koyasu, Shigeo; Kai, Chieko

    2014-04-01

    While the 2002-2003 outbreak of severe acute respiratory syndrome (SARS) resulted in 774 deaths, patients who were affected with mild pulmonary symptoms successfully recovered. The objective of the present work was to identify, using SARS coronavirus (SARS-CoV) mouse infection models, immune factors responsible for clearing of the virus. The elimination of pulmonary SARS-CoV infection required the activation of B cells by CD4(+) T cells. Furthermore, passive immunization (post-infection) with homologous (murine) anti-SARS-CoV antiserum showed greater elimination efficacy against SARS-CoV than that with heterologous (rabbit) antiserum, despite the use of equivalent titers of neutralizing antibodies. This distinction was mediated by mouse phagocytic cells (monocyte-derived infiltrating macrophages and partially alveolar macrophages, but not neutrophils), as demonstrated both by adoptive transfer from donors and by immunological depletion of selected cell types. These results indicate that the cooperation of anti-SARS-CoV antibodies and phagocytic cells plays an important role in the elimination of SARS-CoV. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The role of infections and coinfections with newly identified and emerging respiratory viruses in children

    Directory of Open Access Journals (Sweden)

    Debiaggi Maurizia

    2012-10-01

    Full Text Available Abstract Acute respiratory infections are a major cause of morbidity in children both in developed and developing countries. A wide range of respiratory viruses, including respiratory syncytial virus (RSV, influenza A and B viruses, parainfluenza viruses (PIVs, adenovirus, rhinovirus (HRV, have repeatedly been detected in acute lower respiratory tract infections (LRTI in children in the past decades. However, in the last ten years thanks to progress in molecular technologies, newly discovered viruses have been identified including human Metapneumovirus (hMPV, coronaviruses NL63 (HcoV-NL63 and HKU1 (HcoV-HKU1, human Bocavirus (HBoV, new enterovirus (HEV, parechovirus (HpeV and rhinovirus (HRV strains, polyomaviruses WU (WUPyV and KI (KIPyV and the pandemic H1N1v influenza A virus. These discoveries have heavily modified previous knowledge on respiratory infections mainly highlighting that pediatric population is exposed to a variety of viruses with similar seasonal patterns. In this context establishing a causal link between a newly identified virus and the disease as well as an association between mixed infections and an increase in disease severity can be challenging. This review will present an overview of newly recognized as well as the main emerging respiratory viruses and seek to focus on the their contribution to infection and co-infection in LRTIs in childhood.

  13. Data Analytics for SAR

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, David Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Calef, Matthew Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-02

    We assess the ability of variants of anomalous change detection (ACD) to identify human activity associated with large outdoor music festivals as they are seen from synthetic aperture radar (SAR) imagery collected by the Sentinel-1 satellite constellation. We found that, with appropriate feature vectors, ACD using random-forest machine learning was most effective at identifying changes associated with the human activity.

  14. A metagenomics and case-control study to identify viruses associated with bovine respiratory disease.

    Science.gov (United States)

    Ng, Terry Fei Fan; Kondov, Nikola O; Deng, Xutao; Van Eenennaam, Alison; Neibergs, Holly L; Delwart, Eric

    2015-05-01

    Bovine respiratory disease (BRD) is a common health problem for both dairy and beef cattle, resulting in significant economic loses. In order to identify viruses associated with BRD, we used a metagenomics approach to enrich and sequence viral nucleic acids in the nasal swabs of 50 young dairy cattle with symptoms of BRD. Following deep sequencing, de novo assembly, and translated protein sequence similarity searches, numerous known and previously uncharacterized viruses were identified. Bovine adenovirus 3, bovine adeno-associated virus, bovine influenza D virus, bovine parvovirus 2, bovine herpesvirus 6, bovine rhinitis A virus, and multiple genotypes of bovine rhinitis B virus were identified. The genomes of a previously uncharacterized astrovirus and picobirnaviruses were also partially or fully sequenced. Using real-time PCR, the rates of detection of the eight viruses that generated the most reads were compared for the nasal secretions of 50 animals with BRD versus 50 location-matched healthy control animals. Viruses were detected in 68% of BRD-affected animals versus 16% of healthy control animals. Thirty-eight percent of sick animals versus 8% of controls were infected with multiple respiratory viruses. Significantly associated with BRD were bovine adenovirus 3 (P metagenomics and real-time PCR detection approach in carefully matched cases and controls can provide a rapid means to identify viruses associated with a complex disease, paving the way for further confirmatory tests and ultimately to effective intervention strategies. Bovine respiratory disease is the most economically important disease affecting the cattle industry, whose complex root causes include environmental, genetics, and infectious factors. Using an unbiased metagenomics approach, we characterized the viruses in respiratory secretions from BRD cases and identified known and previously uncharacterized viruses belonging to seven viral families. Using a case-control format with location

  15. The aetiology of SARS: Koch's postulates fulfilled

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); T. Kuiken (Thijs)

    2004-01-01

    textabstractProof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) is the primary cause of severe acute respiratory syndrome (SARS) came from a series of studies on experimentally infected cynomolgus macaques (Macaca, fascicularis). SARS-CoV-infected

  16. The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus

    Energy Technology Data Exchange (ETDEWEB)

    McDermott, Jason E.; Mitchell, Hugh D.; Gralinski, Lisa E.; Eisfeld, Amie J.; Josset, Laurence; Bankhead, Armand; Neumann, Gabriele; Tilton, Susan C.; Schäfer, Alexandra; Li, Chengjun; Fan, Shufang; McWeeney, Shannon; Baric, Ralph S.; Katze, Michael G.; Waters, Katrina M.

    2016-09-23

    The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ antiimmune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine, tumor necrosis factor alpha (TNFα), promote pathogenesis through a parallel feed-forward circuit that promotes inflammation. These results are consistent with previous studies showing the role of over-stimulation of the inflammatory response to SARS-CoV in pathogenesis. We conclude that the critical balance between immune response and inflammation can be manipulated to improve the outcome of the infection. Further, our study provides two potential therapeutic strategies for mitigating the effects of SARS-CoV infection, and may provide insight into treatment strategies for Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

  17. Metagenomic analysis of viruses associated with field-grown and retail lettuce identifies human and animal viruses.

    Science.gov (United States)

    Aw, Tiong Gim; Wengert, Samantha; Rose, Joan B

    2016-04-16

    The emergence of culture- and sequence-independent metagenomic methods has not only provided great insight into the microbial community structure in a wide range of clinical and environmental samples but has also proven to be powerful tools for pathogen detection. Recent studies of the food microbiome have revealed the vast genetic diversity of bacteria associated with fresh produce. However, no work has been done to apply metagenomic methods to tackle viruses associated with fresh produce for addressing food safety. Thus, there is a little knowledge about the presence and diversity of viruses associated with fresh produce from farm-to-fork. To address this knowledge gap, we assessed viruses on commercial romaine and iceberg lettuces in fields and a produce distribution center using a shotgun metagenomic sequencing targeting both RNA and DNA viruses. Commercial lettuce harbors an immense assemblage of viruses that infect a wide range of hosts. As expected, plant pathogenic viruses dominated these communities. Sequences of rotaviruses and picobirnaviruses were also identified in both field-harvest and retail lettuce samples, suggesting an emerging foodborne transmission threat that has yet to be fully recognized. The identification of human and animal viruses in lettuce samples in the field emphasizes the importance of preventing viral contamination on leafy greens starting at the field. Although there are still some inherent experimental and bioinformatics challenges in applying viral metagenomic approaches for food safety testing, this work will facilitate further application of this unprecedented deep sequencing method to food samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Antiviral response in the nasopharynx identifies patients with respiratory virus infection.

    Science.gov (United States)

    Landry, Marie L; Foxman, Ellen F

    2017-12-21

    Despite the high burden of respiratory infection and the importance of early and accurate diagnosis, there is no simple diagnostic test to rule in viral infection as a cause of respiratory symptoms. We performed RNASeq on human nasal epithelial cells following stimulation of the intracellular viral recognition receptor RIG-I. Next, we evaluated whether measuring identified host mRNAs and proteins from patient nasopharyngeal swabs could predict the presence of a respiratory virus in the sample. Our first study showed that a signature of three mRNAs, CXCL10, IFIT2, and OASL, predicted respiratory virus detection with an accuracy of 97% (95% C.I. 0.9-1.0), and identified proteins correlating with virus detection. In a second study, elevated CXCL11 or CXCL10 protein levels identified samples containing respiratory viruses, including viruses not on the initial test panel. Overall AUCs were: CXCL11 AUC=0.901 (95% CI 0.86-0.94); CXCL10 AUC=0.85 (95%CI 0.80-0.91). Patients were primarily older adults or young children, reflecting the population tested for respiratory viruses in our healthcare system. Host antiviral mRNAs and single host proteins detectable using nasopharyngeal swabs accurately predict the presence of viral infection. This approach holds promise for developing rapid, cost-effective tests to improve management of patients with respiratory illnesses.

  19. Monkeypox Virus Host Factor Screen Using Haploid Cells Identifies Essential Role of GARP Complex in Extracellular Virus Formation.

    Science.gov (United States)

    Realegeno, Susan; Puschnik, Andreas S; Kumar, Amrita; Goldsmith, Cynthia; Burgado, Jillybeth; Sambhara, Suryaprakash; Olson, Victoria A; Carroll, Darin; Damon, Inger; Hirata, Tetsuya; Kinoshita, Taroh; Carette, Jan E; Satheshkumar, Panayampalli Subbian

    2017-06-01

    Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. We validated the role of a set of vacuolar protein sorting (VPS) genes during infection, VPS51 to VPS54 (VPS51-54), which comprise the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex involved in retrograde transport of endosomes to the trans -Golgi apparatus. Our data demonstrate that VPS52 and VPS54 were dispensable for mature virion (MV) production but were required for extracellular virus (EV) formation. For comparison, a known antiviral compound, ST-246, was used in our experiments, demonstrating that EV titers in VPS52 and VPS54 knockout (KO) cells were comparable to levels exhibited by ST-246-treated wild-type cells. Confocal microscopy was used to examine actin tail formation, one of the viral egress mechanisms for cell-to-cell dissemination, and revealed an absence of actin tails in VPS52KO- or VPS54KO-infected cells. Further evaluation of these cells by electron microscopy demonstrated a decrease in levels of wrapped viruses (WVs) compared to those seen with the wild-type control. Collectively, our data demonstrate the role of GARP complex genes in double-membrane wrapping of MVs necessary for EV formation, implicating the host endosomal trafficking pathway in orthopoxvirus infection. IMPORTANCE Human monkeypox is an emerging zoonotic infectious disease caused by Monkeypox virus (MPXV). Of the two MPXV clades, the Congo Basin strain is associated with severe

  20. Identifying the species origin of faecal droppings used for avian influenza virus surveillance in wild birds

    Science.gov (United States)

    Cheung, Peter P.; Leung, Y.H. Connie; Chow, Chun-Kin; Ng, Chi-Fung; Tsang, Chun-Lok; Wu, Yu-On; Ma, Siu-Kit; Sia, Sin-Fun; Guan, Yi; Peiris, J.S. Malik

    2009-01-01

    Background Avian influenza virus (AIV) surveillance in birds is important for public health. Faecal droppings from wild-birds are more readily available for such studies, but the inability to identify the species-origin of faecal samples limits their value. Objectives Develop, optimise, and field-test a method to simultaneously detect AIV and identify the species-origin from faecal samples. Study Design Analytical sensitivity of the species-identification RT-PCR was assessed on serial dilutions of faecal droppings. Overall sensitivity of the methods for species-identification and AIV detection was assessed on 92 faecal and cloacal samples collected from wildlife, poultry markets, and experimentally H5N1-infected birds. Results All 92 samples were correctly identified to 24 different species, with a detection limit of 2.8μg of faecal material. All 20 specimens previously shown by virus culture to be positive for influenza virus were correctly identified by RT-PCR for influenza A using the same nucleic acid extracts used for species-identification. Conclusions We have optimised and evaluated a method for identifying the species of origin and detecting AIV from bird faecal droppings that can be applied to routine surveillance of influenza viruses in wild-birds. PMID:19604718

  1. Phylogenetic Analysis of Rubella Viruses Identified in Uganda, 2003–2012

    Science.gov (United States)

    Namuwulya, Prossy; Abernathy, Emily; Bukenya, Henry; Bwogi, Josephine; Tushabe, Phionah; Birungi, Molly; Seguya, Ronald; Kabaliisa, Theopista; Alibu, Vincent P.; Kayondo, Jonathan K.; Rivailler, Pierre; Icenogle, Joseph; Bakamutumaho, Barnabas

    2014-01-01

    Molecular data on rubella viruses are limited in Uganda despite the importance of congenital rubella syndrome (CRS). Routine rubella vaccination, while not administered currently in Uganda, is expected to begin by 2015. The World Health Organization recommends that countries without rubella vaccination programs assess the burden of rubella and CRS before starting a routine vaccination program. Uganda is already involved in integrated case-based surveillance, including laboratory testing to confirm measles and rubella, but molecular epidemiologic aspects of rubella circulation have so far not been documented in Uganda. Twenty throat swab or oral fluid samples collected from 12 districts during routine rash and fever surveillance between 2003 and 2012 were identified as rubella virus RNA positive and PCR products encompassing the region used for genotyping were sequenced. Phylogenetic analysis of the 20 sequences identified 19 genotype 1G viruses and 1 genotype 1E virus. Genotype-specific trees showed that the Uganda viruses belonged to specific clusters for both genotypes 1G and 1E and grouped with similar sequences from neighboring countries. Genotype 1G was predominant in Uganda. More epidemiological and molecular epidemiological data are required to determine if genotype 1E is also endemic in Uganda. The information obtained in this study will assist the immunization program in monitoring changes in circulating genotypes. PMID:24700073

  2. DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY HEPATITIS E VIRUS IN WATER

    Science.gov (United States)

    Hepatitis E virus (HEV) causes an infectious form of hepatitis associated with contaminated water. By analyzing the sequence of several HEV isolates, a reverse transciption-polymerase chain reaction method was developed and optimized that should be able to identify all of the kn...

  3. Using InSAR time series to identify geologic hazards associated with the Hayward and Calaveras faults along the South Bay Aqueduct

    Science.gov (United States)

    Jones, C. E.; Burgmann, R.; Hoirup, D. F., Jr.; Hawkins, B.

    2016-12-01

    We evaluated Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) data using InSAR time series analysis and documented ground movement along the Calaveras and Hayward faults near the South Bay Aqueduct (SBA). Images from seven different UAVSAR flight lines at 7m x 7m resolution were used for the study. A total of 132 acquisitions (between 12 and 51 per line) were acquired between 2009 and 2015. Each of the seven lines observed only part of the aqueduct, but all segments of the aqueduct were imaged in more than one line with some segments in up to four lines. This provided between one and three imaging geometries for every fault location along the aqueduct. The SBA transports water from the Sacramento-San Joaquin Delta (Delta) to communities east and south of San Francisco Bay through a combination of open canals, tunnels, and pipelines. From its starting point immediately west of the Delta at Bethany Reservoir, the SBA extends westward, crossing multiple faults, including Calaveras and Hayward faults. The aqueduct continues south, largely following the Hayward fault to its terminus east of San Jose. The SBA and associated infrastructure are at risk from landslides and from movement along any of these faults, with the landslides often spatially associated with the faults. We report linear rates of surface movement averaged across the six-year time period, and identify locations experiencing significant movement along the Calaveras and Hayward faults. Aseismic displacement is quantified and mapped for the two faults, including multiple traces of the Calaveras fault extending north and south of where it crosses the SBA. This work was carried out in part at the Jet Propulsion Laboratory, California Institute of Technology, under contracts with the California Dept. of Water Resources and with the National Aeronautics and Space Administration.

  4. Cell culture and electron microscopy for identifying viruses in diseases of unknown cause.

    Science.gov (United States)

    Goldsmith, Cynthia S; Ksiazek, Thomas G; Rollin, Pierre E; Comer, James A; Nicholson, William L; Peret, Teresa C T; Erdman, Dean D; Bellini, William J; Harcourt, Brian H; Rota, Paul A; Bhatnagar, Julu; Bowen, Michael D; Erickson, Bobbie R; McMullan, Laura K; Nichol, Stuart T; Shieh, Wun-Ju; Paddock, Christopher D; Zaki, Sherif R

    2013-06-01

    During outbreaks of infectious diseases or in cases of severely ill patients, it is imperative to identify the causative agent. This report describes several events in which virus isolation and identification by electron microscopy were critical to initial recognition of the etiologic agent, which was further analyzed by additional laboratory diagnostic assays. Examples include severe acute respiratory syndrome coronavirus, and Nipah, lymphocytic choriomeningitis, West Nile, Cache Valley, and Heartland viruses. These cases illustrate the importance of the techniques of cell culture and electron microscopy in pathogen identification and recognition of emerging diseases.

  5. Hepatitis E virus incidence in patients with non-identified acute viral hepatitis in Mexico

    OpenAIRE

    Berebichez-Fridman, R.; Vázquez-Campuzano, R.; Galnares-Olalde, J.A.; Blachman-Braun, R.

    2016-01-01

    Introduction: Hepatitis E virus (HEV) is one of the identified pathogens that cause acute viral hepatitis in Mexico. It has been observed that the presence of this particular pathogen represents a great risk in pregnant women and solid organ transplant recipients. In Mexico there are no formal epidemiological reports about HEV. The objective of this study is to determine the incidence of HEV infection in Mexican patients with non-identified viral infection, and to provide a general perspectiv...

  6. The potential of targeted antibody prophylaxis in SARS outbreak control: a mathematic analysis

    NARCIS (Netherlands)

    Bogaards, Johannes Antonie; Putter, Hein; Jan Weverling, Gerrit; ter Meulen, Jan; Goudsmit, Jaap

    2007-01-01

    BACKGROUND: Severe acute respiratory syndrome (SARS) coronavirus-like viruses continue to circulate in animal reservoirs. If new mutants of SARS coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that

  7. Learning from Experience: The Public Health Response to West Nile Virus, SARS, Monkeypox, and Hepatitis A Outbreaks in the United States

    Science.gov (United States)

    2005-01-01

    mosquito densities and infection rates over time and space Human • Focus on encephalitis • Aseptic meningitis, Guillain - Barre syndrome , acute flaccid...local health departments to recent disease outbreaks—specifically, Severe Acute Respiratory Syndrome (SARS), monkeypox, and West Nile virus—to address...149 Appendix C: Severe Acute Respiratory Syndrome (SARS

  8. Calibration of channel depth and friction parameters in the LISFLOOD-FP hydraulic model using medium resolution SAR data and identifiability techniques

    NARCIS (Netherlands)

    Wood, Melissa; hostache, renaud; Neal, J. C.; wagener, thorsten; giustarini, laura; chini, marco; corato, giovani; matgen, patrick; Bates, P. D.

    2016-01-01

    Single satellite synthetic aperture radar (SAR) data are now regularly used to estimate hydraulic model parameters such as channel roughness, depth and water slope. However, despite channel geometry being critical to the application of hydraulic models and poorly known a priori, it is not frequently

  9. A BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus.

    Science.gov (United States)

    Tigabu, Bersabeh; Rasmussen, Lynn; White, E Lucile; Tower, Nichole; Saeed, Mohammad; Bukreyev, Alexander; Rockx, Barry; LeDuc, James W; Noah, James W

    2014-04-01

    Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect. From this pilot effort, 23 compounds were identified with EC50 values ranging from 3.9 to 20.0 μM and selectivities >10. Three sulfonamide compounds with EC50 values <12 μM were further characterized for their point of intervention in the viral replication cycle and for broad antiviral efficacy. Development of HTS capability under BSL-4 containment changes the paradigm for drug discovery for highly pathogenic agents because this platform can be readily modified to identify prophylactic and postexposure therapeutic candidates against other BSL-4 pathogens, particularly Ebola, Marburg, and Lassa viruses.

  10. Identifying gp85-regions involved in Epstein-Barr virus binding to B-lymphocytes.

    Science.gov (United States)

    Urquiza, Mauricio; Suarez, Jorge; Lopez, Ramses; Vega, Erika; Patino, Helena; Garcia, Javier; Patarroyo, Manuel A; Guzman, Fanny; Patarroyo, Manuel E

    2004-06-18

    Epstein-Barr virus lacking glycoprotein gp85 cannot infect B-cells and epithelial cells. The gp85 belongs to the molecular complex required for virus invasion of B-lymphocyte or epithelial cells. Moreover, there is evidence that gp85 is necessary for virus attachment to epithelial cells. Thirty-six peptides from the entire gp85-sequence were tested in epithelial and lymphoblastoid cell line binding assays to identify gp85-regions involved in virus-cell interaction. Five of these peptides presented high binding activity to Raji, Ramos, P3HR-1, and HeLa cells, but not to erythrocytes; Raji-cell affinity constants were between 80 and 140nM. Of these five peptides, 11435 ((181)TYKRVTEKGDEHVLSLVFGK(200)), 11436 ((201)TKDLPDLRGPFSYPSLTSAQ(220)), and 11438 ((241)YFVPNLKDMFSRAVTMTAAS(260)) bound to a 65kDa protein on Raji-cell surface. These peptides and antibodies induced by them (recognising live EBV-infected cells) inhibited Epstein-Barr virus interaction with cord blood lymphocytes. It is thus probable that gp85-regions defined by peptides 11435, 11436, and 11438 are involved in EBV invasion of B-lymphocytes.

  11. Data fusion and machine learning to identify threat vectors for the Zika virus and classify vulnerability

    Science.gov (United States)

    Gentle, J. N., Jr.; Kahn, A.; Pierce, S. A.; Wang, S.; Wade, C.; Moran, S.

    2016-12-01

    With the continued spread of the zika virus in the United States in both Florida and Virginia, increased public awareness, prevention and targeted prediction is necessary to effectively mitigate further infection and propagation of the virus throughout the human population. The goal of this project is to utilize publicly accessible data and HPC resources coupled with machine learning algorithms to identify potential threat vectors for the spread of the zika virus in Texas, the United States and globally by correlating available zika case data collected from incident reports in medical databases (e.g., CDC, Florida Department of Health) with known bodies of water in various earth science databases (e.g., USGS NAQWA Data, NASA ASTER Data, TWDB Data) and by using known mosquito population centers as a proxy for trends in population distribution (e.g., WHO, European CDC, Texas Data) while correlating historical trends in the spread of other mosquito borne diseases (e.g., chikungunya, malaria, dengue, yellow fever, west nile, etc.). The resulting analysis should refine the identification of the specific threat vectors for the spread of the virus which will correspondingly increase the effectiveness of the limited resources allocated towards combating the disease through better strategic implementation of defense measures. The minimal outcome of this research is a better understanding of the factors involved in the spread of the zika virus, with the greater potential to save additional lives through more effective resource utilization and public outreach.

  12. Novel Ranking System for Identifying Efficacious Anti-Influenza Virus PB2 Inhibitors.

    Science.gov (United States)

    Tsai, Alice W; McNeil, Colleen F; Leeman, Joshua R; Bennett, Hamilton B; Nti-Addae, Kwame; Huang, Cassey; Germann, Ursula A; Byrn, Randal A; Berlioz-Seux, Francoise; Rijnbrand, Rene; Clark, Michael P; Charifson, Paul S; Jones, Steven M

    2015-10-01

    Through antigenic drift and shifts, influenza virus infections continue to be an annual cause of morbidity in healthy populations and of death among elderly and at-risk patients. The emergence of highly pathogenic avian influenza viruses such as H5N1 and H7N9 and the rapid spread of the swine-origin H1N1 influenza virus in 2009 demonstrate the continued need for effective therapeutic agents for influenza. While several neuraminidase inhibitors have been developed for the treatment of influenza virus infections, these have shown a limited window for treatment initiation, and resistant variants have been noted in the population. In addition, an older class of antiviral drugs for influenza, the adamantanes, are no longer recommended for treatment due to widespread resistance. There remains a need for new influenza therapeutic agents with improved efficacy as well as an expanded window for the initiation of treatment. Azaindole compounds targeting the influenza A virus PB2 protein and demonstrating excellent in vitro and in vivo properties have been identified. To evaluate the in vivo efficacy of these PB2 inhibitors, we utilized a mouse influenza A virus infection model. In addition to traditional endpoints, i.e., death, morbidity, and body weight loss, we measured lung function using whole-body plethysmography, and we used these data to develop a composite efficacy score that takes compound exposure into account. This model allowed the rapid identification and ranking of molecules relative to each other and to oseltamivir. The ability to identify compounds with enhanced preclinical properties provides an opportunity to develop more-effective treatments for influenza in patients. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus.

    Science.gov (United States)

    Josset, Laurence; Menachery, Vineet D; Gralinski, Lisa E; Agnihothram, Sudhakar; Sova, Pavel; Carter, Victoria S; Yount, Boyd L; Graham, Rachel L; Baric, Ralph S; Katze, Michael G

    2013-04-30

    A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus. Identification of a novel coronavirus causing fatal respiratory infection in humans raises concerns about a possible widespread outbreak of severe respiratory infection similar to the one caused by SARS-CoV. Using a human lung epithelial cell line and global transcriptomic profiling, we identified differences in the host response between HCoV-EMC and SARS-CoV. This enables rapid assessment of viral properties and the

  14. The effect of inhibition of PP1 and TNFα signaling on pathogenesis of SARS coronavirus.

    Science.gov (United States)

    McDermott, Jason E; Mitchell, Hugh D; Gralinski, Lisa E; Eisfeld, Amie J; Josset, Laurence; Bankhead, Armand; Neumann, Gabriele; Tilton, Susan C; Schäfer, Alexandra; Li, Chengjun; Fan, Shufang; McWeeney, Shannon; Baric, Ralph S; Katze, Michael G; Waters, Katrina M

    2016-09-23

    The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation.

  15. Genome-wide analysis of Epstein-Barr virus identifies variants and genes associated with gastric carcinoma and population structure.

    Science.gov (United States)

    Yao, Youyuan; Xu, Miao; Liang, Liming; Zhang, Haojiong; Xu, Ruihua; Feng, Qisheng; Feng, Lin; Luo, Bing; Zeng, Yi-Xin

    2017-10-01

    Epstein-Barr virus is a ubiquitous virus and is associated with several human malignances, including the significant subset of gastric carcinoma, Epstein-Barr virus-associated gastric carcinoma. Some Epstein-Barr virus-associated diseases are uniquely prevalent in populations with different geographic origins. However, the features of the disease and geographically associated Epstein-Barr virus genetic variation as well as the roles that the variation plays in carcinogenesis and evolution remain unclear. Therefore, in this study, we sequenced 95 geographically distinct Epstein-Barr virus isolates from Epstein-Barr virus-associated gastric carcinoma biopsies and saliva of healthy donors to detect variants and genes associated with gastric carcinoma and population structure from a genome-wide spectrum. We demonstrated that Epstein-Barr virus revealed the population structure between North China and South China. In addition, we observed population stratification between Epstein-Barr virus strains from gastric carcinoma and healthy controls, indicating that certain Epstein-Barr virus subtypes are associated with different gastric carcinoma risks. We identified that the BRLF1, BBRF3, and BBLF2/BBLF3 genes had significant associations with gastric carcinoma. LMP1 and BNLF2a genes were strongly geographically associated genes in Epstein-Barr virus. Our study provides insights into the genetic basis of oncogenic Epstein-Barr virus for gastric carcinoma, and the genetic variants associated with gastric carcinoma can serve as biomarkers for oncogenic Epstein-Barr virus.

  16. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants.

    Directory of Open Access Journals (Sweden)

    Damon Deming

    2006-12-01

    Full Text Available In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge.Using Venezuelan equine encephalitis virus replicon particles (VRP expressing the 2003 epidemic Urbani SARS-CoV strain spike (S glycoprotein (VRP-S or the nucleocapsid (N protein from the same strain (VRP-N, we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic

  17. Development of a single nucleotide polymorphism DNA microarray for the detection and genotyping of the SARS coronavirus.

    Science.gov (United States)

    Guo, Xi; Geng, Peng; Wang, Quan; Cao, Boyang; Liu, Bin

    2014-10-01

    Severe acute respiratory syndrome (SARS), a disease that spread widely in the world during late 2002 to 2004, severely threatened public health. Although there have been no reported infections since 2004, the extremely pathogenic SARS coronavirus (SARS-CoV), as the causative agent of SARS, has recently been identified in animals, showing the potential for the re-emergence of this disease. Previous studies showed that 27 single nucleotide polymorphism (SNP) mutations among the spike (S) gene of this virus are correlated closely with the SARS pathogenicity and epidemicity. We have developed a SNP DNA microarray in order to detect and genotype these SNPs, and to obtain related information on the pathogenicity and epidemicity of a given strain. The microarray was hybridized with PCR products amplified from cDNAs obtained from different SARS-CoV strains. We were able to detect 24 SNPs and determine the type of a given strain. The hybridization profile showed that 19 samples were detected and genotyped correctly by using our microarray, with 100% accuracy. Our microarray provides a novel method for the detection and epidemiological surveillance of SARS-CoV.

  18. Yeast based small molecule screen for inhibitors of SARS-CoV.

    Directory of Open Access Journals (Sweden)

    Matthew Frieman

    Full Text Available Severe acute respiratory coronavirus (SARS-CoV emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells.

  19. Geodetic SAR Tomography

    NARCIS (Netherlands)

    Zhu, Xiao Xiang; Montazeri, Sina; Gisinger, Christoph; Hanssen, R.F.; Bamler, Richard

    2016-01-01

    In this paper, we propose a framework referred to as 'geodetic synthetic aperture radar (SAR) tomography' that fuses the SAR imaging geodesy and tomographic SAR inversion (TomoSAR) approaches to obtain absolute 3-D positions of a large amount of natural scatterers. The methodology is applied on

  20. The Ebola virus VP35 protein binds viral immunostimulatory and host RNAs identified through deep sequencing.

    Directory of Open Access Journals (Sweden)

    Kari A Dilley

    Full Text Available Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV, and this IFN-antagonist activity is directly correlated with its ability to bind RNA. Several structural studies demonstrate that VP35 binds short synthetic dsRNAs; yet, there are no data that identify viral immunostimulatory RNAs (isRNA or host RNAs bound to VP35 in cells. Utilizing a SeV infection model, we demonstrate that both viral isRNA and host RNAs are bound to Ebola and Marburg VP35s in cells. By deep sequencing the purified VP35-bound RNA, we identified the SeV copy-back defective interfering (DI RNA, previously identified as a robust RIG-I activator, as the isRNA bound by multiple filovirus VP35 proteins, including the VP35 protein from the West African outbreak strain (Makona EBOV. Moreover, RNAs isolated from a VP35 RNA-binding mutant were not immunostimulatory and did not include the SeV DI RNA. Strikingly, an analysis of host RNAs bound by wild-type, but not mutant, VP35 revealed that select host RNAs are preferentially bound by VP35 in cell culture. Taken together, these data support a model in which VP35 sequesters isRNA in virus-infected cells to avert RIG-I like receptor (RLR activation.

  1. Analysis of summer subsidence in Barrow, Alaska, using InSAR and hyperspectral remote sensing

    OpenAIRE

    Mahmud Haghshenas Haghighi; M. Motagh; B. Heim; S. Chabrillat; D. Streletskiy; G. Grosse; T. Sachs; Katrin Kohnert

    2016-01-01

    In this study, gradual elevation change due to summer thawing of active layer in tundra permafrost landscape of Barrow, Alaska is investigated using SAR interferometry (InSAR) technique. We used a variety of SAR sensors including TerraSAR-X, ALOS, and Sentinel-1 images to assess elevation changes in summer season. Preliminary result, obtained by TerraSAR-X InSAR analysis, clearly delineates subsidence during the summer by identifying thousands of coherent pixels on ...

  2. Proteomic Analysis of Pichindé virus Infection Identifies Differential Expression of Prothymosin-α

    Directory of Open Access Journals (Sweden)

    Gavin C. Bowick

    2010-01-01

    Full Text Available The arenaviruses include a number of important pathogens including Lassa virus and Junin virus. Presently, the only treatment is supportive care and the antiviral Ribavirin. In the event of an epidemic, patient triage may be required to more effectively manage resources; the development of prognostic biomarker signatures, correlating with disease severity, would allow rational triage. Using a pair of arenaviruses, which cause mild or severe disease, we analyzed extracts from infected cells using SELDI mass spectrometry to characterize potential biomarker profiles. EDGE analysis was used to analyze longitudinal expression differences. Extracts from infected guinea pigs revealed protein peaks which could discriminate between mild or severe infection and between times post-infection. Tandem mass-spectrometry identified several peaks, including the transcriptional regulator prothymosin-α. Further investigation revealed differences in secretion of this peptide. These data show proof of concept that proteomic profiling of host markers could be used as prognostic markers of infectious disease.

  3. VirusSeq: software to identify viruses and their integration sites using next-generation sequencing of human cancer tissue.

    Science.gov (United States)

    Chen, Yunxin; Yao, Hui; Thompson, Erika J; Tannir, Nizar M; Weinstein, John N; Su, Xiaoping

    2013-01-15

    We developed a new algorithmic method, VirusSeq, for detecting known viruses and their integration sites in the human genome using next-generation sequencing data. We evaluated VirusSeq on whole-transcriptome sequencing (RNA-Seq) data of 256 human cancer samples from The Cancer Genome Atlas. Using these data, we showed that VirusSeq accurately detects the known viruses and their integration sites with high sensitivity and specificity. VirusSeq can also perform this function using whole-genome sequencing data of human tissue. VirusSeq has been implemented in PERL and is available at http://odin.mdacc.tmc.edu/∼xsu1/VirusSeq.html. xsu1@mdanderson.org Supplementary data are available at Bioinformatics online.

  4. Improving the selection and development of influenza vaccine viruses - Report of a WHO informal consultation on improving influenza vaccine virus selection, Hong Kong SAR, China, 18-20 November 2015.

    Science.gov (United States)

    Hampson, Alan; Barr, Ian; Cox, Nancy; Donis, Ruben O; Siddhivinayak, Hirve; Jernigan, Daniel; Katz, Jacqueline; McCauley, John; Motta, Fernando; Odagiri, Takato; Tam, John S; Waddell, Anthony; Webby, Richard; Ziegler, Thedi; Zhang, Wenqing

    2017-02-22

    Since 2010 the WHO has held a series of informal consultations to explore ways of improving the currently highly complex and time-pressured influenza vaccine virus selection and development process. In November 2015 experts from around the world met to review the current status of efforts in this field. Discussion topics included strengthening influenza surveillance activities to increase the availability of candidate vaccine viruses and improve the extent, timeliness and quality of surveillance data. Consideration was also given to the development and potential application of newer laboratory assays to better characterize candidate vaccine viruses, the potential importance of antibodies directed against influenza virus neuraminidase, and the role of vaccine effectiveness studies. Advances in next generation sequencing and whole genome sequencing of influenza viruses were also discussed, along with associated developments in synthetic genomics technologies, evolutionary analysis and predictive mathematical modelling. Discussions were also held on the late emergence of an antigenic variant influenza A(H3N2) virus in mid-2014 that could not be incorporated in time into the 2014-15 northern hemisphere vaccine. There was broad recognition that given the current highly constrained influenza vaccine development and production timeline it would remain impossible to incorporate any variant virus which emerged significantly long after the relevant WHO biannual influenza vaccine composition meetings. Discussions were also held on the development of pandemic and broadly protective vaccines, and on associated regulatory and manufacturing requirements and constraints. With increasing awareness of the health and economic burdens caused by seasonal influenza, the ever-present threat posed by zoonotic influenza viruses, and the significant impact of the 2014-15 northern hemisphere seasonal influenza vaccine mismatch, this consultation provided a very timely opportunity to share

  5. Complete genome sequence of a novel extrachromosomal virus-like element identified in planarian Girardia tigrina

    Directory of Open Access Journals (Sweden)

    Vagner Loura L

    2002-06-01

    Full Text Available Abstract Background Freshwater planarians are widely used as models for investigation of pattern formation and studies on genetic variation in populations. Despite extensive information on the biology and genetics of planaria, the occurrence and distribution of viruses in these animals remains an unexplored area of research. Results Using a combination of Suppression Subtractive Hybridization (SSH and Mirror Orientation Selection (MOS, we compared the genomes of two strains of freshwater planarian, Girardia tigrina. The novel extrachromosomal DNA-containing virus-like element denoted PEVE (Planarian Extrachromosomal Virus-like Element was identified in one planarian strain. The PEVE genome (about 7.5 kb consists of two unique regions (Ul and Us flanked by inverted repeats. Sequence analyses reveal that PEVE comprises two helicase-like sequences in the genome, of which the first is a homolog of a circoviral replication initiator protein (Rep, and the second is similar to the papillomavirus E1 helicase domain. PEVE genome exists in at least two variant forms with different arrangements of single-stranded and double-stranded DNA stretches that correspond to the Us and Ul regions. Using PCR analysis and whole-mount in situ hybridization, we characterized PEVE distribution and expression in the planarian body. Conclusions PEVE is the first viral element identified in free-living flatworms. This element differs from all known viruses and viral elements, and comprises two potential helicases that are homologous to proteins from distant viral phyla. PEVE is unevenly distributed in the worm body, and is detected in specific parenchyma cells.

  6. A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection.

    Science.gov (United States)

    Riblett, Amber M; Blomen, Vincent A; Jae, Lucas T; Altamura, Louis A; Doms, Robert W; Brummelkamp, Thijn R; Wojcechowskyj, Jason A

    2015-11-18

    Rift Valley fever virus (RVFV) causes recurrent insect-borne epizootics throughout the African continent, and infection of humans can lead to a lethal hemorrhagic fever syndrome. Deep mutagenesis of haploid human cells was used to identify host factors required for RVFV infection. This screen identified a suite of enzymes involved in glycosaminoglycan (GAG) biogenesis and transport, including several components of the cis-oligomeric Golgi (COG) complex, one of the central components of Golgi complex trafficking. In addition, disruption of PTAR1 led to RVFV resistance as well as reduced heparan sulfate surface levels, consistent with recent observations that PTAR1-deficient cells exhibit altered Golgi complex morphology and glycosylation defects. A variety of biochemical and genetic approaches were utilized to show that both pathogenic and attenuated RVFV strains require GAGs for efficient infection on some, but not all, cell types, with the block to infection being at the level of virion attachment. Examination of other members of the Bunyaviridae family for GAG-dependent infection suggested that the interaction with GAGs is not universal among bunyaviruses, indicating that these viruses, as well as RVFV on certain cell types, employ additional unidentified virion attachment factors and/or receptors. Rift Valley fever virus (RVFV) is an emerging pathogen that can cause severe disease in humans and animals. Epizootics among livestock populations lead to high mortality rates and can be economically devastating. Human epidemics of Rift Valley fever, often initiated by contact with infected animals, are characterized by a febrile disease that sometimes leads to encephalitis or hemorrhagic fever. The global burden of the pathogen is increasing because it has recently disseminated beyond Africa, which is of particular concern because the virus can be transmitted by widely distributed mosquito species. There are no FDA-licensed vaccines or antiviral agents with activity

  7. Identifying potential virulence determinants in viral haemorrhagic septicaemia virus (VHSV) for rainbow trout

    DEFF Research Database (Denmark)

    Campbell, Scott; Collet, Bertrand; Einer-Jensen, Katja

    2009-01-01

    We identified viral haemorrhagic septicaemia virus (VHSV) isolates classified within Genotype Ib which are genetically similar (>99.4% glycoprotein amino acid identity) yet, based on their isolation history, were suspected to differ in virulence in juvenile rainbow trout. The virulence...... of an isolate recovered in 2000 from a viral haemorrhagic septicaemia disease episode in a marine rainbow trout farm in Sweden (SE-SVA-1033) was evaluated in juvenile rainbow trout via intraperitoneal injection and immersion challenge alongside 3 isolates recovered from wild-caught marine fish (DK-4p37, DK-5e59...

  8. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor.

    Science.gov (United States)

    Ge, Xing-Yi; Li, Jia-Lu; Yang, Xing-Lou; Chmura, Aleksei A; Zhu, Guangjian; Epstein, Jonathan H; Mazet, Jonna K; Hu, Ben; Zhang, Wei; Peng, Cheng; Zhang, Yu-Ji; Luo, Chu-Ming; Tan, Bing; Wang, Ning; Zhu, Yan; Crameri, Gary; Zhang, Shu-Yi; Wang, Lin-Fa; Daszak, Peter; Shi, Zheng-Li

    2013-11-28

    The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.

  9. Chemical Genomics Identifies the PERK-Mediated Unfolded Protein Stress Response as a Cellular Target for Influenza Virus Inhibition

    Directory of Open Access Journals (Sweden)

    Sara Landeras-Bueno

    2016-04-01

    Full Text Available Influenza A viruses generate annual epidemics and occasional pandemics of respiratory disease with important consequences for human health and the economy. Therefore, a large effort has been devoted to the development of new anti-influenza virus drugs directed to viral targets, as well as to the identification of cellular targets amenable to anti-influenza virus therapy. Here we have addressed the identification of such potential cellular targets by screening collections of drugs approved for human use. We reasoned that screening with a green fluorescent protein-based recombinant replicon system would identify cellular targets involved in virus transcription/replication and/or gene expression and hence address an early stage of virus infection. By using such a strategy, we identified Montelukast (MK as an inhibitor of virus multiplication. MK inhibited virus gene expression but did not alter viral RNA synthesis in vitro or viral RNA accumulation in vivo. The low selectivity index of MK prevented its use as an antiviral, but it was sufficient to identify a new cellular pathway suitable for anti-influenza virus intervention. By deep sequencing of RNA isolated from mock- and virus-infected human cells, treated with MK or left untreated, we showed that it stimulates the PERK-mediated unfolded protein stress response. The phosphorylation of PERK was partly inhibited in virus-infected cells but stimulated in MK-treated cells. Accordingly, pharmacological inhibition of PERK phosphorylation led to increased viral gene expression, while inhibition of PERK phosphatase reduced viral protein synthesis. These results suggest the PERK-mediated unfolded protein response as a potential cellular target to modulate influenza virus infection.

  10. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

    NARCIS (Netherlands)

    Hamming, [No Value; Timens, W; Bulthuis, MLC; Lely, AT; Navis, GJ; van Goor, H

    Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) has been

  11. FluShuffle and FluResort: new algorithms to identify reassorted strains of the influenza virus by mass spectrometry

    National Research Council Canada - National Science Library

    Lun, Aaron Tl; Wong, Jason Wh; Downard, Kevin M

    2012-01-01

    ... pandemic, resulting in tens of millions of deaths. We have developed and tested new computer algorithms, FluShuffle and FluResort, which enable reassorted viruses to be identified by the most rapid and direct means possible...

  12. Metagenomic characterization of the virome associated with bovine respiratory disease in feedlot cattle identified novel viruses and suggests an etiologic role for influenza D virus.

    Science.gov (United States)

    Mitra, Namita; Cernicchiaro, Natalia; Torres, Siddartha; Li, Feng; Hause, Ben M

    2016-08-01

    Bovine respiratory disease (BRD) is the most costly disease affecting the cattle industry. The pathogenesis of BRD is complex and includes contributions from microbial pathogens as well as host, environmental and animal management factors. In this study, we utilized viral metagenomic sequencing to explore the virome of nasal swab samples obtained from feedlot cattle with acute BRD and asymptomatic pen-mates at six and four feedlots in Mexico and the USA, respectively, in April-October 2015. Twenty-one viruses were detected, with bovine rhinitis A (52.7 %) and B (23.7 %) virus, and bovine coronavirus (24.7 %) being the most commonly identified. The emerging influenza D virus (IDV) tended to be significantly associated (P=0.134; odds ratio=2.94) with disease, whereas viruses commonly associated with BRD such as bovine viral diarrhea virus, bovine herpesvirus 1, bovine respiratory syncytial virus and bovine parainfluenza 3 virus were detected less frequently. The detection of IDV was further confirmed using a real-time PCR assay. Nasal swabs from symptomatic animals had significantly more IDV RNA than those collected from healthy animals (P=0.04). In addition to known viruses, new genotypes of bovine rhinitis B virus and enterovirus E were identified and a newly proposed species of bocaparvovirus, Ungulate bocaparvovirus 6, was characterized. Ungulate tetraparvovirus 1 was also detected for the first time in North America to our knowledge. These results illustrate the complexity of the virome associated with BRD and highlight the need for further research into the contribution of other viruses to BRD pathogenesis.

  13. Multiple oncogenic viruses identified in Ocular surface squamous neoplasia in HIV-1 patients

    Directory of Open Access Journals (Sweden)

    Bisson Gregory

    2010-03-01

    Full Text Available Abstract Background Ocular surface squamous neoplasia (OSSN is a rare cancer that has increased in incidence with the HIV pandemic in Africa. The underlying cause of this cancer in HIV-infected patients from Botswana is not well defined. Results Tissues were obtained from 28 OSSN and 8 pterygia patients. The tissues analyzed from OSSN patients were 83% positive for EBV, 75% were HPV positive, 70% were KSHV positive, 75% were HSV-1/2 positive, and 61% were CMV positive by PCR. Tissues from pterygium patients were 88% positive for EBV, 75% were HPV positive, 50% were KSHV positive, and 60% were CMV positive. None of the patients were JC or BK positive. In situ hybridization and immunohistochemistry analyses further identified HPV, EBV, and KSHV in a subset of the tissue samples. Conclusion We identified the known oncogenic viruses HPV, KSHV, and EBV in OSSN and pterygia tissues. The presence of these tumor viruses in OSSN suggests that they may contribute to the development of this malignancy in the HIV population. Further studies are necessary to characterize the molecular mechanisms associated with viral antigens and their potential role in the development of OSSN.

  14. Identifying recombinants in human and primate immunodeficiency virus sequence alignments using quartet scanning

    Directory of Open Access Journals (Sweden)

    Martin Darren P

    2009-04-01

    Full Text Available Abstract Background Recombination has a profound impact on the evolution of viruses, but characterizing recombination patterns in molecular sequences remains a challenging endeavor. Despite its importance in molecular evolutionary studies, identifying the sequences that exhibit such patterns has received comparatively less attention in the recombination detection framework. Here, we extend a quartet-mapping based recombination detection method to enable identification of recombinant sequences without prior specifications of either query and reference sequences. Through simulations we evaluate different recombinant identification statistics and significance tests. We compare the quartet approach with triplet-based methods that employ additional heuristic tests to identify parental and recombinant sequences. Results Analysis of phylogenetic simulations reveal that identifying the descendents of relatively old recombination events is a challenging task for all methods available, and that quartet scanning performs relatively well compared to the triplet based methods. The use of quartet scanning is further demonstrated by analyzing both well-established and putative HIV-1 recombinant strains. In agreement with recent findings, we provide evidence that the presumed circulating recombinant CRF02_AG is a 'pure' lineage, whereas the presumed parental lineage subtype G has a recombinant origin. We also demonstrate HIV-1 intrasubtype recombination, confirm the hybrid origin of SIV in chimpanzees and further disentangle the recombinant history of SIV lineages in a primate immunodeficiency virus data set. Conclusion Quartet scanning makes a valuable addition to triplet-based methods for identifying recombinant sequences without prior specifications of either query and reference sequences. The new method is available in the VisRD v.3.0 package http://www.cmp.uea.ac.uk/~vlm/visrd.

  15. Identification of residues of SARS-CoV nsp1 that differentially affect inhibition of gene expression and antiviral signaling.

    Science.gov (United States)

    Jauregui, Andrew R; Savalia, Dhruti; Lowry, Virginia K; Farrell, Cara M; Wathelet, Marc G

    2013-01-01

    An epidemic of Severe Acute Respiratory Syndrome (SARS) led to the identification of an associated coronavirus, SARS-CoV. This virus evades the host innate immune response in part through the expression of its non-structural protein (nsp) 1, which inhibits both host gene expression and virus- and interferon (IFN)-dependent signaling. Thus, nsp1 is a promising target for drugs, as inhibition of nsp1 would make SARS-CoV more susceptible to the host antiviral defenses. To gain a better understanding of nsp1 mode of action, we generated and analyzed 38 mutants of the SARS-CoV nsp1, targeting 62 solvent exposed residues out of the 180 amino acid protein. From this work, we identified six classes of mutants that abolished, attenuated or increased nsp1 inhibition of host gene expression and/or antiviral signaling. Each class of mutants clustered on SARS-CoV nsp1 surface and suggested nsp1 interacts with distinct host factors to exert its inhibitory activities. Identification of the nsp1 residues critical for its activities and the pathways involved in these activities should help in the design of drugs targeting nsp1. Significantly, several point mutants increased the inhibitory activity of nsp1, suggesting that coronaviruses could evolve a greater ability to evade the host response through mutations of such residues.

  16. Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and genetic variation analysis.

    Science.gov (United States)

    Ren, Wuze; Li, Wendong; Yu, Meng; Hao, Pei; Zhang, Yuan; Zhou, Peng; Zhang, Shuyi; Zhao, Guoping; Zhong, Yang; Wang, Shengyue; Wang, Lin-Fa; Shi, Zhengli

    2006-11-01

    Bats were recently identified as natural reservoirs of SARS-like coronavirus (SL-CoV) or SARS coronavirus-like virus. These viruses, together with SARS coronaviruses (SARS-CoV) isolated from human and palm civet, form a distinctive cluster within the group 2 coronaviruses of the genus Coronavirus, tentatively named group 2b (G2b). In this study, complete genome sequences of two additional group 2b coronaviruses (G2b-CoVs) were determined from horseshoe bat Rhinolophus ferrumequinum (G2b-CoV Rf1) and Rhinolophus macrotis (G2b-CoV Rm1). The bat G2b-CoV isolates have an identical genome organization and share an overall genome sequence identity of 88-92 % among themselves and between them and the human/civet isolates. The most variable regions are located in the genes encoding nsp3, ORF3a, spike protein and ORF8 when bat and human/civet G2b-CoV isolates are compared. Genetic analysis demonstrated that a diverse G2b-CoV population exists in the bat habitat and has evolved from a common ancestor of SARS-CoV.

  17. GeneChip Resequencing of the Smallpox Virus Genome Can Identify Novel Strains: a Biodefense Application▿

    Science.gov (United States)

    Sulaiman, Irshad M.; Tang, Kevin; Osborne, John; Sammons, Scott; Wohlhueter, Robert M.

    2007-01-01

    We developed a set of seven resequencing GeneChips, based on the complete genome sequences of 24 strains of smallpox virus (variola virus), for rapid characterization of this human-pathogenic virus. Each GeneChip was designed to analyze a divergent segment of approximately 30,000 bases of the smallpox virus genome. This study includes the hybridization results of 14 smallpox virus strains. Of the 14 smallpox virus strains hybridized, only 7 had sequence information included in the design of the smallpox virus resequencing GeneChips; similar information for the remaining strains was not tiled as a reference in these GeneChips. By use of variola virus-specific primers and long-range PCR, 22 overlapping amplicons were amplified to cover nearly the complete genome and hybridized with the smallpox virus resequencing GeneChip set. These GeneChips were successful in generating nucleotide sequences for all 14 of the smallpox virus strains hybridized. Analysis of the data indicated that the GeneChip resequencing by hybridization was fast and reproducible and that the smallpox virus resequencing GeneChips could differentiate the 14 smallpox virus strains characterized. This study also suggests that high-density resequencing GeneChips have potential biodefense applications and may be used as an alternate tool for rapid identification of smallpox virus in the future. PMID:17182757

  18. A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death.

    Science.gov (United States)

    Ma, Hongming; Dang, Ying; Wu, Yonggan; Jia, Gengxiang; Anaya, Edgar; Zhang, Junli; Abraham, Sojan; Choi, Jang-Gi; Shi, Guojun; Qi, Ling; Manjunath, N; Wu, Haoquan

    2015-07-28

    West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virus-induced cell death is poorly understood. Using a library containing 77,406 sgRNAs targeting 20,121 genes, we performed a genome-wide screen followed by a second screen with a sub-library. Among the genes identified, seven genes, EMC2, EMC3, SEL1L, DERL2, UBE2G2, UBE2J1, and HRD1, stood out as having the strongest phenotype, whose knockout conferred strong protection against WNV-induced cell death with two different WNV strains and in three cell lines. Interestingly, knockout of these genes did not block WNV replication. Thus, these appear to be essential genes that link WNV replication to downstream cell death pathway(s). In addition, the fact that all of these genes belong to the ER-associated protein degradation (ERAD) pathway suggests that this might be the primary driver of WNV-induced cell death. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. High Content Image Based Analysis Identifies Cell Cycle Inhibitors as Regulators of Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    Sina Bavari

    2012-09-01

    Full Text Available Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.

  20. Unraveling the complexities of the interferon response during SARS-CoV infection

    OpenAIRE

    Lang, Anna; Baas, Tracey; Smits, Saskia L.; Katze, Michael G.; Osterhaus, Albert DME; Haagmans, Bart L.

    2009-01-01

    Viruses employ different strategies to circumvent the antiviral actions of the innate immune response. SARS coronavirus (SARS-CoV), a virus that causes severe lung damage, encodes an array of proteins able to inhibit induction and signaling of type-I interferons. However, recent studies have demonstrated that interferons are produced during SARS-CoV infection in humans and macaques. Furthermore, nuclear translocation of activated STAT1 and a range of interferon-stimulated genes could be demon...

  1. Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice.

    Science.gov (United States)

    Gralinski, Lisa E; Menachery, Vineet D; Morgan, Andrew P; Totura, Allison L; Beall, Anne; Kocher, Jacob; Plante, Jessica; Harrison-Shostak, D Corinne; Schäfer, Alexandra; Pardo-Manuel de Villena, Fernando; Ferris, Martin T; Baric, Ralph S

    2017-06-07

    Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc. We generated 264 F2 mice between these strains, and infected them with SARS-CoV. Weight loss, pulmonary hemorrhage, and viral load were all highly correlated disease phenotypes. We identified a quantitative trait locus of major effect on chromosome 18 (27.1-58.6 Mb) which affected weight loss, viral titer and hemorrhage. Additionally, each of these three phenotypes had distinct quantitative trait loci [Chr 9 (weight loss), Chrs 7 and 12 (virus titer), and Chr 15 (hemorrhage)]. We identified Ticam2, an adaptor protein in the TLR signaling pathways, as a candidate driving differential disease at the Chr 18 locus. Ticam2-/- mice were highly susceptible to SARS-CoV infection, exhibiting increased weight loss and more pulmonary hemorrhage than control mice. These results indicate a critical role for Ticam2 in SARS-CoV disease, and highlight the importance of host genetic variation in disease responses. Copyright © 2017 Gralinski et al.

  2. Unraveling the complexities of the interferon response during SARS-CoV infection

    NARCIS (Netherlands)

    A. de Lang (Anna); T. Baas (Tracey); S.L. Smits (Saskia); M.G. Katze (Michael); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart)

    2009-01-01

    textabstractViruses employ different strategies to circumvent the antiviral actions of the innate immune response. SARS coronavirus (SARS-CoV), a virus that causes severe lung damage encodes an array of proteins able to inhibit induction and signaling of type-I interferons. However, recent studies

  3. Genotype analysis of ORF 62 identifies varicella-zoster virus infections caused by a vaccine strain in children.

    Science.gov (United States)

    Kwak, Byung Ok; Lee, Hoan Jong; Kang, Hyun Mi; Oh, Chi Eun; Choi, Eun Hwa

    2017-06-01

    This study was performed to differentiate vaccine-type strains from wild-type strains and determine the genotype of varicella-zoster virus (VZV) in 51 Korean children. A sequencing analysis of ORF 62 identified two cases of herpes zoster caused by the vaccine-type virus, without a previous history of varicella, 22 months and 5 months after VZV vaccination. The wild-type strain was identified in the remaining children. A genotype analysis of ORF 22 amino acids revealed genotype J in all children except one. Genotype E was identified in an infant with varicella imported from Egypt.

  4. RECOVIR: An application package to automatically identify some single stranded RNA viruses using capsid protein residues that uniquely distinguish among these viruses

    Directory of Open Access Journals (Sweden)

    Fox George E

    2007-10-01

    Full Text Available Abstract Background Most single stranded RNA (ssRNA viruses mutate rapidly to generate large number of strains having highly divergent capsid sequences. Accurate strain recognition in uncharacterized target capsid sequences is essential for epidemiology, diagnostics, and vaccine development. Strain recognition based on similarity scores between target sequences and sequences of homology matched reference strains is often time consuming and ambiguous. This is especially true if only partial target sequences are available or if different ssRNA virus families are jointly analyzed. In such cases, knowledge of residues that uniquely distinguish among known reference strains is critical for rapid and unambiguous strain identification. Conventional sequence comparisons are unable to identify such capsid residues due to high sequence divergence among the ssRNA virus reference strains. Consequently, automated general methods to reliably identify strains using strain distinguishing residues are not currently available. Results We present here RECOVIR ("recognize viruses", a software tool to automatically detect strains of caliciviruses and picornaviruses by comparing their capsid residues with built-in databases of residues that uniquely distinguish among known reference strains of these viruses. The databases were created by constructing partitioned phylogenetic trees of complete capsid sequences of these viruses. Strains were correctly identified for more than 300 complete and partial target sequences by comparing the database residues with the aligned residues of these sequences. It required about 5 seconds of real time to process each sequence. A Java-based user interface coupled with Perl-coded computational modules ensures high portability of the software. RECOVIR currently runs on Windows XP and Linux platforms. The software generalizes a manual method briefly outlined earlier for human caliciviruses. Conclusion This study shows implementation of

  5. FluShuffle and FluResort: new algorithms to identify reassorted strains of the influenza virus by mass spectrometry

    Directory of Open Access Journals (Sweden)

    Lun Aaron TL

    2012-08-01

    Full Text Available Abstract Background Influenza is one of the oldest and deadliest infectious diseases known to man. Reassorted strains of the virus pose the greatest risk to both human and animal health and have been associated with all pandemics of the past century, with the possible exception of the 1918 pandemic, resulting in tens of millions of deaths. We have developed and tested new computer algorithms, FluShuffle and FluResort, which enable reassorted viruses to be identified by the most rapid and direct means possible. These algorithms enable reassorted influenza, and other, viruses to be rapidly identified to allow prevention strategies and treatments to be more efficiently implemented. Results The FluShuffle and FluResort algorithms were tested with both experimental and simulated mass spectra of whole virus digests. FluShuffle considers different combinations of viral protein identities that match the mass spectral data using a Gibbs sampling algorithm employing a mixed protein Markov chain Monte Carlo (MCMC method. FluResort utilizes those identities to calculate the weighted distance of each across two or more different phylogenetic trees constructed through viral protein sequence alignments. Each weighted mean distance value is normalized by conversion to a Z-score to establish a reassorted strain. Conclusions The new FluShuffle and FluResort algorithms can correctly identify the origins of influenza viral proteins and the number of reassortment events required to produce the strains from the high resolution mass spectral data of whole virus proteolytic digestions. This has been demonstrated in the case of constructed vaccine strains as well as common human seasonal strains of the virus. The algorithms significantly improve the capability of the proteotyping approach to identify reassorted viruses that pose the greatest pandemic risk.

  6. Coding algorithms for identifying patients with cirrhosis and hepatitis B or C virus using administrative data.

    Science.gov (United States)

    Niu, Bolin; Forde, Kimberly A; Goldberg, David S

    2015-01-01

    Despite the use of administrative data to perform epidemiological and cost-effectiveness research on patients with hepatitis B or C virus (HBV, HCV), there are no data outside of the Veterans Health Administration validating whether International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes can accurately identify cirrhotic patients with HBV or HCV. The validation of such algorithms is necessary for future epidemiological studies. We evaluated the positive predictive value (PPV) of ICD-9-CM codes for identifying chronic HBV or HCV among cirrhotic patients within the University of Pennsylvania Health System, a large network that includes a tertiary care referral center, a community-based hospital, and multiple outpatient practices across southeastern Pennsylvania and southern New Jersey. We reviewed a random sample of 200 cirrhotic patients with ICD-9-CM codes for HCV and 150 cirrhotic patients with ICD-9-CM codes for HBV. The PPV of 1 inpatient or 2 outpatient HCV codes was 88.0% (168/191, 95% CI: 82.5-92.2%), while the PPV of 1 inpatient or 2 outpatient HBV codes was 81.3% (113/139, 95% CI: 73.8-87.4%). Several variations of the primary coding algorithm were evaluated to determine if different combinations of inpatient and/or outpatient ICD-9-CM codes could increase the PPV of the coding algorithm. ICD-9-CM codes can identify chronic HBV or HCV in cirrhotic patients with a high PPV and can be used in future epidemiologic studies to examine disease burden and the proper allocation of resources. Copyright © 2014 John Wiley & Sons, Ltd.

  7. SARS - infectious disease of 21st century

    Directory of Open Access Journals (Sweden)

    Tjandra Y. Aditama

    2005-03-01

    Full Text Available Severe acute respiratory syndrome (SARS is an emerging viral infectious disease. According to the World Health Organization, a suspected case of SARS is defined as documented fever (temperature >38°C, lower respiratory tract symptoms, and contact with a person believed to have had SARS or history of travel to an area of documented transmission. A probable case is a suspected case with chest radiographic findings of pneumonia, acute respiratory distress syndrome (ARDS, or an unexplained respiratory illness resulting in death, with autopsy findings of ARDS without identifiable cause. In this article some SARS epidemiological data in Indonesia will also presented. There are 7 SARS suspected cases and 2 probable cases were registered in Indonesia on the period of 1 March to 9 July 2003, and no more cases were reported after that time. How will be SARS progression in the future will be a subject of discussion among scientist, and we will have to wait and be prepared for any development might occur. (Med J Indones 2005; 14: 59-63Keywords: SARS, Case Definition, Etiology, Indonesia

  8. A novel, highly divergent ssDNA virus identified in Brazil infecting apple, pear and grapevine.

    Science.gov (United States)

    Basso, Marcos Fernando; da Silva, José Cleydson Ferreira; Fajardo, Thor Vinícius Martins; Fontes, Elizabeth Pacheco Batista; Zerbini, Francisco Murilo

    2015-12-02

    Fruit trees of temperate and tropical climates are of great economical importance worldwide and several viruses have been reported affecting their productivity and longevity. Fruit trees of different Brazilian regions displaying virus-like symptoms were evaluated for infection by circular DNA viruses. Seventy-four fruit trees were sampled and a novel, highly divergent, monopartite circular ssDNA virus was cloned from apple, pear and grapevine trees. Forty-five complete viral genomes were sequenced, with a size of approx. 3.4 kb and organized into five ORFs. Deduced amino acid sequences showed identities in the range of 38% with unclassified circular ssDNA viruses, nanoviruses and alphasatellites (putative Replication-associated protein, Rep), and begomo-, curto- and mastreviruses (putative coat protein, CP, and movement protein, MP). A large intergenic region contains a short palindromic sequence capable of forming a hairpin-like structure with the loop sequence TAGTATTAC, identical to the conserved nonanucleotide of circoviruses, nanoviruses and alphasatellites. Recombination events were not detected and phylogenetic analysis showed a relationship with circo-, nano- and geminiviruses. PCR confirmed the presence of this novel ssDNA virus in field plants. Infectivity tests using the cloned viral genome confirmed its ability to infect apple and pear tree seedlings, but not Nicotiana benthamiana. The name "Temperate fruit decay-associated virus" (TFDaV) is proposed for this novel virus. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Severe acute respiratory syndrome (SARS)

    Science.gov (United States)

    SARS; Respiratory failure - SARS ... Complications may include: Respiratory failure Liver failure Heart failure ... 366. McIntosh K, Perlman S. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). ...

  10. The first human case of neuroinvasive West Nile virus infection identified in Cyprus.

    Science.gov (United States)

    Paphitou, Niki I; Tourvas, Aristomenis; Floridou, Dora; Richter, Jan; Tryfonos, Christina; Christodoulou, Christina

    West Nile virus infection can pose a diagnostic challenge to clinicians, especially in geographic areas where human cases of this disease have never been encountered before. In August 2016, the first human case of West Nile virus infection was diagnosed in Cyprus. An elderly non immunosuppressed patient with a history of recent travel, presented with a clinical picture of rapidly progressing ascending paralysis mimicking Guillain-Barré syndrome. Neuroinvasive West Nile virus disease was diagnosed by detecting West Nile virus nucleic acid in the patient's cerebrospinal fluid. Public health measures were taken raising awareness regarding this disease and its prevention. Clinical vigilance to consider West Nile virus as a possible emerging pathogen in the appropriate clinical setting is warranted and could benefit individual patients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. A Newly Identified Natural Splice Variant ASN Enhances Hepatitis B Virus Amplification.

    Science.gov (United States)

    Zhang, Xiumin; Zhu, Sibo; Zhu, Wei; Li, Aijun; Zhu, Naishuo

    2016-01-01

    Chronic hepatitis B virus (HBV) infection causes approximately one-third of all the cases of liver cirrhosis and more than three-quarters of hepatocellular carcinoma (HCC) worldwide. There are eight different genotypes (A-H) of HBV, among which B and C are the major types of HBV in China. There is a positive correlation between viral load and level of viral splicing variants and the high risk of HCC. The aim of this study was to investigate the splicing variants of HBV circulating in HCC patients. Twenty-four carcinoma and adjacent liver tissues collected from HCC patients were studied. Using reverse transcription-polymerase chain reaction (RT-PCR) and sequencing, we identified a new type of natural splice variant with nucleotides 2448-489 and 910-2120 deleted, and we named it ASN. We also found that a higher viral load and splicing variant level existed in liver carcinoma tissues compared to paracarcinoma tissues. In the investigation of our splicing variant, we found its enhancing effect on HBV replication in vitro. Although splicing variants are not essential for the replication of HBV, they may have an important influence.

  12. Risk Factors Associated With the Ophthalmoscopic Findings Identified in Infants With Presumed Zika Virus Congenital Infection.

    Science.gov (United States)

    Ventura, Camila V; Maia, Mauricio; Travassos, Simone B; Martins, Thayze T; Patriota, Felipe; Nunes, Marcos Eugênio; Agra, Cristiana; Torres, Virginia L; van der Linden, Vanessa; Ramos, Regina C; Rocha, Maria Ângela W; Silva, Paula S; Ventura, Liana O; Belfort, Rubens

    2016-08-01

    The Zika virus (ZIKV) might cause microcephaly and ophthalmoscopic findings in infants of mothers infected during pregnancy. To assess and identify possible risk factors for ophthalmoscopic findings in infants born with microcephaly and a presumed clinical diagnosis of ZIKV intrauterine infection. We conducted a cross-sectional study at the Altino Ventura Foundation in Recife, Brazil, that included 40 infants with microcephaly born in Pernambuco state, Brazil, between May and December 2015. Toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus were ruled out in all of them. Testing of cerebrospinal fluid for ZIKV using IgM antibody-capture enzyme-linked immunosorbent assay was performed in 24 of 40 infants (60.0%). The infants and mothers underwent ocular examinations. The infants were divided into 2 groups, those with and without ophthalmoscopic alterations, for comparison. Identification of risk factors for ophthalmoscopic findings in infants born with microcephaly and ZIKV intrauterine infection. Among the 40 infants, the mean (SD) age was 2.2 (1.2) months (range, 0.1-7.3 months). Of the 24 infants tested, 100% had positive results for ZIKV infection: 14 of 22 infants (63.6%) from the group with ophthalmoscopic findings and 10 of 18 infants (55.6%) from the group without ophthalmoscopic findings. The major symptoms reported in both groups were rash by 26 mothers (65.0%), fever by 9 mothers (22.5%), headache by 9 mothers (22.5%), and arthralgia by 8 mothers (20.0%). No mothers reported conjunctivitis or other ocular symptoms during pregnancy or presented signs of uveitis at the time of examination. Thirty-seven eyes (46.3%) of 22 infants (55.0%) had ophthalmoscopic alterations. Ten mothers (71.4%) of infants with ocular findings reported symptoms during the first trimester (frequency, 0.48; 95% CI, 0.02-0.67; P = .04). A difference was also observed between the groups of infants with and without ocular findings regarding the

  13. Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection.

    Science.gov (United States)

    Ng, Oi-Wing; Chia, Adeline; Tan, Anthony T; Jadi, Ramesh S; Leong, Hoe Nam; Bertoletti, Antonio; Tan, Yee-Joo

    2016-04-12

    Severe acute respiratory syndrome (SARS) is a highly contagious infectious disease which first emerged in late 2002, caused by a then novel human coronavirus, SARS coronavirus (SARS-CoV). The virus is believed to have originated from bats and transmitted to human through intermediate animals such as civet cats. The re-emergence of SARS-CoV remains a valid concern due to the continual persistence of zoonotic SARS-CoVs and SARS-like CoVs (SL-CoVs) in bat reservoirs. In this study, the screening for the presence of SARS-specific T cells in a cohort of three SARS-recovered individuals at 9 and 11 years post-infection was carried out, and all memory T cell responses detected target the SARS-CoV structural proteins. Two CD8(+) T cell responses targeting the SARS-CoV membrane (M) and nucleocapsid (N) proteins were characterized by determining their HLA restriction and minimal T cell epitope regions. Furthermore, these responses were found to persist up to 11 years post-infection. An absence of cross-reactivity of these CD8(+) T cell responses against the newly-emerged Middle East respiratory syndrome coronavirus (MERS-CoV) was also demonstrated. The knowledge of the persistence of SARS-specific celullar immunity targeting the viral structural proteins in SARS-recovered individuals is important in the design and development of SARS vaccines, which are currently unavailable. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Phylogeny of geminivirus coat protein sequences and digital PCR aid in identifying Spissistilus festinus (Say) as a vector of Grapevine red blotch-associated virus

    Science.gov (United States)

    Grapevine red blotch-associated virus (GRBaV) is a newly identified virus of grapevines, and a putative member of a new genus within the family Geminiviridae. This virus is associated with red blotch disease that was first reported in California in 2008. It affects the profitability of vineyards by ...

  15. Receptor recognition and cross-species infections of SARS coronavirus

    Science.gov (United States)

    Li, Fang

    2013-01-01

    Receptor recognition is a major determinant of the host range, cross-species infections, and pathogenesis of the severe acute respiratory syndrome coronavirus (SARS-CoV). A defined receptor-binding domain (RBD) in the SARS-CoV spike protein specifically recognizes its host receptor, angiotensin-converting enzyme 2 (ACE2). This article reviews the latest knowledge about how RBDs from different SARS-CoV strains interact with ACE2 from several animal species. Detailed research on these RBD/ACE2 interactions has established important principles on host receptor adaptations, cross-species infections, and future evolution of SARS-CoV. These principles may apply to other emerging animal viruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV). This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.” PMID:23994189

  16. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.

    Science.gov (United States)

    Menachery, Vineet D; Yount, Boyd L; Debbink, Kari; Agnihothram, Sudhakar; Gralinski, Lisa E; Plante, Jessica A; Graham, Rachel L; Scobey, Trevor; Ge, Xing-Yi; Donaldson, Eric F; Randell, Scott H; Lanzavecchia, Antonio; Marasco, Wayne A; Shi, Zhengli-Li; Baric, Ralph S

    2015-12-01

    The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.

  17. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research.

    Science.gov (United States)

    Simmons, Graham; Zmora, Pawel; Gierer, Stefanie; Heurich, Adeline; Pöhlmann, Stefan

    2013-12-01

    The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses.'' Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research

    Science.gov (United States)

    Simmons, Graham; Zmora, Pawel; Gierer, Stefanie; Heurich, Adeline; Pöhlmann, Stefan

    2013-01-01

    The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.” PMID:24121034

  19. A real-time PCR assay for bat SARS-like coronavirus detection and its application to Italian greater horseshoe bat faecal sample surveys.

    Science.gov (United States)

    Balboni, Andrea; Gallina, Laura; Palladini, Alessandra; Prosperi, Santino; Battilani, Mara

    2012-01-01

    Bats are source of coronaviruses closely related to the severe acute respiratory syndrome (SARS) virus. Numerous studies have been carried out to identify new bat viruses related to SARS-coronavirus (bat-SARS-like CoVs) using a reverse-transcribed-polymerase chain reaction assay. However, a qualitative PCR could underestimate the prevalence of infection, affecting the epidemiological evaluation of bats in viral ecology. In this work an SYBR Green-real time PCR assay was developed for diagnosing infection with SARS-related coronaviruses from bat guano and was applied as screening tool in a survey carried out on 45 greater horseshoe bats (Rhinolophus ferrumequinum) sampled in Italy in 2009. The assay showed high sensitivity and reproducibility. Its application on bats screening resulted in a prevalence of 42%. This method could be suitable as screening tool in epidemiological surveys about the presence of bat-SARS-like CoVs, consequently to obtain a more realistic scenario of the viral prevalence in the population.

  20. A Real-Time PCR Assay for Bat SARS-Like Coronavirus Detection and Its Application to Italian Greater Horseshoe Bat Faecal Sample Surveys

    Directory of Open Access Journals (Sweden)

    Andrea Balboni

    2012-01-01

    Full Text Available Bats are source of coronaviruses closely related to the severe acute respiratory syndrome (SARS virus. Numerous studies have been carried out to identify new bat viruses related to SARS-coronavirus (bat-SARS-like CoVs using a reverse-transcribed-polymerase chain reaction assay. However, a qualitative PCR could underestimate the prevalence of infection, affecting the epidemiological evaluation of bats in viral ecology. In this work an SYBR Green-real time PCR assay was developed for diagnosing infection with SARS-related coronaviruses from bat guano and was applied as screening tool in a survey carried out on 45 greater horseshoe bats (Rhinolophus ferrumequinum sampled in Italy in 2009. The assay showed high sensitivity and reproducibility. Its application on bats screening resulted in a prevalence of 42%. This method could be suitable as screening tool in epidemiological surveys about the presence of bat-SARS-like CoVs, consequently to obtain a more realistic scenario of the viral prevalence in the population.

  1. SARS Pathogenesis: Host Factors

    NARCIS (Netherlands)

    A. de Lang (Anna)

    2012-01-01

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

  2. SARS-unique fold in the Rousettus bat coronavirus HKU9.

    Science.gov (United States)

    Hammond, Robert G; Tan, Xuan; Johnson, Margaret A

    2017-09-01

    The coronavirus nonstructural protein 3 (nsp3) is a multifunctional protein that comprises multiple structural domains. This protein assists viral polyprotein cleavage, host immune interference, and may play other roles in genome replication or transcription. Here, we report the solution NMR structure of a protein from the "SARS-unique region" of the bat coronavirus HKU9. The protein contains a frataxin fold or double-wing motif, which is an α + β fold that is associated with protein/protein interactions, DNA binding, and metal ion binding. High structural similarity to the human severe acute respiratory syndrome (SARS) coronavirus nsp3 is present. A possible functional site that is conserved among some betacoronaviruses has been identified using bioinformatics and biochemical analyses. This structure provides strong experimental support for the recent proposal advanced by us and others that the "SARS-unique" region is not unique to the human SARS virus, but is conserved among several different phylogenetic groups of coronaviruses and provides essential functions. © 2017 The Protein Society.

  3. Peptide Mimicrying Between SARS Coronavirus Spike Protein and Human Proteins Reacts with SARS Patient Serum

    Directory of Open Access Journals (Sweden)

    K.-Y. Hwa

    2008-01-01

    Full Text Available Molecular mimicry, defined as similar structures shared by molecules from dissimilar genes or proteins, is a general strategy used by pathogens to infect host cells. Severe acute respiratory syndrome (SARS is a new human respiratory infectious disease caused by SARS coronavirus (SARS-CoV. The spike (S protein of SARS-CoV plays an important role in the virus entry into a cell. In this study, eleven synthetic peptides from the S protein were selected based on its sequence homology with human proteins. Two of the peptides D07 (residues 927–937 and D08 (residues 942–951 were recognized by the sera of SARS patients. Murine hyperimmune sera against these peptides bound to proteins of human lung epithelial cells A549. Another peptide D10 (residues 490–502 stimulated A549 to proliferate and secrete IL-8. The present results suggest that the selected S protein regions, which share sequence homology with human proteins, may play important roles in SARS-CoV infection.

  4. Case control study to identify risk factors for acute hepatitis C virus infection in Egypt

    Directory of Open Access Journals (Sweden)

    Kandeel Amr M

    2012-11-01

    Full Text Available Abstract Background Identification of risk factors of acute hepatitis C virus (HCV infection in Egypt is crucial to develop appropriate prevention strategies. Methods We conducted a case–control study, June 2007-September 2008, to investigate risk factors for acute HCV infection in Egypt among 86 patients and 287 age and gender matched controls identified in two infectious disease hospitals in Cairo and Alexandria. Case-patients were defined as: any patient with symptoms of acute hepatitis; lab tested positive for HCV antibodies and negative for HBsAg, HBc IgM, HAV IgM; and 7-fold increase in the upper limit of transaminase levels. Controls were selected from patients’ visitors with negative viral hepatitis markers. Subjects were interviewed about previous exposures within six months, including community-acquired and health-care associated practices. Results Case-patients were more likely than controls to have received injection with a reused syringe (OR=23.1, CI 4.7-153, to have been in prison (OR=21.5, CI 2.5-479.6, to have received IV fluids in a hospital (OR=13.8, CI 5.3-37.2, to have been an IV drug user (OR=12.1, CI 4.6-33.1, to have had minimal surgical procedures (OR=9.7, CI 4.2-22.4, to have received IV fluid as an outpatient (OR=8, CI 4–16.2, or to have been admitted to hospital (OR=7.9, CI 4.2-15 within the last 6 months. Multivariate analysis indicated that unsafe health facility practices are the main risk factors associated with transmission of HCV infection in Egypt. Conclusion In Egypt, focusing acute HCV prevention measures on health-care settings would have a beneficial impact.

  5. SARS: Key factors in crisis management.

    Science.gov (United States)

    Tseng, Hsin-Chao; Chen, Thai-Form; Chou, Shieu-Ming

    2005-03-01

    This study was conducted at a single hospital selected in Taipei during the SARS (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan. During this period of time, 104 SARS patients were admitted to the hospital. There were no negative reports related to the selected hospital despite its being located right in the center of an area struck by the epidemic. The purpose of this study was to identify the key factors enabling the hospital to survive SARS unscathed. Data were collected from in-depth interviews with the nursing directors and nursing managers of the SARS units, along with a review of relevant hospital documents. The five key elements identified as survival factors during this SARS crisis are as follows: 1. good control of timing for crisis management, 2. careful decision-making, 3. thorough implementation, 4. effective communication, and 5. trust between management and employees. The results of this study reconfirmed the selected hospital as a model for good crisis management during the SARS epidemic.

  6. Evolution and Variation of the SARS-CoV Genome

    OpenAIRE

    Hu, Jianfei; Wang, Jing; Xu, Jing; Li, Wei; Han, Yujun; Li, Yan; Ji, Jia; Ye, Jia; Xu, Zhao; Zhang, Zizhang; Wei, Wei; Li, Songgang; Wang, Jun; Wang, Jian; Yu, Jun

    2016-01-01

    Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their rich...

  7. Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination.

    Science.gov (United States)

    Lau, Susanna K P; Feng, Yun; Chen, Honglin; Luk, Hayes K H; Yang, Wei-Hong; Li, Kenneth S M; Zhang, Yu-Zhen; Huang, Yi; Song, Zhi-Zhong; Chow, Wang-Ngai; Fan, Rachel Y Y; Ahmed, Syed Shakeel; Yeung, Hazel C; Lam, Carol S F; Cai, Jian-Piao; Wong, Samson S Y; Chan, Jasper F W; Yuen, Kwok-Yung; Zhang, Hai-Lin; Woo, Patrick C Y

    2015-10-01

    Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8

  8. Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination

    Science.gov (United States)

    Lau, Susanna K. P.; Feng, Yun; Chen, Honglin; Luk, Hayes K. H.; Yang, Wei-Hong; Li, Kenneth S. M.; Zhang, Yu-Zhen; Huang, Yi; Song, Zhi-Zhong; Chow, Wang-Ngai; Fan, Rachel Y. Y.; Ahmed, Syed Shakeel; Yeung, Hazel C.; Lam, Carol S. F.; Cai, Jian-Piao; Wong, Samson S. Y.; Chan, Jasper F. W.; Yuen, Kwok-Yung

    2015-01-01

    ABSTRACT Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS

  9. Understanding the T cell immune response in SARS coronavirus infection.

    Science.gov (United States)

    Janice Oh, Hsueh-Ling; Ken-En Gan, Samuel; Bertoletti, Antonio; Tan, Yee-Joo

    2012-09-01

    The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development.

  10. Understanding the T cell immune response in SARS coronavirus infection

    Science.gov (United States)

    Janice Oh, Hsueh-Ling; Ken-En Gan, Samuel; Bertoletti, Antonio; Tan, Yee-Joo

    2012-01-01

    The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development. PMID:26038429

  11. Literature-Related Discovery: Potential Treatments and Preventives for SARS

    Science.gov (United States)

    2010-01-01

    vesicular stomatitis virus ( VSV ) production in vitro. The extracts selected strongly inhibited MHV replication and could be potential candidates for new...Southern China (Guangdong Province, Fall 2002) and subsequent cross-species transmission of SARS-CoV to humans; 4) transmission of the virus through...both non-hospital personal contact and hospital staff contact; and, 5) global transmission of the virus via travelers from affected regions in Asia

  12. Analysis of the nucleoprotein gene identifies three distinct lineages of viral haemorrhagic septicemia virus (VHSV) within the European marine environment

    Science.gov (United States)

    Snow, M.; Cunningham, C.O.; Melvin, W.T.; Kurath, G.

    1999-01-01

    A ribonuclease (RNase) protection assay (RPA) has been used to detect nucleotide sequence variation within the nucleoprotein gene of 39 viral haemorrhagic septicaemia virus (VHSV) isolates of European marine origin. The classification of VHSV isolates based on RPA cleavage patterns permitted the identification of ten distinct groups of viruses based on differences at the molecular level. The nucleotide sequence of representatives of each of these groupings was determined and subjected to phylogenetic analysis. This revealed grouping of the European marine isolates of VHSV into three genotypes circulating within distinct geographic areas. A fourth genotype was identified comprising isolates originating from North America. Phylogenetic analyses indicated that VHSV isolates recovered from wild caught fish around the British Isles were genetically related to isolates responsible for losses in farmed turbot. Furthermore, a relationship between naturally occurring marine isolates and VHSV isolates causing mortality among rainbow trout in continental Europe was demonstrated. Analysis of the nucleoprotein gene identifies distinct lineages of viral haemorrhagic septicaemia virus within the European marine environment. Virus Res. 63, 35-44. Available from: 

  13. Genome sequence of erythromelalgia-related poxvirus identifies it as an ectromelia virus strain.

    Directory of Open Access Journals (Sweden)

    Jorge D Mendez-Rios

    Full Text Available Erythromelagia is a condition characterized by attacks of burning pain and inflammation in the extremeties. An epidemic form of this syndrome occurs in secondary students in rural China and a virus referred to as erythromelalgia-associated poxvirus (ERPV was reported to have been recovered from throat swabs in 1987. Studies performed at the time suggested that ERPV belongs to the orthopoxvirus genus and has similarities with ectromelia virus, the causative agent of mousepox. We have determined the complete genome sequence of ERPV and demonstrated that it has 99.8% identity to the Naval strain of ectromelia virus and a slighly lower identity to the Moscow strain. Small DNA deletions in the Naval genome that are absent from ERPV may suggest that the sequenced strain of Naval was not the immediate progenitor of ERPV.

  14. Affinity purification combined with mass spectrometry to identify herpes simplex virus protein-protein interactions.

    Science.gov (United States)

    Meckes, David G

    2014-01-01

    The identification and characterization of herpes simplex virus protein interaction complexes are fundamental to understanding the molecular mechanisms governing the replication and pathogenesis of the virus. Recent advances in affinity-based methods, mass spectrometry configurations, and bioinformatics tools have greatly increased the quantity and quality of protein-protein interaction datasets. In this chapter, detailed and reliable methods that can easily be implemented are presented for the identification of protein-protein interactions using cryogenic cell lysis, affinity purification, trypsin digestion, and mass spectrometry.

  15. SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme.

    Science.gov (United States)

    Békés, Miklós; Rut, Wioletta; Kasperkiewicz, Paulina; Mulder, Monique P C; Ovaa, Huib; Drag, Marcin; Lima, Christopher D; Huang, Tony T

    2015-06-01

    Ubiquitin (Ub) and the Ub-like (Ubl) modifier interferon-stimulated gene 15 (ISG15) participate in the host defence of viral infections. Viruses, including the severe acute respiratory syndrome human coronavirus (SARS hCoV), have co-opted Ub-ISG15 conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub-ISG15-conjugated host proteins. In the present study, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle East respiratory syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that, similar to SARS PLpro, MERS PLpro is both a deubiquitinating (DUB) and a deISGylating enzyme. Further analysis of the intrinsic DUB activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, whereas SARS PLpro prefers to cleave Lys48-linked polyUb chains. Secondly, MERS PLpro cleaves polyUb chains in a 'mono-distributive' manner (one Ub at a time) and SARS PLpro prefers to cleave Lys48-linked polyUb chains by sensing a di-Ub moiety as a minimal recognition element using a 'di-distributive' cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP (Ub-specific protease)-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help to identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses.

  16. SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme

    Science.gov (United States)

    Békés, Miklós; Rut, Wioletta; Kasperkiewicz, Paulina; Mulder, Monique P. C.; Ovaa, Huib; Drag, Marcin; Lima, Christopher D.; Huang, Tony T.

    2015-01-01

    Ubiquitin (Ub) and the ubiquitin-like modifier interferon stimulated gene 15 (ISG15) participate in the host defense of viral infections. Viruses, including the Severe Acute Respiratory Syndrome human coronavirus (SARS hCoV), have co-opted Ub/ISG15-conjugation pathways for their own advantage or have evolved effector proteins to counter pro-inflammatory properties of Ub/ISG15-conjugated host proteins. Here, we compare substrate specificities of the papain-like protease (PLpro) from the recently emerged Middle Eastern Respiratory Syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through biochemical assays, we show that similar to SARS PLpro, MERS PLpro is both a deubiquitinating and a deISGylating enzyme. Further analysis of the intrinsic deubiquitinating enzyme (DUB) activity of these viral proteases revealed unique differences between the recognition and cleavage specificities of polyUb chains. First, MERS PLpro shows broad linkage specificity for the cleavage of polyUb chains, while SARS PLpro prefers to cleave Lys48-linked polyUb chains. Second, MERS PLpro cleaves polyUb chains in a “mono-distributive” manner (one Ub at a time), and SARS PLpro prefers to cleave K48-linked poly-Ub chains by sensing a di-Ub moiety as a minimal recognition element using a “di-distributive” cleavage mechanism. The di-distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP-family DUBs, as related USP family members from humans do not display such a mechanism. We propose that these intrinsic enzymatic differences between SARS and MERS PLpro will help identify pro-inflammatory substrates of these viral DUBs and can guide in the design of therapeutics to combat infection by coronaviruses. PMID:25764917

  17. Epstein-Barr virus latent gene sequences as geographical markers of viral origin: unique EBNA3 gene signatures identify Japanese viruses as distinct members of the Asian virus family.

    Science.gov (United States)

    Sawada, Akihisa; Croom-Carter, Deborah; Kondo, Osamu; Yasui, Masahiro; Koyama-Sato, Maho; Inoue, Masami; Kawa, Keisei; Rickinson, Alan B; Tierney, Rosemary J

    2011-05-01

    Polymorphisms in Epstein-Barr virus (EBV) latent genes can identify virus strains from different human populations and individual strains within a population. An Asian EBV signature has been defined almost exclusively from Chinese viruses, with little information from other Asian countries. Here we sequenced polymorphic regions of the EBNA1, 2, 3A, 3B, 3C and LMP1 genes of 31 Japanese strains from control donors and EBV-associated T/NK-cell lymphoproliferative disease (T/NK-LPD) patients. Though identical to Chinese strains in their dominant EBNA1 and LMP1 alleles, Japanese viruses were subtly different at other loci. Thus, while Chinese viruses mainly fall into two families with strongly linked 'Wu' or 'Li' alleles at EBNA2 and EBNA3A/B/C, Japanese viruses all have the consensus Wu EBNA2 allele but fall into two families at EBNA3A/B/C. One family has variant Li-like sequences at EBNA3A and 3B and the consensus Li sequence at EBNA3C; the other family has variant Wu-like sequences at EBNA3A, variants of a low frequency Chinese allele 'Sp' at EBNA3B and a consensus Sp sequence at EBNA3C. Thus, EBNA3A/B/C allelotypes clearly distinguish Japanese from Chinese strains. Interestingly, most Japanese viruses also lack those immune-escape mutations in the HLA-A11 epitope-encoding region of EBNA3B that are so characteristic of viruses from the highly A11-positive Chinese population. Control donor-derived and T/NK-LPD-derived strains were similarly distributed across allelotypes and, by using allelic polymorphisms to track virus strains in patients pre- and post-haematopoietic stem-cell transplant, we show that a single strain can induce both T/NK-LPD and B-cell-lymphoproliferative disease in the same patient.

  18. Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks

    Directory of Open Access Journals (Sweden)

    Boucher Charles AB

    2010-07-01

    Full Text Available Abstract Background The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics. Results Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems. Conclusions HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another.

  19. Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins.

    Science.gov (United States)

    Wang, Sheng-Fan; Tseng, Sung-Pin; Yen, Chia-Hung; Yang, Jyh-Yuan; Tsao, Ching-Han; Shen, Chun-Wei; Chen, Kuan-Hsuan; Liu, Fu-Tong; Liu, Wu-Tse; Chen, Yi-Ming Arthur; Huang, Jason C

    2014-08-22

    The severe acute respiratory syndrome coronavirus (SARS-CoV) still carries the potential for reemergence, therefore efforts are being made to create a vaccine as a prophylactic strategy for control and prevention. Antibody-dependent enhancement (ADE) is a mechanism through which dengue viruses, feline coronaviruses, and HIV viruses take advantage of anti-viral humoral immune responses to infect host target cells. Here we describe our observations of SARS-CoV using ADE to enhance the infectivity of a HL-CZ human promonocyte cell line. Quantitative-PCR and immunofluorescence staining results indicate that SARS-CoV is capable of replication in HL-CZ cells, and of displaying virus-induced cytopathic effects and increased levels of TNF-α, IL-4 and IL-6 two days post-infection. According to flow cytometry data, the HL-CZ cells also expressed angiotensin converting enzyme 2 (ACE2, a SARS-CoV receptor) and higher levels of the FcγRII receptor. We found that higher concentrations of anti-sera against SARS-CoV neutralized SARS-CoV infection, while highly diluted anti-sera significantly increased SARS-CoV infection and induced higher levels of apoptosis. Results from infectivity assays indicate that SARS-CoV ADE is primarily mediated by diluted antibodies against envelope spike proteins rather than nucleocapsid proteins. We also generated monoclonal antibodies against SARS-CoV spike proteins and observed that most of them promoted SARS-CoV infection. Combined, our results suggest that antibodies against SARS-CoV spike proteins may trigger ADE effects. The data raise new questions regarding a potential SARS-CoV vaccine, while shedding light on mechanisms involved in SARS pathogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays.

    Directory of Open Access Journals (Sweden)

    Leena Pohjala

    Full Text Available Chikungunya virus (CHIKV, an alphavirus, has recently caused epidemic outbreaks and is therefore considered a re-emerging pathogen for which no effective treatment is available. In this study, a CHIKV replicon containing the virus replicase proteins together with puromycin acetyltransferase, EGFP and Renilla luciferase marker genes was constructed. The replicon was transfected into BHK cells to yield a stable cell line. A non-cytopathic phenotype was achieved by a Pro718 to Gly substitution and a five amino acid insertion within non-structural protein 2 (nsP2, obtained through selection for stable growth. Characterization of the replicon cell line by Northern blotting analysis revealed reduced levels of viral RNA synthesis. The CHIKV replicon cell line was validated for antiviral screening in 96-well format and used for a focused screen of 356 compounds (natural compounds and clinically approved drugs. The 5,7-dihydroxyflavones apigenin, chrysin, naringenin and silybin were found to suppress activities of EGFP and Rluc marker genes expressed by the CHIKV replicon. In a concomitant screen against Semliki Forest virus (SFV, their anti-alphaviral activity was confirmed and several additional inhibitors of SFV with IC₅₀ values between 0.4 and 24 µM were identified. Chlorpromazine and five other compounds with a 10H-phenothiazinyl structure were shown to inhibit SFV entry using a novel entry assay based on a temperature-sensitive SFV mutant. These compounds also reduced SFV and Sindbis virus-induced cytopathic effect and inhibited SFV virion production in virus yield experiments. Finally, antiviral effects of selected compounds were confirmed using infectious CHIKV. In summary, the presented approach for discovering alphaviral inhibitors enabled us to identify potential lead structures for the development of alphavirus entry and replication phase inhibitors as well as demonstrated the usefulness of CHIKV replicon and SFV as biosafe surrogate

  1. Meta-Analysis of Aedes aegypti Expression Datasets: Comparing Virus Infection and Blood-Fed Transcriptomes to Identify Markers of Virus Presence

    Directory of Open Access Journals (Sweden)

    Kiyoshi Ferreira Fukutani

    2018-01-01

    Full Text Available The mosquito Aedes aegypti (L. is vector of several arboviruses including dengue, yellow fever, chikungunya, and more recently zika. Previous transcriptomic studies have been performed to elucidate altered pathways in response to viral infection. However, the intrinsic coupling between alimentation and infection were unappreciated in these studies. Feeding is required for the initial mosquito contact with the virus and these events are highly dependent. Addressing this relationship, we reinterrogated datasets of virus-infected mosquitoes with two different diet schemes (fed and unfed mosquitoes, evaluating the metabolic cross-talk during both processes. We constructed coexpression networks with the differentially expressed genes of these comparison: virus-infected versus blood-fed mosquitoes and virus-infected versus unfed mosquitoes. Our analysis identified one module with 110 genes that correlated with infection status (representing ~0.7% of the A. aegypti genome. Furthermore, we performed a machine-learning approach and summarized the infection status using only four genes (AAEL012128, AAEL014210, AAEL002477, and AAEL005350. While three of the four genes were annotated as hypothetical proteins, AAEL012128 gene is a membrane amino acid transporter correlated with viral envelope binding. This gene alone is able to discriminate all infected samples and thus should have a key role to discriminate viral infection in the A. aegypti mosquito. Moreover, validation using external datasets found this gene as differentially expressed in four transcriptomic experiments. Therefore, these genes may serve as a proxy of viral infection in the mosquito and the others 106 identified genes provides a framework to future studies.

  2. Meta-Analysis ofAedes aegyptiExpression Datasets: Comparing Virus Infection and Blood-Fed Transcriptomes to Identify Markers of Virus Presence.

    Science.gov (United States)

    Fukutani, Kiyoshi Ferreira; Kasprzykowski, José Irahe; Paschoal, Alexandre Rossi; Gomes, Matheus de Souza; Barral, Aldina; de Oliveira, Camila I; Ramos, Pablo Ivan Pereira; de Queiroz, Artur Trancoso Lopo

    2017-01-01

    The mosquito Aedes aegypti (L.) is vector of several arboviruses including dengue, yellow fever, chikungunya, and more recently zika. Previous transcriptomic studies have been performed to elucidate altered pathways in response to viral infection. However, the intrinsic coupling between alimentation and infection were unappreciated in these studies. Feeding is required for the initial mosquito contact with the virus and these events are highly dependent. Addressing this relationship, we reinterrogated datasets of virus-infected mosquitoes with two different diet schemes (fed and unfed mosquitoes), evaluating the metabolic cross-talk during both processes. We constructed coexpression networks with the differentially expressed genes of these comparison: virus-infected versus blood-fed mosquitoes and virus-infected versus unfed mosquitoes. Our analysis identified one module with 110 genes that correlated with infection status (representing ~0.7% of the A. aegypti genome). Furthermore, we performed a machine-learning approach and summarized the infection status using only four genes (AAEL012128, AAEL014210, AAEL002477, and AAEL005350). While three of the four genes were annotated as hypothetical proteins, AAEL012128 gene is a membrane amino acid transporter correlated with viral envelope binding. This gene alone is able to discriminate all infected samples and thus should have a key role to discriminate viral infection in the A. aegypti mosquito. Moreover, validation using external datasets found this gene as differentially expressed in four transcriptomic experiments. Therefore, these genes may serve as a proxy of viral infection in the mosquito and the others 106 identified genes provides a framework to future studies.

  3. Identify-Isolate-Inform: A Tool for Initial Detection and Management of Zika Virus Patients in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Kristi L. Koenig

    2016-05-01

    Full Text Available First isolated in 1947 from a monkey in the Zika forest in Uganda, and from mosquitoes in the same forest the following year, Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. More than one million people have been infected since the appearance of the virus in Brazil in 2015. Approximately 80% of infected patients are asymptomatic. An association with microcephaly and other birth defects as well as Guillain-Barre Syndrome has led to a World Health Organization declaration of Zika virus as a Public Health Emergency of International Concern in February 2016. Zika virus is a vector-borne disease transmitted primarily by the Aedes aegypti mosquito. Male to female sexual transmission has been reported and there is potential for transmission via blood transfusions. After an incubation period of 2-7 days, symptomatic patients develop rapid onset fever, maculopapular rash, arthralgia, and conjunctivitis, often associated with headache and myalgias. Emergency department (ED personnel must be prepared to address concerns from patients presenting with symptoms consistent with acute Zika virus infection, especially those who are pregnant or planning travel to Zika-endemic regions, as well as those women planning to become pregnant and their partners. The identify-isolate-inform (3I tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED, and later adjusted for measles and Middle East Respiratory Syndrome, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for initial detection and management of patients under investigation for Zika virus. Following an assessment of epidemiologic risk, including travel to countries with mosquitoes that transmit Zika virus, patients are further investigated if clinically indicated. If after a rapid evaluation, Zika or other

  4. Identify-Isolate-Inform: A Tool for Initial Detection and Management of Zika Virus Patients in the Emergency Department.

    Science.gov (United States)

    Koenig, Kristi L; Almadhyan, Abdulmajeed; Burns, Michael J

    2016-05-01

    First isolated in 1947 from a monkey in the Zika forest in Uganda, and from mosquitoes in the same forest the following year, Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. More than one million people have been infected since the appearance of the virus in Brazil in 2015. Approximately 80% of infected patients are asymptomatic. An association with microcephaly and other birth defects as well as Guillain-Barre Syndrome has led to a World Health Organization declaration of Zika virus as a Public Health Emergency of International Concern in February 2016. Zika virus is a vector-borne disease transmitted primarily by the Aedes aegypti mosquito. Male to female sexual transmission has been reported and there is potential for transmission via blood transfusions. After an incubation period of 2-7 days, symptomatic patients develop rapid onset fever, maculopapular rash, arthralgia, and conjunctivitis, often associated with headache and myalgias. Emergency department (ED) personnel must be prepared to address concerns from patients presenting with symptoms consistent with acute Zika virus infection, especially those who are pregnant or planning travel to Zika-endemic regions, as well as those women planning to become pregnant and their partners. The identify-isolate-inform (3I) tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED, and later adjusted for measles and Middle East Respiratory Syndrome, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for initial detection and management of patients under investigation for Zika virus. Following an assessment of epidemiologic risk, including travel to countries with mosquitoes that transmit Zika virus, patients are further investigated if clinically indicated. If after a rapid evaluation, Zika or other arthropod

  5. SARS Requests for Information

    National Research Council Canada - National Science Library

    Rob Hare

    2016-01-01

      It is an increasingly common scenario: the South African Revenue Service (SARS) sends a taxpayer a request for information and, if it does not receive a response, proceeds to issue tax assessments against that taxpayer...

  6. ESTUDIO TEÓRICO DEL VIRUS DEL SÍNDROME RESPIRATORIO AGUDO SEVERO (SARS A TRAVÉS DEL USO DE MÉTODOS DE ACOPLAMIENTO MOLECULAR

    Directory of Open Access Journals (Sweden)

    Ricardo Vivas Reyes

    2010-03-01

    Full Text Available En este estudio se ha evaluado por medio de la metodología de acoplamiento molecular una serie de 5 ligandos borados, que son variantes de la molécula FL-078. Estas moléculas tienen actividad inhibitoria frente a la proteasa Mpro responsable de la replicación del SARS-CoV. Haciendo uso del programa SYBYL7.0 se optimizó el homodímero de la Mpro (código 1Q2W, y a través del software FlexX se hizo el acople molecular con el fin de escoger el confórmero más estable de los ligandos aril borados frente a la macromolécula Mpro, encontrándose que la estructura FL-166 fue la de mejor conformación. Los 5 ligandos aril borados tienen la propiedad de interaccionar con el grupo hidroxilo (OH presente en los residuos tales como serinas, treoninas y tirosinas. Los resultados acople molecular muestran que el mejor acercamiento sobre la cavidad se da sobre el conjunto de treoninas 21, 24, 25 y 26, y no como se afirma en la literatura: que se da sobre el conjunto de serinas 139, 144 y 147.

  7. Human antibody repertoire after VSV-Ebola vaccination identifies novel targets and virus-neutralizing IgM antibodies.

    Science.gov (United States)

    Khurana, Surender; Fuentes, Sandra; Coyle, Elizabeth M; Ravichandran, Supriya; Davey, Richard T; Beigel, John H

    2016-12-01

    Development of an effective vaccine against Ebola virus is of high priority. However, knowledge about potential correlates of protection and the durability of immune response after vaccination is limited. Here, we elucidate the human antibody repertoire after administration of vesicular stomatitis virus (VSV)-Ebola vaccine at 3 million, 20 million and 100 million plaque-forming units (PFU) and homologous VSV-Ebola vaccine boost in healthy adult volunteers. Whole genome-fragment phage display libraries, expressing linear and conformational epitopes of Ebola glycoprotein (GP), showed higher diversity of antibody epitopes in individuals vaccinated with 20 million PFU than in those vaccinated with 3 million or 100 million PFU. Surface plasmon resonance kinetics showed higher levels of GP-binding antibodies after a single vaccination with 20 million or 100 million PFU than with 3 million PFU, and these correlated strongly with neutralization titers. A second vaccination did not boost antibody or virus neutralization titers, which declined rapidly, and induced only minimal antibody affinity maturation. Isotype analysis revealed a predominant IgM response even after the second vaccination, which contributed substantially to virus neutralization in vitro. These findings may help identify new vaccine targets and aid development and evaluation of effective countermeasures against Ebola.

  8. Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry

    Directory of Open Access Journals (Sweden)

    Gisa Gerold

    2015-08-01

    Full Text Available Hepatitis C virus (HCV enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection, as indicated by RNAi. We further characterized serum response factor binding protein 1 (SRFBP1, which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.

  9. Novel circular single-stranded DNA viruses identified in marine invertebrates reveal high sequence diversity and consistent predicted intrinsic disorder patterns within putative structural proteins.

    Science.gov (United States)

    Rosario, Karyna; Schenck, Ryan O; Harbeitner, Rachel C; Lawler, Stephanie N; Breitbart, Mya

    2015-01-01

    Viral metagenomics has recently revealed the ubiquitous and diverse nature of single-stranded DNA (ssDNA) viruses that encode a conserved replication initiator protein (Rep) in the marine environment. Although eukaryotic circular Rep-encoding ssDNA (CRESS-DNA) viruses were originally thought to only infect plants and vertebrates, recent studies have identified these viruses in a number of invertebrates. To further explore CRESS-DNA viruses in the marine environment, this study surveyed CRESS-DNA viruses in various marine invertebrate species. A total of 27 novel CRESS-DNA genomes, with Reps that share less than 60.1% identity with previously reported viruses, were recovered from 21 invertebrate species, mainly crustaceans. Phylogenetic analysis based on the Rep revealed a novel clade of CRESS-DNA viruses that included approximately one third of the marine invertebrate associated viruses identified here and whose members may represent a novel family. Investigation of putative capsid proteins (Cap) encoded within the eukaryotic CRESS-DNA viral genomes from this study and those in GenBank demonstrated conserved patterns of predicted intrinsically disordered regions (IDRs), which can be used to complement similarity-based searches to identify divergent structural proteins within novel genomes. Overall, this study expands our knowledge of CRESS-DNA viruses associated with invertebrates and explores a new tool to evaluate divergent structural proteins encoded by these viruses.

  10. Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype

    Directory of Open Access Journals (Sweden)

    Kimberly A. Dowd

    2016-08-01

    Full Text Available Recent epidemics of Zika virus (ZIKV have been associated with congenital malformation during pregnancy and Guillain-Barré syndrome. There are two ZIKV lineages (African and Asian that share >95% amino acid identity. Little is known regarding the ability of neutralizing antibodies elicited against one lineage to protect against the other. We investigated the breadth of the neutralizing antibody response following ZIKV infection by measuring the sensitivity of six ZIKV strains to neutralization by ZIKV-confirmed convalescent human serum or plasma samples. Contemporary Asian and early African ZIKV strains were similarly sensitive to neutralization regardless of the cellular source of virus. Furthermore, mouse immune serum generated after infection with African or Asian ZIKV strains was capable of neutralizing homologous and heterologous ZIKV strains equivalently. Because our study only defines a single ZIKV serotype, vaccine candidates eliciting robust neutralizing antibody responses should inhibit infection of both ZIKV lineages, including strains circulating in the Americas.

  11. Identifying the environmental conditions favouring West Nile Virus outbreaks in Europe.

    Directory of Open Access Journals (Sweden)

    Matteo Marcantonio

    Full Text Available West Nile Virus (WNV is a globally important mosquito borne virus, with significant implications for human and animal health. The emergence and spread of new lineages, and increased pathogenicity, is the cause of escalating public health concern. Pinpointing the environmental conditions that favour WNV circulation and transmission to humans is challenging, due both to the complexity of its biological cycle, and the under-diagnosis and reporting of epidemiological data. Here, we used remote sensing and GIS to enable collation of multiple types of environmental data over a continental spatial scale, in order to model annual West Nile Fever (WNF incidence across Europe and neighbouring countries. Multi-model selection and inference were used to gain a consensus from multiple linear mixed models. Climate and landscape were key predictors of WNF outbreaks (specifically, high precipitation in late winter/early spring, high summer temperatures, summer drought, occurrence of irrigated croplands and highly fragmented forests. Identification of the environmental conditions associated with WNF outbreaks is key to enabling public health bodies to properly focus surveillance and mitigation of West Nile virus impact, but more work needs to be done to enable accurate predictions of WNF risk.

  12. A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity.

    Science.gov (United States)

    Johansen, Lisa M; DeWald, Lisa Evans; Shoemaker, Charles J; Hoffstrom, Benjamin G; Lear-Rooney, Calli M; Stossel, Andrea; Nelson, Elizabeth; Delos, Sue E; Simmons, James A; Grenier, Jill M; Pierce, Laura T; Pajouhesh, Hassan; Lehár, Joseph; Hensley, Lisa E; Glass, Pamela J; White, Judith M; Olinger, Gene G

    2015-06-03

    Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections. Copyright © 2015, American Association for the Advancement of Science.

  13. Identifying protective host gene expression signatures within the spleen during West Nile virus infection in the collaborative cross model

    Directory of Open Access Journals (Sweden)

    Richard Green

    2016-12-01

    Full Text Available Flaviviruses are hematophagous arthropod-viruses that pose global challenges to human health. Like Zika virus, West Nile Virus (WNV is a flavivirus for which no approved vaccine exists [1]. The role host genetics play in early detection and response to WNV still remains largely unexplained. In order to capture the impact of genetic variation on innate immune responses, we studied gene expression following WNV infection using the collaborative cross (CC. The CC is a mouse genetics resource composed of hundreds of independently bred, octo-parental recombinant inbred mouse lines [2]. To accurately capture the host immune gene expression signatures of West Nile infection, we used the nanostring platform to evaluate expression in spleen tissue isolated from CC mice infected with WNV over a time course of 4, 7, and 12 days' post-infection [3]. Nanostring is a non-amplification based digital method to quantitate gene expression that uses color-coded molecular barcodes to detect hundreds of transcripts in a sample. Using this approach, we identified unique gene signatures in spleen tissue at days 4, 7, and 12 following WNV infection, which delineated distinct differences between asymptomatic and symptomatic CC lines. We also identified novel immune genes. Data was deposited into the Gene Expression Omnibus under accession GSE86000.

  14. Identifying protective host gene expression signatures within the spleen during West Nile virus infection in the collaborative cross model.

    Science.gov (United States)

    Green, Richard; Wilkins, Courtney; Thomas, Sunil; Sekine, Aimee; Ireton, Renee C; Ferris, Martin T; Hendrick, Duncan M; Voss, Kathleen; de Villena, Fernando Pardo-Manuel; Baric, Ralph; Heise, Mark; Gale, Michael

    2016-12-01

    Flaviviruses are hematophagous arthropod-viruses that pose global challenges to human health. Like Zika virus, West Nile Virus (WNV) is a flavivirus for which no approved vaccine exists [1]. The role host genetics play in early detection and response to WNV still remains largely unexplained. In order to capture the impact of genetic variation on innate immune responses, we studied gene expression following WNV infection using the collaborative cross (CC). The CC is a mouse genetics resource composed of hundreds of independently bred, octo-parental recombinant inbred mouse lines [2]. To accurately capture the host immune gene expression signatures of West Nile infection, we used the nanostring platform to evaluate expression in spleen tissue isolated from CC mice infected with WNV over a time course of 4, 7, and 12 days' post-infection [3]. Nanostring is a non-amplification based digital method to quantitate gene expression that uses color-coded molecular barcodes to detect hundreds of transcripts in a sample. Using this approach, we identified unique gene signatures in spleen tissue at days 4, 7, and 12 following WNV infection, which delineated distinct differences between asymptomatic and symptomatic CC lines. We also identified novel immune genes. Data was deposited into the Gene Expression Omnibus under accession GSE86000.

  15. The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors.

    Directory of Open Access Journals (Sweden)

    Susanne Pfefferle

    2011-10-01

    Full Text Available Coronaviruses (CoVs are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS in 2002/2003 has demonstrated human vulnerability to (Coronavirus CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B as interaction partners of the CoV non-structural protein 1 (Nsp1. These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock.

  16. Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Leticia Barboza Rocha

    2017-10-01

    Full Text Available Dengue nonstructural protein 1 (NS1 is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal antibodies against recombinant NS1 protein from dengue virus serotype 2 (DENV2, which were used to map three NS1 epitopes. The sequence 193AVHADMGYWIESALNDT209 was recognized by monoclonal antibodies 2H5 and 4H1BC, which also cross-reacted with Zika virus (ZIKV protein. On the other hand, the sequence 25VHTWTEQYKFQPES38 was recognized by mAb 4F6 that did not cross react with ZIKV. Lastly, a previously unidentified DENV2 NS1-specific epitope, represented by the sequence 127ELHNQTFLIDGPETAEC143, is described in the present study after reaction with mAb 4H2, which also did not cross react with ZIKV. The selection and characterization of the epitope, specificity of anti-NS1 mAbs, may contribute to the development of diagnostic tools able to differentiate DENV and ZIKV infections.

  17. Identification of phosphorylation sites in the nucleocapsid protein (N protein) of SARS-coronavirus

    Science.gov (United States)

    Lin, Liang; Shao, Jianmin; Sun, Maomao; Liu, Jinxiu; Xu, Gongjin; Zhang, Xumin; Xu, Ningzhi; Wang, Rong; Liu, Siqi

    2007-12-01

    After decoding the genome of SARS-coronavirus (SARS-CoV), next challenge is to understand how this virus causes the illness at molecular bases. Of the viral structural proteins, the N protein plays a pivot role in assembly process of viral particles as well as viral replication and transcription. The SARS-CoV N proteins expressed in the eukaryotes, such as yeast and HEK293 cells, appeared in the multiple spots on two-dimensional electrophoresis (2DE), whereas the proteins expressed in E. coli showed a single 2DE spotE These 2DE spots were further examined by Western blot and MALDI-TOF/TOF MS, and identified as the N proteins with differently apparent pI values and similar molecular mass of 50 kDa. In the light of the observations and other evidences, a hypothesis was postulated that the SARS-CoV N protein could be phosphorylated in eukaryotes. To locate the plausible regions of phosphorylation in the N protein, two truncated N proteins were generated in E. coli and treated with PKC[alpha]. The two truncated N proteins after incubation of PKC[alpha] exhibited the differently electrophoretic behaviors on 2DE, suggesting that the region of 1-256 aa in the N protein was the possible target for PKC[alpha] phosphorylation. Moreover, the SARS-CoV N protein expressed in yeast were partially digested with trypsin and carefully analyzed by MALDI-TOF/TOF MS. In contrast to the completely tryptic digestion, these partially digested fragments generated two new peptide mass signals with neutral loss, and MS/MS analysis revealed two phosphorylated peptides located at the "dense serine" island in the N protein with amino acid sequences, GFYAEGSRGGSQASSRSSSR and GNSGNSTPGSSRGNSPARMASGGGK. With the PKC[alpha] phosphorylation treatment and the partially tryptic digestion, the N protein expressed in E. coli released the same peptides as observed in yeast cells. Thus, this investigation provided the preliminary data to determine the phosphorylation sites in the SARS-CoV N protein, and

  18. Genomes of Abundant and Widespread Viruses from the Deep Ocean

    Directory of Open Access Journals (Sweden)

    Carolina Megumi Mizuno

    2016-07-01

    Full Text Available The deep sea is a massive, largely oligotrophic ecosystem, stretched over nearly 65% of the planet’s surface. Deep-sea planktonic communities are almost completely dependent upon organic carbon sinking from the productive surface, forming a vital component of global biogeochemical cycles. However, despite their importance, viruses from the deep ocean remain largely unknown. Here, we describe the first complete genomes of deep-sea viruses assembled from metagenomic fosmid libraries. “Candidatus Pelagibacter” (SAR11 phage HTVC010P and Puniceispirillum phage HMO-2011 are considered the most abundant cultured marine viruses known to date. Remarkably, some of the viruses described here recruited as many reads from deep waters as these viruses do in the photic zone, and, considering the gigantic scale of the bathypelagic habitat, these genomes provide information about what could be some of the most abundant viruses in the world at large. Their role in the viral shunt in the global ocean could be very significant. Despite the challenges encountered in inferring the identity of their hosts, we identified one virus predicted to infect members of the globally distributed SAR11 cluster. We also identified a number of putative proviruses from diverse taxa, including deltaproteobacteria, bacteroidetes, SAR11, and gammaproteobacteria. Moreover, our findings also indicate that lysogeny is the preferred mode of existence for deep-sea viruses inhabiting an energy-limited environment, in sharp contrast to the predominantly lytic lifestyle of their photic-zone counterparts. Some of the viruses show a widespread distribution, supporting the tenet “everything is everywhere” for the deep-ocean virome.

  19. Infrastructure monitoring with spaceborne SAR sensors

    CERN Document Server

    ANGHEL, ANDREI; CACOVEANU, REMUS

    2017-01-01

    This book presents a novel non-intrusive infrastructure monitoring technique based on the detection and tracking of scattering centers in spaceborne SAR images. The methodology essentially consists of refocusing each available SAR image on an imposed 3D point cloud associated to the envisaged infrastructure element and identifying the reliable scatterers to be monitored by means of four dimensional (4D) tomography. The methodology described in this book provides a new perspective on infrastructure monitoring with spaceborne SAR images, is based on a standalone processing chain, and brings innovative technical aspects relative to conventional approaches. The book is intended primarily for professionals and researchers working in the area of critical infrastructure monitoring by radar remote sensing.

  20. Identifying the Conditions Under Which Antibodies Protect Against Infection by Equine Infectious Anemia Virus

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    Elissa J. Schwartz

    2014-05-01

    Full Text Available The ability to predict the conditions under which antibodies protect against viral infection would transform our approach to vaccine development. A more complete understanding is needed of antibody protection against lentivirus infection, as well as the role of mutation in resistance to an antibody vaccine. Recently, an example of antibody-mediated vaccine protection has been shown via passive transfer of neutralizing antibodies before equine infectious anemia virus (EIAV infection of horses with severe combined immunodeficiency (SCID. Viral dynamic modeling of antibody protection from EIAV infection in SCID horses may lead to insights into the mechanisms of control of infection by antibody vaccination. In this work, such a model is constructed in conjunction with data from EIAV infection of SCID horses to gain insights into multiple strain competition in the presence of antibody control. Conditions are determined under which wild-type infection is eradicated with the antibody vaccine. In addition, a three-strain competition model is considered in which a second mutant strain may coexist with the first mutant strain. The conditions that permit viral escape by the mutant strains are determined, as are the effects of variation in the model parameters. This work extends the current understanding of competition and antibody control in lentiviral infection, which may provide insights into the development of vaccines that stimulate the immune system to control infection effectively.

  1. Identifying a few foot-and-mouth disease virus signature nucleotide strings for computational genotyping

    Directory of Open Access Journals (Sweden)

    Xu Lizhe

    2008-06-01

    Full Text Available Abstract Background Serotypes of the Foot-and-Mouth disease viruses (FMDVs were generally determined by biological experiments. The computational genotyping is not well studied even with the availability of whole viral genomes, due to uneven evolution among genes as well as frequent genetic recombination. Naively using sequence comparison for genotyping is only able to achieve a limited extent of success. Results We used 129 FMDV strains with known serotype as training strains to select as many as 140 most serotype-specific nucleotide strings. We then constructed a linear-kernel Support Vector Machine classifier using these 140 strings. Under the leave-one-out cross validation scheme, this classifier was able to assign correct serotype to 127 of these 129 strains, achieving 98.45% accuracy. It also assigned serotype correctly to an independent test set of 83 other FMDV strains downloaded separately from NCBI GenBank. Conclusion Computational genotyping is much faster and much cheaper than the wet-lab based biological experiments, upon the availability of the detailed molecular sequences. The high accuracy of our proposed method suggests the potential of utilizing a few signature nucleotide strings instead of whole genomes to determine the serotypes of novel FMDV strains.

  2. An Adaptive Ship Detection Scheme for Spaceborne SAR Imagery

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    Xiangguang Leng

    2016-08-01

    Full Text Available With the rapid development of spaceborne synthetic aperture radar (SAR and the increasing need of ship detection, research on adaptive ship detection in spaceborne SAR imagery is of great importance. Focusing on practical problems of ship detection, this paper presents a highly adaptive ship detection scheme for spaceborne SAR imagery. It is able to process a wide range of sensors, imaging modes and resolutions. Two main stages are identified in this paper, namely: ship candidate detection and ship discrimination. Firstly, this paper proposes an adaptive land masking method using ship size and pixel size. Secondly, taking into account the imaging mode, incidence angle, and polarization channel of SAR imagery, it implements adaptive ship candidate detection in spaceborne SAR imagery by applying different strategies to different resolution SAR images. Finally, aiming at different types of typical false alarms, this paper proposes a comprehensive ship discrimination method in spaceborne SAR imagery based on confidence level and complexity analysis. Experimental results based on RADARSAT-1, RADARSAT-2, TerraSAR-X, RS-1, and RS-3 images demonstrate that the adaptive scheme proposed in this paper is able to detect ship targets in a fast, efficient and robust way.

  3. Crop Classification by Polarimetric SAR

    DEFF Research Database (Denmark)

    Skriver, Henning; Svendsen, Morten Thougaard; Nielsen, Flemming

    1999-01-01

    Polarimetric SAR-data of agricultural fields have been acquired by the Danish polarimetric L- and C-band SAR (EMISAR) during a number of missions at the Danish agricultural test site Foulum during 1995. The data are used to study the classification potential of polarimetric SAR data using...... the Wishart distributed covariance matrix. In general, the improvement of using polarimetric SAR data compared to multipolarization SAR data is larger at L-band compared to C-band. On the other hand, the variability due to natural variation and different incidence angles is larger at L-band compared to C-band...

  4. Rapid inactivation of SARS-like coronaviruses.

    Energy Technology Data Exchange (ETDEWEB)

    Kapil, Sanjay (Kansas State University, Manhattan, KS); Oberst, R. D. (Kansas State University, Manhattan, KS); Bieker, Jill Marie; Tucker, Mark David; Souza, Caroline Ann; Williams, Cecelia Victoria

    2004-03-01

    Chemical disinfection and inactivation of viruses is largely understudied, but is very important especially in the case of highly infectious viruses. The purpose of this LDRD was to determine the efficacy of the Sandia National Laboratories developed decontamination formulations against Bovine Coronavirus (BCV) as a surrogate for the coronavirus that causes Severe Acute Respiratory Syndrome (SARS) in humans. The outbreak of SARS in late 2002 resulted from a highly infectious virus that was able to survive and remain infectious for extended periods. For this study, preliminary testing with Escherichia coli MS-2 (MS-2) and Escherichia coli T4 (T4) bacteriophages was conducted to develop virucidal methodology for verifying the inactivation after treatment with the test formulations following AOAC germicidal methodologies. After the determination of various experimental parameters (i.e. exposure, concentration) of the formulations, final testing was conducted on BCV. All experiments were conducted with various organic challenges (horse serum, bovine feces, compost) for results that more accurately represent field use condition. The MS-2 and T4 were slightly more resistant than BCV and required a 2 minute exposure while BCV was completely inactivated after a 1 minute exposure. These results were also consistent for the testing conducted in the presence of the various organic challenges indicating that the test formulations are highly effective for real world application.

  5. Bistatic SAR: Proof of Concept.

    Energy Technology Data Exchange (ETDEWEB)

    Yocky, David A.; Doren, Neall E.; Bacon, Terry A.; Wahl, Daniel E.; Eichel, Paul H.; Jakowatz, Charles V,; Delaplain, Gilbert G.; Dubbert, Dale F.; Tise, Bertice L.; White, Kyle R.

    2014-10-01

    Typical synthetic aperture RADAR (SAR) imaging employs a co-located RADAR transmitter and receiver. Bistatic SAR imaging separates the transmitter and receiver locations. A bistatic SAR configuration allows for the transmitter and receiver(s) to be in a variety of geometric alignments. Sandia National Laboratories (SNL) / New Mexico proposed the deployment of a ground-based RADAR receiver. This RADAR receiver was coupled with the capability of digitizing and recording the signal collected. SNL proposed the possibility of creating an image of targets the illuminating SAR observes. This document describes the developed hardware, software, bistatic SAR configuration, and its deployment to test the concept of a ground-based bistatic SAR. In the proof-of-concept experiments herein, the RADAR transmitter will be a commercial SAR satellite and the RADAR receiver will be deployed at ground level, observing and capturing RADAR ground/targets illuminated by the satellite system.

  6. SARS-like WIV1-CoV poised for human emergence

    Science.gov (United States)

    Menachery, Vineet D.; Yount, Boyd L.; Sims, Amy C.; Debbink, Kari; Agnihothram, Sudhakar S.; Gralinski, Lisa E.; Graham, Rachel L.; Scobey, Trevor; Plante, Jessica A.; Royal, Scott R.; Swanstrom, Jesica; Sheahan, Timothy P.; Pickles, Raymond J.; Corti, Davide; Randell, Scott H.; Lanzavecchia, Antonio; Marasco, Wayne A.; Baric, Ralph S.

    2016-01-01

    Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations. PMID:26976607

  7. Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

    Directory of Open Access Journals (Sweden)

    Bin Zhou

    2014-10-01

    Full Text Available Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV. Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1. This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2 showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

  8. RNAseq expression analysis of resistant and susceptible mice after influenza A virus infection identifies novel genes associated with virus replication and important for host resistance to infection.

    Science.gov (United States)

    Wilk, Esther; Pandey, Ashutosh K; Leist, Sarah Rebecca; Hatesuer, Bastian; Preusse, Matthias; Pommerenke, Claudia; Wang, Junxi; Schughart, Klaus

    2015-09-02

    The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suited to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilized a dual RNAseq approach that allowed us to investigate both viral and host gene expression in the same individual mouse after H1N1 infection. We performed a detailed expression analysis to identify (i) correlations between changes in expression of host and virus genes, (ii) host genes involved in viral replication, and (iii) genes showing differential expression between two mouse strains that strongly differ in resistance to influenza infections. These genes may be key players involved in regulating the differences in pathogenesis and host defense mechanisms after influenza A infections. Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional viral load measurements. Furthermore, we investigated the functional role of two genes, Reg3g and Irf7, in knock-out mice and found that deletion of the Irf7 gene renders the host highly susceptible to H1N1 infection. Using RNAseq analysis we identified novel genes important for viral replication or the host defense. This study adds further important knowledge to host-pathogen-interactions and suggests additional candidates that are crucial for host susceptibility or survival during influenza A infections.

  9. Viruses and interactomes in translation.

    Science.gov (United States)

    Meyniel-Schicklin, Laurène; de Chassey, Benoît; André, Patrice; Lotteau, Vincent

    2012-07-01

    A decade of high-throughput screenings for intraviral and virus-host protein-protein interactions led to the accumulation of data and to the development of theories on laws governing interactome organization for many viruses. We present here a computational analysis of intraviral protein networks (EBV, FLUAV, HCV, HSV-1, KSHV, SARS-CoV, VACV, and VZV) and virus-host protein networks (DENV, EBV, FLUAV, HCV, and VACV) from up-to-date interaction data, using various mathematical approaches. If intraviral networks seem to behave similarly, they are clearly different from the human interactome. Viral proteins target highly central human proteins, which are precisely the Achilles' heel of the human interactome. The intrinsic structural disorder is a distinctive feature of viral hubs in virus-host interactomes. Overlaps between virus-host data sets identify a core of human proteins involved in the cellular response to viral infection and in the viral capacity to hijack the cell machinery for viral replication. Host proteins that are strongly targeted by a virus seem to be particularly attractive for other viruses. Such protein-protein interaction networks and their analysis represent a powerful resource from a therapeutic perspective.

  10. Redescriptions of six species of Ilyodromus Sars, 1894 (Crustacea, Ostracoda, Cyprididae) from New Zealand and Eastern Australia.

    Science.gov (United States)

    Shearn, Rylan; Halse, Stuart; Koenders, Annette; Schön, Isa; Martens, Koen

    2014-10-23

    In this paper, we redescribe six species of the genus Ilyodromus Sars, 1894: I, stanleyanus (King, 1855), I. varrovillius (King, 1855), I. smaragdinus Sars, 1894, I. obtusus Sars, 1894, I. substriatus Sars, 1894 and I. viridulus (Brady, 1886) using materials stored in the Oslo museum (Norway) and (re-) described by G.O. Sars.  For each species examined, we have identified a number of additional diagnostic characters to those used by Sars and earlier authors. In particular, the length of setae, claws and segments of the antennule, antenna, sixth limb, and caudal ramus appear to be important for species delineation in the genus, as does the internal structure of the valves.

  11. Phosphatidylcholine Alteration Identified Using MALDI Imaging MS in HBV-Infected Mouse Livers and Virus-Mediated Regeneration Defects

    Science.gov (United States)

    Park, Eun-Sook; Lee, Jeong Hwa; Hong, Ji Hye; Park, Yong Kwang; Lee, Joon Won; Lee, Won-Jae; Lee, Jae Won; Kim, Kwang Pyo; Kim, Kyun-Hwan

    2014-01-01

    In this study, we investigated whether hepatitis B virus (HBV) causes the alteration of lipid metabolism and composition during acute infection and liver regeneration in a mouse model. The liver controls lipid biogenesis and bile acid homeostasis. Infection of HBV causes various liver diseases and impairs liver regeneration. As there are very few reports available in the literature on lipid alterations by HBV infection or HBV-mediated liver injury, we have analyzed phospholipids that have important roles in liver regeneration by using matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) in the livers of HBV model mice. As a result, we identified different phosphatidylcholines (PCs) showing significant changes in their composition as well as cationized ion adduct formation in HBV-infected mouse livers which are associated with virus-mediated regeneration defects. To find the factor of altered PCs, the expression kinetics of enzymes was also examined that regulate PC biosynthesis during liver regeneration. It is noteworthy that the expression of choline-phosphate cytidylyltransferase A (PCYT1A) was significantly delayed in wild type HBV-expressing livers. Moreover, the amount of hepatic total PC was also significantly decreased in wt HBV-expressing mice. These results suggest that infection of HBV alters the composition of PCs which may involve in HBV-mediated regeneration defects and liver disease. PMID:25101682

  12. De novo transcriptome sequencing in Frankliniella occidentalis to identify genes involved in plant virus transmission and insecticide resistance.

    Science.gov (United States)

    Zhang, Zhijun; Zhang, Pengjun; Li, Weidi; Zhang, Jinming; Huang, Fang; Yang, Jian; Bei, Yawei; Lu, Yaobin

    2013-05-01

    The western flower thrips (WFT), Frankliniella occidentalis, a world-wide invasive insect, causes agricultural damage by directly feeding and by indirectly vectoring Tospoviruses, such as Tomato spotted wilt virus (TSWV). We characterized the transcriptome of WFT and analyzed global gene expression of WFT response to TSWV infection using Illumina sequencing platform. We compiled 59,932 unigenes, and identified 36,339 unigenes by similarity analysis against public databases, most of which were annotated using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Within these annotated transcripts, we collected 278 sequences related to insecticide resistance. GO and KEGG analysis of different expression genes between TSWV-infected and non-infected WFT population revealed that TSWV can regulate cellular process and immune response, which might lead to low virus titers in thrips cells and no detrimental effects on F. occidentalis. This data-set not only enriches genomic resource for WFT, but also benefits research into its molecular genetics and functional genomics. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Mumps Virus: Modification of the Identify-Isolate-Inform Tool for Frontline Healthcare Providers

    OpenAIRE

    Koenig, Kristi L.; Shastry, Siri; Mzahim, Bandr; Almadhyan, Abdulmajeed; Burns, Michael J.

    2016-01-01

    Mumps is a highly contagious viral infection that became rare in most industrialized countriesfollowing the introduction of measles-mumps-rubella (MMR) vaccine in 1967. The disease, however,has been re-emerging with several outbreaks over the past decade. Many clinicians have neverseen a case of mumps. To assist frontline healthcare providers with detecting potential casesand initiating critical actions, investigators modified the “Identify-Isolate-Inform” tool for mumpsinfection. The tool is...

  14. Bistatic sAR data processing algorithms

    CERN Document Server

    Qiu, Xiaolan; Hu, Donghui

    2013-01-01

    Synthetic Aperture Radar (SAR) is critical for remote sensing. It works day and night, in good weather or bad. Bistatic SAR is a new kind of SAR system, where the transmitter and receiver are placed on two separate platforms. Bistatic SAR is one of the most important trends in SAR development, as the technology renders SAR more flexible and safer when used in military environments. Imaging is one of the most difficult and important aspects of bistatic SAR data processing. Although traditional SAR signal processing is fully developed, bistatic SAR has a more complex system structure, so sign

  15. Small Molecule Inhibitors of the LEDGF Site of Human Immunodeficiency Virus Integrase Identified by Fragment Screening and Structure Based Design

    Science.gov (United States)

    Peat, Thomas S.; Rhodes, David I.; Vandegraaff, Nick; Le, Giang; Smith, Jessica A.; Clark, Lisa J.; Jones, Eric D.; Coates, Jonathan A. V.; Thienthong, Neeranat; Newman, Janet; Dolezal, Olan; Mulder, Roger; Ryan, John H.; Savage, G. Paul; Francis, Craig L.; Deadman, John J.

    2012-01-01

    A fragment-based screen against human immunodeficiency virus type 1 (HIV) integrase led to a number of compounds that bound to the lens epithelium derived growth factor (LEDGF) binding site of the integrase catalytic core domain. We determined the crystallographic structures of complexes of the HIV integrase catalytic core domain for 10 of these compounds and quantitated the binding by surface plasmon resonance. We demonstrate that the compounds inhibit the interaction of LEDGF with HIV integrase in a proximity AlphaScreen assay, an assay for the LEDGF enhancement of HIV integrase strand transfer and in a cell based assay. The compounds identified represent a potential framework for the development of a new series of HIV integrase inhibitors that do not bind to the catalytic site of the enzyme. PMID:22808106

  16. Small molecule inhibitors of the LEDGF site of human immunodeficiency virus integrase identified by fragment screening and structure based design.

    Directory of Open Access Journals (Sweden)

    Thomas S Peat

    Full Text Available A fragment-based screen against human immunodeficiency virus type 1 (HIV integrase led to a number of compounds that bound to the lens epithelium derived growth factor (LEDGF binding site of the integrase catalytic core domain. We determined the crystallographic structures of complexes of the HIV integrase catalytic core domain for 10 of these compounds and quantitated the binding by surface plasmon resonance. We demonstrate that the compounds inhibit the interaction of LEDGF with HIV integrase in a proximity AlphaScreen assay, an assay for the LEDGF enhancement of HIV integrase strand transfer and in a cell based assay. The compounds identified represent a potential framework for the development of a new series of HIV integrase inhibitors that do not bind to the catalytic site of the enzyme.

  17. Accessory proteins of SARS-CoV and other coronaviruses.

    Science.gov (United States)

    Liu, Ding Xiang; Fung, To Sing; Chong, Kelvin Kian-Long; Shukla, Aditi; Hilgenfeld, Rolf

    2014-09-01

    The huge RNA genome of SARS coronavirus comprises a number of open reading frames that code for a total of eight accessory proteins. Although none of these are essential for virus replication, some appear to have a role in virus pathogenesis. Notably, some SARS-CoV accessory proteins have been shown to modulate the interferon signaling pathways and the production of pro-inflammatory cytokines. The structural information on these proteins is also limited, with only two (p7a and p9b) having their structures determined by X-ray crystallography. This review makes an attempt to summarize the published knowledge on SARS-CoV accessory proteins, with an emphasis on their involvement in virus-host interaction. The accessory proteins of other coronaviruses are also briefly discussed. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses" (see Introduction by Hilgenfeld and Peiris (2013)). Copyright © 2014 Elsevier B.V. All rights reserved.

  18. SARS-CoV Infection in a Restaurant from Palm Civet

    Science.gov (United States)

    Wang, Ming; Yan, Meiying; Xu, Huifang; Liang, Weili; Kan, Biao; Zheng, Bojian; Chen, Honglin; Zheng, Han; Xu, Yanmei; Zhang, Enmin; Wang, Hongxia; Ye, Jingrong; Li, Guichang; Li, Machao; Cui, Zhigang; Liu, Yu-Fei; Guo, Rong-Tong; Liu, Xiao-Ning; Zhan, Liu-Hua; Zhou, Duan-Hua; Zhao, Ailan; Hai, Rong; Yu, Dongzhen; Guan, Yi

    2005-01-01

    Epidemiologic investigations showed that 2 of 4 patients with severe acute respiratory syndrome (SARS) identified in the winter of 2003–2004 were a waitress at a restaurant in Guangzhou, China, that served palm civets as food and a customer who ate in the restaurant a short distance from animal cages. All 6 palm civets at the restaurant were positive for SARS-associated coronavirus (SARS-CoV). Partial spike (S) gene sequences of SARS-CoV from the 2 patients were identical to 4 of 5 S gene viral sequences from palm civets. Phylogenetic analysis showed that SARS-CoV from palm civets in the restaurant was most closely related to animal isolates. SARS cases at the restaurant were the result of recent interspecies transfer from the putative palm civet reservoir, and not the result of continued circulation of SARS-CoV in the human population. PMID:16485471

  19. SAR++: A Multi-Channel Scalable and Reconfigurable SAR System

    DEFF Research Database (Denmark)

    Høeg, Flemming; Christensen, Erik Lintz

    2002-01-01

    SAR++ is a technology program aiming at developing know-how and technology needed to design the next generation civilian SAR systems. Technology has reached a state, which allows major parts of the digital subsystem to be built using custom-off-the-shelf (COTS) components. A design goal...... is to design a modular, scalable and reconfigurable SAR system using such components, in order to ensure maximum flexibility for the users of the actual system and for future system updates. Having these aspects in mind the SAR++ system is presented with focus on the digital subsystem architecture...

  20. VIRUSES

    Indian Academy of Sciences (India)

    and-mouth disease in livestock was an infectious particle smaller than any bacteria. This was the first clue to the nature of viruses, genetic entities that lie somewhere in the gray area between living and non-living states.

  1. Validation of case-finding algorithms derived from administrative data for identifying adults living with human immunodeficiency virus infection.

    Directory of Open Access Journals (Sweden)

    Tony Antoniou

    Full Text Available OBJECTIVE: We sought to validate a case-finding algorithm for human immunodeficiency virus (HIV infection using administrative health databases in Ontario, Canada. METHODS: We constructed 48 case-finding algorithms using combinations of physician billing claims, hospital and emergency room separations and prescription drug claims. We determined the test characteristics of each algorithm over various time frames for identifying HIV infection, using data abstracted from the charts of 2,040 randomly selected patients receiving care at two medical practices in Toronto, Ontario as the reference standard. RESULTS: With the exception of algorithms using only a single physician claim, the specificity of all algorithms exceeded 99%. An algorithm consisting of three physician claims over a three year period had a sensitivity and specificity of 96.2% (95% CI 95.2%-97.9% and 99.6% (95% CI 99.1%-99.8%, respectively. Application of the algorithm to the province of Ontario identified 12,179 HIV-infected patients in care for the period spanning April 1, 2007 to March 31, 2009. CONCLUSIONS: Case-finding algorithms generated from administrative data can accurately identify adults living with HIV. A relatively simple "3 claims in 3 years" definition can be used for assembling a population-based cohort and facilitating future research examining trends in health service use and outcomes among HIV-infected adults in Ontario.

  2. Novel inhibitors targeting Venezuelan equine encephalitis virus capsid protein identified using In Silico Structure-Based-Drug-Design.

    Science.gov (United States)

    Shechter, Sharon; Thomas, David R; Lundberg, Lindsay; Pinkham, Chelsea; Lin, Shih-Chao; Wagstaff, Kylie M; Debono, Aaron; Kehn-Hall, Kylene; Jans, David A

    2017-12-18

    Therapeutics are currently unavailable for Venezuelan equine encephalitis virus (VEEV), which elicits flu-like symptoms and encephalitis in humans, with an estimated 14% of cases resulting in neurological disease. Here we identify anti-VEEV agents using in silico structure-based-drug-design (SBDD) for the first time, characterising inhibitors that block recognition of VEEV capsid protein (C) by the host importin (IMP) α/β1 nuclear transport proteins. From an initial screen of 1.5 million compounds, followed by in silico refinement and screening for biological activity in vitro, we identified 21 hit compounds which inhibited IMPα/β1:C binding with IC50s as low as 5 µM. Four compounds were found to inhibit nuclear import of C in transfected cells, with one able to reduce VEEV replication at µM concentration, concomitant with reduced C nuclear accumulation in infected cells. Further, this compound was inactive against a mutant VEEV that lacks high affinity IMPα/β1:C interaction, supporting the mode of its antiviral action to be through inhibiting C nuclear localization. This successful application of SBDD paves the way for lead optimization for VEEV antivirals, and is an exciting prospect to identify inhibitors for the many other viral pathogens of significance that require IMPα/β1 in their infectious cycle.

  3. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    NARCIS (Netherlands)

    A. de Lang (Anna); T. Baas (Tracey); T.H. Teal (Thomas); L.M.E. Leijten (Lonneke); B. Rain (Brandon); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); M.G. Katze (Michael)

    2007-01-01

    textabstractThe pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs

  4. Circular SAR GMTI

    Science.gov (United States)

    Page, Douglas; Owirka, Gregory; Nichols, Howard; Scarborough, Steven

    2014-06-01

    We describe techniques for improving ground moving target indication (GMTI) performance in multi-channel synthetic aperture radar (SAR) systems. Our approach employs a combination of moving reference processing (MRP) to compensate for defocus of moving target SAR responses and space-time adaptive processing (STAP) to mitigate the effects of strong clutter interference. Using simulated moving target and clutter returns, we demonstrate focusing of the target return using MRP, and discuss the effect of MRP on the clutter response. We also describe formation of adaptive degrees of freedom (DOFs) for STAP filtering of MRP processed data. For the simulated moving target in clutter example, we demonstrate improvement in the signal to interference plus noise (SINR) loss compared to more standard algorithm configurations. In addition to MRP and STAP, the use of tracker feedback, false alarm mitigation, and parameter estimation techniques are also described. A change detection approach for reducing false alarms from clutter discretes is outlined, and processing of a measured data coherent processing interval (CPI) from a continuously orbiting platform is described. The results demonstrate detection and geolocation of a high-value target under track. The endoclutter target is not clearly visible in single-channel SAR chips centered on the GMTI track prediction. Detections are compared to truth data before and after geolocation using measured angle of arrival (AOA).

  5. MISSEL: a method to identify a large number of small species-specific genomic subsequences and its application to viruses classification.

    Science.gov (United States)

    Fiscon, Giulia; Weitschek, Emanuel; Cella, Eleonora; Lo Presti, Alessandra; Giovanetti, Marta; Babakir-Mina, Muhammed; Ciotti, Marco; Ciccozzi, Massimo; Pierangeli, Alessandra; Bertolazzi, Paola; Felici, Giovanni

    2016-01-01

    Continuous improvements in next generation sequencing technologies led to ever-increasing collections of genomic sequences, which have not been easily characterized by biologists, and whose analysis requires huge computational effort. The classification of species emerged as one of the main applications of DNA analysis and has been addressed with several approaches, e.g., multiple alignments-, phylogenetic trees-, statistical- and character-based methods. We propose a supervised method based on a genetic algorithm to identify small genomic subsequences that discriminate among different species. The method identifies multiple subsequences of bounded length with the same information power in a given genomic region. The algorithm has been successfully evaluated through its integration into a rule-based classification framework and applied to three different biological data sets: Influenza, Polyoma, and Rhino virus sequences. We discover a large number of small subsequences that can be used to identify each virus type with high accuracy and low computational time, and moreover help to characterize different genomic regions. Bounding their length to 20, our method found 1164 characterizing subsequences for all the Influenza virus subtypes, 194 for all the Polyoma viruses, and 11 for Rhino viruses. The abundance of small separating subsequences extracted for each genomic region may be an important support for quick and robust virus identification. Finally, useful biological information can be derived by the relative location and abundance of such subsequences along the different regions.

  6. Mumps Virus: Modification of the Identify-Isolate-Inform Tool for Frontline Healthcare Providers.

    Science.gov (United States)

    Koenig, Kristi L; Shastry, Siri; Mzahim, Bandr; Almadhyan, Abdulmajeed; Burns, Michael J

    2016-09-01

    Mumps is a highly contagious viral infection that became rare in most industrialized countries following the introduction of measles-mumps-rubella (MMR) vaccine in 1967. The disease, however, has been re-emerging with several outbreaks over the past decade. Many clinicians have never seen a case of mumps. To assist frontline healthcare providers with detecting potential cases and initiating critical actions, investigators modified the "Identify-Isolate-Inform" tool for mumps infection. The tool is applicable to regions with rare incidences or local outbreaks, especially seen in college students, as well as globally in areas where vaccination is less common. Mumps begins with a prodrome of low-grade fever, myalgias and malaise/anorexia, followed by development of nonsuppurative parotitis, which is the pathognomonic finding associated with acute mumps infection. Orchitis and meningitis are the two most common serious complications, with hearing loss and infertility occurring rarely. Providers should consider mumps in patients with exposure to a known case or international travel to endemic regions who present with consistent signs and symptoms. If mumps is suspected, healthcare providers must immediately implement standard and droplet precautions and notify the local health department and hospital infection control personnel.

  7. Mumps Virus: Modification of the Identify-Isolate-Inform Tool for Frontline Healthcare Providers

    Directory of Open Access Journals (Sweden)

    Kristi L. Koenig

    2016-09-01

    Full Text Available Mumps is a highly contagious viral infection that became rare in most industrialized countries following the introduction of measles-mumps-rubella (MMR vaccine in 1967. The disease, however, has been re-emerging with several outbreaks over the past decade. Many clinicians have never seen a case of mumps. To assist frontline healthcare providers with detecting potential cases and initiating critical actions, investigators modified the “Identify-Isolate-Inform” tool for mumps infection. The tool is applicable to regions with rare incidences or local outbreaks, especially seen in college students, as well as globally in areas where vaccination is less common. Mumps begins with a prodrome of low-grade fever, myalgias and malaise/anorexia, followed by development of nonsuppurative parotitis, which is the pathognomonic finding associated with acute mumps infection. Orchitis and meningitis are the two most common serious complications, with hearing loss and infertility occurring rarely. Providers should consider mumps in patients with exposure to a known case or international travel to endemic regions who present with consistent signs and symptoms. If mumps is suspected, healthcare providers must immediately implement standard and droplet precautions and notify the local health department and hospital infection control personnel.

  8. Wetland InSAR

    Science.gov (United States)

    Wdowinski, S.; Kim, S.; Amelung, F.; Dixon, T.

    2006-12-01

    Wetlands are transition zones where the flow of water, the nutrient cycling, and the sun energy meet to produce a unique and very productive ecosystem. They provide critical habitat for a wide variety of plant and animal species, including the larval stages of many ocean fish. Wetlands also have a valuable economical importance, as they filter nutrients and pollutants from fresh water used by human and provide aquatic habitats for outdoor recreation, tourism, and fishing. Globally, many such regions are under severe environmental stress, mainly from urban development, pollution, and rising sea level. However, there is increasing recognition of the importance of these habitats, and mitigation and restoration activities have begun in a few regions. A key element in wetlands conservation, management, and restoration involves monitoring its hydrologic system, as the entire ecosystem depends on its water supply. Heretofore, hydrologic monitoring of wetlands are conducted by stage (water level) stations, which provide good temporal resolution, but suffer from poor spatial resolution, as stage station are typically distributed several, or even tens of kilometers, from one another. Wetland application of InSAR provides the needed high spatial resolution hydrological observations, complementing the high temporal resolution terrestrial observations. Although conventional wisdom suggests that interferometry does not work in vegetated areas, several studies have shown that both L- and C-band interferograms with short acquisition intervals (1-105 days) can maintain excellent coherence over wetlands. In this study we explore the usage of InSAR for detecting water level changes in various wetland environments around the world, including the Everglades (south Florida), Louisiana Coast (southern US), Chesapeake Bay (eastern US), Pantanal (Brazil), Okavango Delta (Botswana), and Lena Delta (Siberia). Our main study area is the Everglades wetland (south Florida), which is covered by

  9. Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine.

    Science.gov (United States)

    Kapadia, Sagar U; Rose, John K; Lamirande, Elaine; Vogel, Leatrice; Subbarao, Kanta; Roberts, Anjeanette

    2005-09-30

    Although the recent SARS coronavirus (SARS-CoV) that appeared in 2002 has now been contained, the possibility of re-emergence of SARS-CoV remains. Due to the threat of re-emergence, the overall fatality rate of approximately 10%, and the rapid dispersion of the virus via international travel, viable vaccine candidates providing protection from SARS are clearly needed. We developed an attenuated VSV recombinant (VSV-S) expressing the SARS coronavirus (SARS-CoV) spike (S) protein. In cells infected with this recombinant, S protein was synthesized, glycosylated at approximately 17 Asn residues, and transported via the Golgi to the cell surface. Mice vaccinated with VSV-S developed SARS-neutralizing antibody and were able to control a challenge with SARS-CoV performed at 1 month or 4 months after a single vaccination. We also demonstrated, by passive antibody transfer, that the antibody response induced by the vaccine was sufficient for controlling SARS-CoV infection. A VSV-vectored SARS vaccine could have significant advantages over other SARS vaccine candidates described to date.

  10. Novel Polarimetric SAR Interferometry Algorithms Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Polarimetric SAR interferometry (PolInSAR) is a recently developed synthetic aperture radar (SAR) imaging mode that combines the capabilities of radar polarimetry...

  11. Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003

    Directory of Open Access Journals (Sweden)

    Ooi Eng

    2004-09-01

    Full Text Available Abstract Background The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations. Methods We sequenced complete SARS-CoV genomes taken from primary human tissues (SIN3408, SIN3725V, SIN3765V, cultured isolates (SIN848, SIN846, SIN842, SIN845, SIN847, SIN849, SIN850, SIN852, SIN3408L, and five consecutive Vero cell passages (SIN2774_P1, SIN2774_P2, SIN2774_P3, SIN2774_P4, SIN2774_P5 arising from SIN2774 isolate. These represented individual patient samples, serial in vitro passages in cell culture, and paired human and cell culture isolates. Employing a refined mutation filtering scheme and constant mutation rate model, the mutation rates were estimated and the possible date of emergence was calculated. Phylogenetic analysis was used to uncover molecular relationships between the isolates. Results Close examination of whole genome sequence of 54 SARS-CoV isolates identified before 14th October 2003, including 22 from patients in Singapore, revealed the mutations engendered during human-to-Vero and Vero-to-human transmission as well as in multiple Vero cell passages in order to refine our analysis of human-to-human transmission. Though co-infection by different quasipecies in individual tissue samples is observed, the in vitro mutation rate of the SARS-CoV in Vero cell passage is negligible. The in vivo mutation rate, however, is consistent with estimates of other RNA viruses at approximately 5.7 × 10-6 nucleotide substitutions per site per day (0.17 mutations per genome per day, or two mutations per human passage (adjusted R-square = 0.4014. Using the immediate Hotel M contact isolates as roots, we observed that the SARS epidemic has generated four major genetic groups that are

  12. Identifying protein biomarkers in predicting disease severity of dengue virus infection using immune-related protein microarray.

    Science.gov (United States)

    Soe, Hui Jen; Yong, Yean K; Al-Obaidi, Mazen M Jamil; Raju, Chandramathi Samudi; Gudimella, Ranganath; Manikam, Rishya; Sekaran, Shamala Devi

    2018-02-01

    Dengue virus is one of the most widespread flaviviruses that re-emerged throughout recent decades. The progression from mild dengue to severe dengue (SD) with the complications such as vascular leakage and hemorrhage increases the fatality rate of dengue. The pathophysiology of SD is not entirely clear. To investigate potential biomarkers that are suggestive of pathogenesis of SD, a small panel of serum samples selected from 1 healthy individual, 2 dengue patients without warning signs (DWS-), 2 dengue patients with warning signs (DWS+), and 5 patients with SD were subjected to a pilot analysis using Sengenics Immunome protein array. The overall fold changes of protein expressions and clustering heat map revealed that PFKFB4, TPM1, PDCL3, and PTPN20A were elevated among patients with SD. Differential expression analysis identified that 29 proteins were differentially elevated greater than 2-fold in SD groups than DWS- and DWS+. From the 29 candidate proteins, pathways enrichment analysis also identified insulin signaling and cytoskeleton pathways were involved in SD, suggesting that the insulin pathway may play a pivotal role in the pathogenesis of SD.

  13. Interactive Web Based Visualization of PS-InSAR and TomoSAR Results

    Science.gov (United States)

    Li, Shanshan; Wei, Lianhuan; Balz, Timo; Liao, Mingsheng

    2013-01-01

    Interactive web based visualization has become an important trend for displaying information dynamically. Synthetic Aperture Radar (SAR) data can be used to measure height and deformation information using interferometric SAR (InSAR) and differential InSAR (D-InSAR). Precise deformation information can be acquired in urban areas using Persistent Scatterer Interferometry (PS-InSAR) and differential SAR tomography (D-TomoSAR). PS-InSAR and TomoSAR results are usually represented as point clouds. In order to visualize this data dynamically, we developed an interactive web-based visualization system.

  14. Interactive Web-Based Visualization of PS-InSAR and TomoSAR

    Science.gov (United States)

    Li, Shanshan; Wei, Lianhuan; Balz, Timo; Liao, Mingsheng

    2013-01-01

    Interactive web based visualization has become an important trend for displaying information dynamically. Synthetic Aperture Radar (SAR) data can be used to measure height and deformation information using interferometric SAR (InSAR) and differential InSAR (D-InSAR). Precise deformation information can be acquired in urban areas using Persistent Scatterer Interferometry (PS-InSAR) and differential SAR tomography (D-TomoSAR). PS-InSAR and TomoSAR results are usually represented as point clouds. In order to visualize this data dynamically, we developed an interactive web-based visualization system

  15. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques

    National Research Council Canada - National Science Library

    Lang, Anna; Baas, Tracey; Teal, Thomas; Leijten, Lonneke; Rain, Brandon; Osterhaus, Albert; Haagmans, Bart; Katze, Michael

    2007-01-01

    textabstractThe pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity...

  16. Multiple viral infections in Agaricus bisporus - Characterisation of 18 unique RNA viruses and 8 ORFans identified by deep sequencing

    OpenAIRE

    Deakin, Gregory; Dobbs, Edward; Julie M. Bennett; Ian M Jones; Grogan, Helen M.; Burton, Kerry S.

    2017-01-01

    Thirty unique non-host RNAs were sequenced in the cultivated fungus, Agaricus bisporus, comprising 18 viruses each encoding an RdRp domain with an additional 8 ORFans (non-host RNAs with no similarity to known sequences). Two viruses were multipartite with component RNAs showing correlative abundances and common 3′ motifs. The viruses, all positive sense single-stranded, were classified into diverse orders/families. Multiple infections of Agaricus may represent a diverse, dynamic and interact...

  17. The use of pyrosequencer-generated sequence-signatures to identify the influenza B-lineage and the subclade of the B/Yamataga-lineage viruses from currently circulating human influenza B viruses.

    Science.gov (United States)

    Deng, Yi-Mo; Iannello, Pina; Caldwell, Natalie; Jelley, Lauren; Komadina, Naomi; Baas, Chantal; Kelso, Anne; Barr, Ian G

    2013-09-01

    Influenza B viruses belong to two antigenically and genetically distinct lineages which co-circulate in varying proportions in many countries. To develop simple, rapid, accurate and robust methods to detect and differentiate currently circulating B-lineage viruses in respiratory samples and virus isolates. Haemagglutinin (HA) gene sequences from more than 6300 influenza B strains were analysed to identify signature sequences that could be used to distinguish between B-lineages and sublineages. Pyrosequencing and a real time PCR assays were developed to detect the major B-lineages (B/Victoria/2/87 or B/Yamagata/16/88) and pyrosequencing for a unique mutation was used to further differentiate the B/Yamagata viruses into two currently co-circulating subgroups. More than 300 influenza virus-containing samples, including original specimens, cell and egg grown viruses, were tested with a 100% accuracy. Furthermore, when the same PCR primers were used in an rRT-PCR assay, the two lineages could be differentiated by their distinct ranges of melting temperature with an overall accuracy of 99% for 158 samples tested. These new pyrosequencing and rRT-PCR methods have the potential to aid the rapid identification of influenza B-lineages for surveillance purposes and to increase the available data for bi-annual selection of viruses for updating influenza vaccines. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Recovering Seasat SAR Data

    Science.gov (United States)

    Logan, T. A.; Arko, S. A.; Rosen, P. A.

    2013-12-01

    To demonstrate the feasibility of orbital remote sensing for global ocean observations, NASA launched Seasat on June 27th, 1978. Being the first space borne SAR mission, Seasat produced the most detailed SAR images of Earth from space ever seen to that point in time. While much of the data collected in the USA was processed optically, a mere 150 scenes had been digitally processed by March 1980. In fact, only an estimated 3% of Seasat data was ever digitally processed. Thus, for over three decades, the majority of the SAR data from this historic mission has been dormant, virtually unavailable to scientists in the 21st century. Over the last year, researchers at the Alaska Satellite Facility (ASF) Distributed Active Archive Center (DAAC) have processed the Seasat SAR archives into imagery products. A telemetry decoding system was created and the data were filtered into readily processable signal files. Due to nearly 35 years of bit rot, the bit error rate (BER) for the ASF DAAC Seasat archives was on the order of 1 out of 100 to 1 out of 100,000. This extremely high BER initially seemed to make much of the data undecodable - because the minor frame numbers are just 7 bits and no range line numbers exist in the telemetry even the 'simple' tasks of tracking the minor frame number or locating the start of each range line proved difficult. Eventually, using 5 frame numbers in sequence and a handful of heuristics, the data were successfully decoded into full range lines. Concurrently, all metadata were stored into external files. Recovery of this metadata was also problematic, the BER making the information highly suspect and, initially at least, unusable in any sort of automated fashion. Because of the BER, all of the single bit metadata fields proved unreliable. Even fields that should be constant for a data take (e.g. receiving station, day of the year) showed high variability, each requiring a median filter to be usable. The most challenging, however, were the

  19. SAR Simulations & Safety.

    Science.gov (United States)

    Fiedler, Thomas M; Ladd, Mark E; Bitz, Andreas K

    2017-03-20

    At ultra-high fields, the assessment of radiofrequency (RF) safety presents several new challenges compared to low-field systems. Multi-channel RF transmit coils in combination with parallel transmit techniques produce time-dependent and spatially varying power loss densities in the tissue. Further, in ultra-high-field systems, localized field effects can be more pronounced due to a transition from the quasi stationary to the electromagnetic field regime. Consequently, local information on the RF field is required for reliable RF safety assessment as well as for monitoring of RF exposure during MR examinations. Numerical RF and thermal simulations for realistic exposure scenarios with anatomical body models are currently the only practical way to obtain the requisite local information on magnetic and electric field distributions as well as tissue temperature. In this article, safety regulations and the fundamental characteristics of RF field distributions in ultra-high-field systems are reviewed. Numerical methods for computation of RF fields as well as typical requirements for the analysis of realistic multi-channel RF exposure scenarios including anatomical body models are highlighted. In recent years, computation of the local tissue temperature has become of increasing interest, since a more accurate safety assessment is expected because temperature is directly related to tissue damage. Regarding thermal simulation, bio-heat transfer models and approaches for taking into account the physiological response of the human body to RF exposure are discussed. In addition, suitable methods are presented to validate calculated RF and thermal results with measurements. Finally, the concept of generalized simulation-based specific absorption rate (SAR) matrix models is discussed. These models can be incorporated into local SAR monitoring in multi-channel MR systems and allow the design of RF pulses under constraints for local SAR. Copyright © 2017 Elsevier Inc. All rights

  20. Genome-Wide Association Study Identifies Risk Variants for Lichen Planus in Patients With Hepatitis C Virus Infection.

    Science.gov (United States)

    Nagao, Yumiko; Nishida, Nao; Toyo-Oka, Licht; Kawaguchi, Atsushi; Amoroso, Antonio; Carrozzo, Marco; Sata, Michio; Mizokami, Masashi; Tokunaga, Katsushi; Tanaka, Yasuhito

    2017-06-01

    There is a close relationship between hepatitis C virus (HCV) infection and lichen planus, a chronic inflammatory mucocutaneous disease. We performed a genome-wide association study (GWAS) to identify genetic variants associated with HCV-related lichen planus. We conducted a GWAS of 261 patients with HCV infection treated at a tertiary medical center in Japan from October 2007 through January 2013; a total of 71 had lichen planus and 190 had normal oral mucosa. We validated our findings in a GWAS of 38 patients with HCV-associated lichen planus and 7 HCV-infected patients with normal oral mucosa treated at a medical center in Italy. Single-nucleotide polymorphisms in NRP2 (rs884000) and IGFBP4 (rs538399) were associated with risk of HCV-associated lichen planus (P lichen planus. The odds ratios for the minor alleles of rs884000, rs538399, and rs9461799 were 3.25 (95% confidence interval, 1.95-5.41), 0.40 (95% confidence interval, 0.25-0.63), and 2.15 (95% confidence interval, 1.41-3.28), respectively. In a GWAS of Japanese patients with HCV infection, we replicated associations between previously reported polymorphisms in HLA class II genes and risk for lichen planus. We also identified single-nucleotide polymorphisms in NRP2 and IGFBP4 loci that increase and reduce risk of lichen planus, respectively. These genetic variants might be used to identify patients with HCV infection who are at risk for lichen planus. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections.

    Science.gov (United States)

    Hertz, Tomer; Beatty, P Robert; MacMillen, Zachary; Killingbeck, Sarah S; Wang, Chunling; Harris, Eva

    2017-05-15

    Dengue is a global public health problem and is caused by four dengue virus (DENV) serotypes (DENV1-4). A major challenge in dengue vaccine development is that cross-reactive anti-DENV Abs can be protective or potentially increase disease via Ab-dependent enhancement. DENV nonstructural protein 1 (NS1) has long been considered a vaccine candidate as it avoids Ab-dependent enhancement. In this study, we evaluated survival to challenge in a lethal DENV vascular leak model in mice immunized with NS1 combined with aluminum and magnesium hydroxide, monophosphoryl lipid A + AddaVax, or Sigma adjuvant system+CpG DNA, compared with mice infected with a sublethal dose of DENV2 and mice immunized with OVA (negative control). We characterized Ab responses to DENV1, 2, and 3 NS1 using an Ag microarray tiled with 20-mer peptides overlapping by 15 aa and identified five regions of DENV NS1 with significant levels of Ab reactivity in the NS1 + monophosphoryl lipid A + AddaVax group. Additionally, we profiled the Ab responses to NS1 of humans naturally infected with DENV2 or DENV3 in serum samples from Nicaragua collected at acute, convalescent, and 12-mo timepoints. One region in the wing domain of NS1 was immunodominant in both mouse vaccination and human infection studies, and two regions were identified only in NS1-immunized mice; thus, vaccination can generate Abs to regions that are not targeted in natural infection and could provide additional protection against lethal DENV infection. Overall, we identified a small number of immunodominant regions, which were in functionally important locations on the DENV NS1 protein and are potential correlates of protection. Copyright © 2017 by The American Association of Immunologists, Inc.

  2. Receptor recognition and cross-species infections of SARS coronavirus.

    Science.gov (United States)

    Li, Fang

    2013-10-01

    Receptor recognition is a major determinant of the host range, cross-species infections, and pathogenesis of the severe acute respiratory syndrome coronavirus (SARS-CoV). A defined receptor-binding domain (RBD) in the SARS-CoV spike protein specifically recognizes its host receptor, angiotensin-converting enzyme 2 (ACE2). This article reviews the latest knowledge about how RBDs from different SARS-CoV strains interact with ACE2 from several animal species. Detailed research on these RBD/ACE2 interactions has established important principles on host receptor adaptations, cross-species infections, and future evolution of SARS-CoV. These principles may apply to other emerging animal viruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV). This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses". Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Novel viral genomes identified from six metagenomes reveal wide distribution of archaeal viruses and high viral diversity in terrestrial hot springs

    DEFF Research Database (Denmark)

    Islin, Sóley Ruth; Menzel, Peter; Krogh, Anders

    2016-01-01

    Limited by culture-dependent methods the number of viruses identified from thermophilic Archaea and Bacteria is still very small. In this study we retrieved viral sequences from six hot spring metagenomes isolated worldwide, revealing a wide distribution of four archaeal viral families, Ampullavi......Limited by culture-dependent methods the number of viruses identified from thermophilic Archaea and Bacteria is still very small. In this study we retrieved viral sequences from six hot spring metagenomes isolated worldwide, revealing a wide distribution of four archaeal viral families......, Ampullaviridae, Bicaudaviridae, Lipothrixviridae and Rudiviridae. Importantly, we identified ten complete or near complete viral genomes allowing, for the first time, an assessment of genome conservation and evolution of the Ampullaviridae family as well as Sulfolobus Monocaudavirus 1 (SMV1) related viruses....... Among the novel genomes, one belongs to a putative thermophilic virus infecting the bacterium Hydrogenobaculum, for which no virus has been reported in the literature. Moreover, a high viral diversity was observed in the metagenomes, especially among the Lipothrixviridae, as indicated by the large...

  4. Identifying crucial gaps in our knowledge of the life-history of avian influenza viruses - an Australian perspective

    NARCIS (Netherlands)

    Klaassen, M.R.J.; Hoye, B.J.; Roshier, D.

    2011-01-01

    We review our current knowledge of the epidemiology and ecology of avian influenza viruses (AIVs) in Australia in relation to the ecology of their hosts. Understanding the transmission and maintenance of low-pathogenic avian influenza (LPAI) viruses deserves scientific scrutiny because some of these

  5. Identifying blueberry germplasm that is slow to get Blueberry shock virus in the Pacific Northwest United States

    Science.gov (United States)

    Blueberry shock virus (BlShV) is a serious problem in blueberry production in the Pacific Northwest (PNW) region of North America. Infection occurs during bloom and the virus moves into other parts of the plant in an uneven but steady manner and may take several years to become fully systemic in mat...

  6. A systematic review of the literature to identify and quantify host and vector competence and abundance of Japanese Encephalitis Virus

    Science.gov (United States)

    Japanese Encephalitis virus (JEV) is a mosquito-borne arbovirus that causes endemic and epidemic encephalitis in Eastern and Southeastern Asia. Swine and wading birds serve as reservoirs for the virus, which can be transmitted to humans via mosquitos. Currently, there is no specific treatment availa...

  7. The SARS-CoV Fusion Peptide Forms an Extended Bipartite Fusion Platform that Perturbs Membrane Order in a Calcium-Dependent Manner.

    Science.gov (United States)

    Lai, Alex L; Millet, Jean K; Daniel, Susan; Freed, Jack H; Whittaker, Gary R

    2017-12-08

    Coronaviruses (CoVs) are a major infectious disease threat and include the pathogenic human pathogens of zoonotic origin: severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV). Entry of CoVs into host cells is mediated by the viral spike (S) protein, which is structurally categorized as a class I viral fusion protein, within the same group as influenza virus and HIV. However, S proteins have two distinct cleavage sites that can be activated by a much wider range of proteases. The exact location of the CoV fusion peptide (FP) has been disputed. However, most evidence suggests that the domain immediately downstream of the S2' cleavage site is the FP (amino acids 798-818 SFIEDLLFNKVTLADAGFMKQY for SARS-CoV, FP1). In our previous electron spin resonance spectroscopic studies, the membrane-ordering effect of influenza virus, HIV, and Dengue virus FPs has been consistently observed. In this study, we used this effect as a criterion to identify and characterize the bona fide SARS-CoV FP. Our results indicate that both FP1 and the region immediately downstream (amino acids 816-835 KQYGECLGDINARDLICAQKF, FP2) induce significant membrane ordering. Furthermore, their effects are calcium dependent, which is consistent with in vivo data showing that calcium is required for SARS-CoV S-mediated fusion. Isothermal titration calorimetry showed a direct interaction between calcium cations and both FPs. This Ca2+-dependency membrane ordering was not observed with influenza FP, indicating that the CoV FP exhibits a mechanistically different behavior. Membrane-ordering effects are greater and penetrate deeper into membranes when FP1 and FP2 act in a concerted manner, suggesting that they form an extended fusion "platform." Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Bistatic SAR: Imagery & Image Products.

    Energy Technology Data Exchange (ETDEWEB)

    Yocky, David A.; Wahl, Daniel E.; Jakowatz, Charles V,

    2014-10-01

    While typical SAR imaging employs a co-located (monostatic) RADAR transmitter and receiver, bistatic SAR imaging separates the transmitter and receiver locations. The transmitter and receiver geometry determines if the scattered signal is back scatter, forward scatter, or side scatter. The monostatic SAR image is backscatter. Therefore, depending on the transmitter/receiver collection geometry, the captured imagery may be quite different that that sensed at the monostatic SAR. This document presents imagery and image products formed from captured signals during the validation stage of the bistatic SAR research. Image quality and image characteristics are discussed first. Then image products such as two-color multi-view (2CMV) and coherent change detection (CCD) are presented.

  9. Ambiguities analysis in SAR tomography

    Science.gov (United States)

    Wang, Ziwei; Zhang, Hong; Wang, Chao; Tang, Yixian; Zhang, Bo

    2014-10-01

    Synthetic aperture radar tomography (TomoSAR) is typically used to retrieve elevation, deformation, and other key information by separating scatters of the same slant range in multiple baseline SAR images. In this paper, we investigate two kinds of ambiguities for TomoSAR. Rank-1 ambiguity, as the first one we concerned, is due to the baseline distribution of the SAR image dataset which makes the steering matrix out of full rank. It will result in false alarms appearing in a permanent distance. However, an example using the TomoSAR imaging parameters shows this ambiguity makes no sense in most cases. The second ambiguity refers to the coherence of scatters contained in one pixel. In simulation experiment, the coherence will enhance the side lobes of the spectrum, even make the real peaks fused.

  10. Efficient Culture Adaptation of Hepatitis C Virus Recombinants with Genotype-Specific Core-NS2 by Using Previously Identified Mutations

    DEFF Research Database (Denmark)

    Scheel, Troels Kasper Høyer; Gottwein, Judith M; Carlsen, Thomas H R

    2011-01-01

    Hepatitis C virus (HCV) is an important cause of chronic liver disease, and interferon-based therapy cures only 40 to 80% of patients, depending on HCV genotype. Research was accelerated by genotype 2a (strain JFH1) infectious cell culture systems. We previously developed viable JFH1-based...... (HC-TN and DH6), 1b (DH1 and DH5), and 3a (DBN) isolates, using previously identified adaptive mutations. Introduction of mutations from isolates of the same subtype either led to immediate efficient virus production or accelerated culture adaptation. The DH6 and DH5 recombinants without introduced......) but not to ED43 (4a). The mutations permitting robust virus production in Huh7.5 cells had no apparent effect on viral replication but allowed efficient assembly of intracellular infectious HCV for adapted novel or previously developed recombinants. In conclusion, previously identified mutations permitted...

  11. Real-Time qPCR Identifies Suitable Reference Genes for Borna Disease Virus-Infected Rat Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Lujun Zhang

    2014-11-01

    Full Text Available Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR is the most commonly-used technique to identify gene expression profiles. The selection of stably expressed reference genes is a prerequisite to properly evaluating gene expression. Here, the suitability of commonly-used reference genes in normalizing RT-qPCR assays of mRNA expression in cultured rat cortical neurons infected with Borna disease virus (BDV was assessed. The expressions of eight commonly-used reference genes were comparatively analyzed in BDV-infected rat cortical neurons and non-infected control neurons mainly across 9 and 12 days post-infection. These reference genes were validated by RT-qPCR and separately ranked by four statistical algorithms: geNorm, NormFinder, BestKeeper and the comparative delta-Ct method. Then, the RankAggreg package was used to construct consensus rankings. ARBP was found to be the most stable internal control gene at Day 9, and ACTB at Day 12. As the assessment of the validity of the selected reference genes confirms the suitability of applying a combination of the two most stable references genes, combining the two most stable genes for normalization of RT-qPCR studies in BDV-infected rat cortical neurons is recommended at each time point. This study can contribute to improving BDV research by providing the means by which to obtain more reliable and accurate gene expression measurements.

  12. Real-time qPCR identifies suitable reference genes for Borna disease virus-infected rat cortical neurons.

    Science.gov (United States)

    Zhang, Lujun; Liu, Siwen; Zhang, Liang; You, Hongmin; Huang, Rongzhong; Sun, Lin; He, Peng; Chen, Shigang; Zhang, Hong; Xie, Peng

    2014-11-26

    Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) is the most commonly-used technique to identify gene expression profiles. The selection of stably expressed reference genes is a prerequisite to properly evaluating gene expression. Here, the suitability of commonly-used reference genes in normalizing RT-qPCR assays of mRNA expression in cultured rat cortical neurons infected with Borna disease virus (BDV) was assessed. The expressions of eight commonly-used reference genes were comparatively analyzed in BDV-infected rat cortical neurons and non-infected control neurons mainly across 9 and 12 days post-infection. These reference genes were validated by RT-qPCR and separately ranked by four statistical algorithms: geNorm, NormFinder, BestKeeper and the comparative delta-Ct method. Then, the RankAggreg package was used to construct consensus rankings. ARBP was found to be the most stable internal control gene at Day 9, and ACTB at Day 12. As the assessment of the validity of the selected reference genes confirms the suitability of applying a combination of the two most stable references genes, combining the two most stable genes for normalization of RT-qPCR studies in BDV-infected rat cortical neurons is recommended at each time point. This study can contribute to improving BDV research by providing the means by which to obtain more reliable and accurate gene expression measurements.

  13. Small RNA profiling of influenza A virus-infected cells identifies miR-449b as a regulator of histone deacetylase 1 and interferon beta.

    Directory of Open Access Journals (Sweden)

    William A Buggele

    Full Text Available The mammalian antiviral response relies on the alteration of cellular gene expression, to induce the production of antiviral effectors and regulate their activities. Recent research has indicated that virus infections can induce the accumulation of cellular microRNA (miRNA species that influence the stability of host mRNAs and their protein products. To determine the potential for miRNA regulation of cellular responses to influenza A virus infection, small RNA profiling was carried out using next generation sequencing. Comparison of miRNA expression profiles in uninfected human A549 cells to cells infected with influenza A virus strains A/Udorn/72 and A/WSN/33, revealed virus-induced changes in miRNA abundance. Gene expression analysis identified mRNA targets for a cohort of highly inducible miRNAs linked to diverse cellular functions. Experiments demonstrate that the histone deacetylase, HDAC1, can be regulated by influenza-inducible miR-449b, resulting in altered mRNA and protein levels. Expression of miR-449b enhances virus and poly(I:C activation of the IFNβ promoter, a process known to be negatively regulated by HDAC1. These findings demonstrate miRNA induction by influenza A virus infection and elucidate an example of miRNA control of antiviral gene expression in human cells, defining a role for miR-449b in regulation of HDAC1 and antiviral cytokine signaling.

  14. Viral metagenomic analysis of bushpigs (Potamochoerus larvatus in Uganda identifies novel variants of Porcine parvovirus 4 and Torque teno sus virus 1 and 2

    Directory of Open Access Journals (Sweden)

    Blomström Anne-Lie

    2012-09-01

    Full Text Available Abstract Background As a result of rapidly growing human populations, intensification of livestock production and increasing exploitation of wildlife habitats for animal agriculture, the interface between wildlife, livestock and humans is expanding, with potential impacts on both domestic animal and human health. Wild animals serve as reservoirs for many viruses, which may occasionally result in novel infections of domestic animals and/or the human population. Given this background, we used metagenomics to investigate the presence of viral pathogens in sera collected from bushpigs (Potamochoerus larvatus, a nocturnal species of wild Suid known to move between national parks and farmland, in Uganda. Results Application of 454 pyrosequencing demonstrated the presence of Torque teno sus virus (TTSuV, porcine parvovirus 4 (PPV4, porcine endogenous retrovirus (PERV, a GB Hepatitis C–like virus, and a Sclerotinia hypovirulence-associated-like virus in sera from the bushpigs. PCR assays for each specific virus combined with Sanger sequencing revealed two TTSuV-1 variants, one TTSuV-2 variant as well as PPV4 in the serum samples and thereby confirming the findings from the 454 sequencing. Conclusions Using a viral metagenomic approach we have made an initial analysis of viruses present in bushpig sera and demonstrated for the first time the presence of PPV4 in a wild African Suid. In addition we identified novel variants of TTSuV-1 and 2 in bushpigs.

  15. Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions, and chemical reagents

    OpenAIRE

    Kariwa, Hiroaki; Fujii, Nobuhiro; TAKASHIMA, Ikuo

    2004-01-01

    products, a number of other chemical agents, and various physical conditions were evaluated for their ability to inactivate the severe acute respiratory syndrome coronavirus (SARS-CoV). Treatment of SARS-CoV with PVP-I products for 2 min reduced the virus infectivity from 1.17 x 10⁶ TCID₅₀/ml to below the detectable level. The efficacy of 70% ethanol was equivalent to that of PVP-I products. Fixation of SARS-CoV-infected Vero E6 cells with a fixative including formalin, glutaraldehyde, methan...

  16. Machine learning models identify molecules active against the Ebola virus in vitro [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2017-01-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  17. Regulatory network analysis of Epstein-Barr virus identifies functional modules and hub genes involved in infectious mononucleosis.

    Science.gov (United States)

    Poorebrahim, Mansour; Salarian, Ali; Najafi, Saeideh; Abazari, Mohammad Foad; Aleagha, Maryam Nouri; Dadras, Mohammad Nasr; Jazayeri, Seyed Mohammad; Ataei, Atousa; Poortahmasebi, Vahdat

    2017-05-01

    Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and establishes lifetime infection associated with a variety of cancers and autoimmune diseases. The aim of this study was to develop an integrative gene regulatory network (GRN) approach and overlying gene expression data to identify the representative subnetworks for IM and EBV latent infection (LI). After identifying differentially expressed genes (DEGs) in both IM and LI gene expression profiles, functional annotations were applied using gene ontology (GO) and BiNGO tools, and construction of GRNs, topological analysis and identification of modules were carried out using several plugins of Cytoscape. In parallel, a human-EBV GRN was generated using the Hu-Vir database for further analyses. Our analysis revealed that the majority of DEGs in both IM and LI were involved in cell-cycle and DNA repair processes. However, these genes showed a significant negative correlation in the IM and LI states. Furthermore, cyclin-dependent kinase 2 (CDK2) - a hub gene with the highest centrality score - appeared to be the key player in cell cycle regulation in IM disease. The most significant functional modules in the IM and LI states were involved in the regulation of the cell cycle and apoptosis, respectively. Human-EBV network analysis revealed several direct targets of EBV proteins during IM disease. Our study provides an important first report on the response to IM/LI EBV infection in humans. An important aspect of our data was the upregulation of genes associated with cell cycle progression and proliferation.

  18. Machine learning models identify molecules active against the Ebola virus in vitro [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2016-01-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  19. Machine learning models identify molecules active against the Ebola virus in vitro [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2015-10-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  20. Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV replication.

    Directory of Open Access Journals (Sweden)

    Ji'an Pan

    Full Text Available Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12 provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins.

  1. Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies.

    Science.gov (United States)

    Moni, Mohammad Ali; Liò, Pietro

    2014-10-24

    Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says "I'd rather have HIV than diabetes" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable

  2. Novel immune-modulator identified by a rapid, functional screen of the parapoxvirus ovis (Orf virus genome

    Directory of Open Access Journals (Sweden)

    McGuire Michael J

    2012-01-01

    Full Text Available Abstract Background The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach. Results The genome of Parapoxvirus ovis (Orf virus was sequenced, annotated, and then used to PCR-amplify its open-reading-frames. Employing a cloning-independent protocol, a viral expression-library was rapidly built and arrayed into sub-library pools. These were directly delivered into mice as expressible cassettes and assayed for an immune-modulating activity associated with parapoxvirus infection. The product of the B2L gene, a homolog of vaccinia F13L, was identified as the factor eliciting immune cell accumulation at sites of skin inoculation. Administration of purified B2 protein also elicited immune cell accumulation activity, and additionally was found to serve as an adjuvant for antigen-specific responses. Co-delivery of the B2L gene with an influenza gene-vaccine significantly improved protection in mice. Furthermore, delivery of the B2L expression construct, without antigen, non-specifically reduced tumor growth in murine models of cancer. Conclusion A streamlined, functional approach to genome-wide screening of a biological activity in vivo is presented. Its application to screening in mice for an immune activity elicited by the pathogen genome of Parapoxvirus ovis yielded a novel immunomodulator. In this inverted discovery method, it was possible to identify the adjuvant responsible for a function of interest prior to a mechanistic study of the adjuvant. The non-specific immune activity of this modulator, B2, is similar to that associated with administration of inactivated particles to a host or to a live viral infection. Administration

  3. Using airborne and satellite SAR for wake mapping offshore

    Science.gov (United States)

    Christiansen, Merete B.; Hasager, Charlotte B.

    2006-09-01

    Offshore wind energy is progressing rapidly around Europe. One of the latest initiatives is the installation of multiple wind farms in clusters to share cables and maintenance costs and to fully exploit premium wind resource sites. For siting of multiple nearby wind farms, the wind turbine wake effect must be considered. Synthetic aperture radar (SAR) is an imaging remote sensing technique which offers a unique opportunity to describe spatial variations of wind speed offshore. For the first time an airborne SAR instrument was used for data acquisition over a large offshore wind farm. The aim was to identify the turbine wake effect from SAR-derived wind speed maps as a downstream region of reduced wind speed. The aircraft SAR campaign was conducted on 12 October 2003 over the wind farm at Horns Rev in the North Sea. Nearly simultaneous measurements were acquired over the area by the SAR on board the ERS-2 satellite. In addition, meteorological data were collected. Both aircraft and satellite SAR-derived wind speed maps showed significant velocity deficits downstream of the wind farm. Wind speed maps retrieved from aircraft SAR suggested deficits of up to 20% downstream of the last turbine, whereas satellite SAR-derived maps showed deficits of the order of 10%. The difference originated partly from the two different reference methods used for normalization of measured wind speeds. The detected region of reduced wind speed had the same width as the wind turbine array, indicating a low degree of horizontal wake dispersion. The downstream wake extent was approximately 10 km, which corresponds well with results from previous studies and with wake model predictions. Copyright

  4. Automatic detection and mapping of oil spill using SAR images

    Energy Technology Data Exchange (ETDEWEB)

    Assilzadeh, H.; Gao, Y. [Calgary Univ., AB (Canada). Schulich School of Engineering, Dept. of Geomatics Engineering

    2008-07-01

    Satellite remote sensing can act as a supplement for other aerial observations for offshore oil spills that cover vast areas of the marine environment. A method for automatic detection and mapping of oil spills in synthetic aperture radar (SAR) images was presented. The proposed SAR framework includes detecting and classifying spilled areas based on texture analysis, thresholding, Gamma filtering and unsupervised classification. SAR is suitable for spills in situations when the oil cannot be seen or discriminated against the background. The automatic processing of a radar image for oil spill detection and delineation in seawater and coastal areas was demonstrated in this paper. Radar signatures were shown to be effective in distinguishing different regions of an oil spill, and classifying the oil spill region into 3 classes according to spill thicknesses. Classification is based on a gradient of back scattering value in spilled regions through different oil concentrations. However, there are some limitations regarding weather conditions in identifying oil slicks. At high winds, the oil may be washed down into the sea, leaving no surface effect in the SAR image. In addition, since SAR signals cannot be received at very low winds, no slicks can be observed. Experienced operators are needed to distinguish false alarms that may occur when processing oil spill look-alikes such as natural surfactants, sea alga and grease ice. The proposed SAR framework was shown to provide valuable information about oil spill scenarios and the extent of polluted areas. 26 refs., 4 figs.

  5. High Resolution Processing with an Active Phased Array SAR

    NARCIS (Netherlands)

    Nijenboer, F.J.; Otten, M.P.G.

    1999-01-01

    The Dutch PHARUS system is a polarimetric active phased array SAR capable of performing advanced SAR modes. Advanced SAR modes that are being investigated are: spotlight SAR, sliding spotlight SAR, stepped frequency SAR and interferometric SAR. The flight experiments and automatic beam steering

  6. Liver regeneration signature in hepatitis B virus (HBV-associated acute liver failure identified by gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Oriel Nissim

    Full Text Available The liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC. The dramatic clinical course of acute liver failure (ALF has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV-associated ALF.Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients and submassive hepatic necrosis (SHN; 2 patients. We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7, whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process.Our data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between

  7. Virtual screening approach to identifying influenza virus neuraminidase inhibitors using molecular docking combined with machine-learning-based scoring function.

    Science.gov (United States)

    Zhang, Li; Ai, Hai-Xin; Li, Shi-Meng; Qi, Meng-Yuan; Zhao, Jian; Zhao, Qi; Liu, Hong-Sheng

    2017-10-10

    In recent years, an epidemic of the highly pathogenic avian influenza H7N9 virus has persisted in China, with a high mortality rate. To develop novel anti-influenza therapies, we have constructed a machine-learning-based scoring function (RF-NA-Score) for the effective virtual screening of lead compounds targeting the viral neuraminidase (NA) protein. RF-NA-Score is more accurate than RF-Score, with a root-mean-square error of 1.46, Pearson's correlation coefficient of 0.707, and Spearman's rank correlation coefficient of 0.707 in a 5-fold cross-validation study. The performance of RF-NA-Score in a docking-based virtual screening of NA inhibitors was evaluated with a dataset containing 281 NA inhibitors and 322 noninhibitors. Compared with other docking-rescoring virtual screening strategies, rescoring with RF-NA-Score significantly improved the efficiency of virtual screening, and a strategy that averaged the scores given by RF-NA-Score, based on the binding conformations predicted with AutoDock, AutoDock Vina, and LeDock, was shown to be the best strategy. This strategy was then applied to the virtual screening of NA inhibitors in the SPECS database. The 100 selected compounds were tested in an in vitro H7N9 NA inhibition assay, and two compounds with novel scaffolds showed moderate inhibitory activities. These results indicate that RF-NA-Score improves the efficiency of virtual screening for NA inhibitors, and can be used successfully to identify new NA inhibitor scaffolds. Scoring functions specific for other drug targets could also be established with the same method.

  8. Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination.

    Directory of Open Access Journals (Sweden)

    Jill M Brooks

    2016-04-01

    Full Text Available Epstein-Barr virus, a B-lymphotropic herpesvirus, is the cause of infectious mononucleosis, has strong aetiologic links with several malignancies and has been implicated in certain autoimmune diseases. Efforts to develop a prophylactic vaccine to prevent or reduce EBV-associated disease have, to date, focused on the induction of neutralising antibody responses. However, such vaccines might be further improved by inducing T cell responses capable of recognising and killing recently-infected B cells. In that context, EBNA2, EBNA-LP and BHRF1 are the first viral antigens expressed during the initial stage of B cell growth transformation, yet have been poorly characterised as CD8+ T cell targets. Here we describe CD8+ T cell responses against each of these three "first wave" proteins, identifying target epitopes and HLA restricting alleles. While EBNA-LP and BHRF1 each contained one strong CD8 epitope, epitopes within EBNA2 induced immunodominant responses through several less common HLA class I alleles (e.g. B*3801 and B*5501, as well as subdominant responses through common class I alleles (e.g. B7 and C*0304. Importantly, such EBNA2-specific CD8+ T cells recognised B cells within the first day post-infection, prior to CD8+ T cells against well-characterised latent target antigens such as EBNA3B or LMP2, and effectively inhibited outgrowth of EBV-transformed B cell lines. We infer that "first wave" antigens of the growth-transforming infection, especially EBNA2, constitute potential CD8+ T cell immunogens for inclusion in prophylactic EBV vaccine design.

  9. Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates

    Science.gov (United States)

    Smits, Saskia L.; de Lang, Anna; van den Brand, Judith M. A.; Leijten, Lonneke M.; van IJcken, Wilfred F.; Eijkemans, Marinus J. C.; van Amerongen, Geert; Kuiken, Thijs; Andeweg, Arno C.; Osterhaus, Albert D. M. E.; Haagmans, Bart L.

    2010-01-01

    The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI. PMID:20140198

  10. In vitro and in vivo studies identify important features of dengue virus pr-E protein interactions.

    Directory of Open Access Journals (Sweden)

    Aihua Zheng

    2010-10-01

    Full Text Available Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors.

  11. The SARS-unique domain (SUD of SARS coronavirus contains two macrodomains that bind G-quadruplexes.

    Directory of Open Access Journals (Sweden)

    Jinzhi Tan

    2009-05-01

    Full Text Available Since the outbreak of severe acute respiratory syndrome (SARS in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV, the non-structural proteins (Nsps, have been determined. However, within the large Nsp3 (1922 amino-acid residues, the structure and function of the so-called SARS-unique domain (SUD have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389-652 ("SUD(core" of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 A resolution, respectively revealed that SUD(core forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD(core as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5-6 nucleotides, but more extended G-stretches are found in the 3'-nontranslated regions of mRNAs coding for certain host-cell proteins

  12. Obstacles and advances in SARS vaccine development.

    Science.gov (United States)

    Taylor, Deborah R

    2006-02-13

    The emergence of the severe acute respiratory syndrome (SARS) that resulted in a pandemic in 2003 spurred a flurry of interest in the development of vaccines to prevent and treat the potentially deadly viral infection. Researchers around the world pooled their scientific resources and shared early data in an unprecedented manner in light of the impending public health crisis. There are still large gaps in knowledge about the pathogenesis of this virus. While significant advances have been made in the development of animal models, the practicality of their use may be hampered by a lack of pathological similarity with human disease. Described here are issues related to progress in vaccine development and the obstacles that lie ahead for both researchers and regulatory agencies.

  13. SAR calculation using FDTD simulations

    OpenAIRE

    Ferro, Francisco Nabais; Pinto, Guilherme Taveira; Pinho, Pedro

    2009-01-01

    The main intend of this work, is to determinate the Specific Absorption Rate (SAR) on human head tissues exposed to radiation caused by sources of 900 and 1800MHz, since those are the typical frequencies for mobile communications systems nowadays. In order to determinate the SAR, has been used the FDTD (Finite Difference Time Domain), which is a numeric method in time domain, obtained from the Maxwell equations in differential mode. In order to do this, a computational model from the human he...

  14. A Real-Time PCR Assay to Identify and Discriminate Among Wild-Type and Vaccine Strains of Varicella-Zoster Virus and Herpes Simplex Virus in Clinical Specimens, and Comparison With the Clinical Diagnoses

    Science.gov (United States)

    Harbecke, Ruth; Oxman, Michael N.; Arnold, Beth A.; Ip, Charlotte; Johnson, Gary R.; Levin, Myron J.; Gelb, Lawrence D.; Schmader, Kenneth E.; Straus, Stephen E.; Wang, Hui; Wright, Peter F.; Pachucki, Constance T.; Gershon, Anne A.; Arbeit, Robert D.; Davis, Larry E.; Simberkoff, Michael S.; Weinberg, Adriana; Williams, Heather M.; Cheney, Carol; Petrukhin, Luba; Abraham, Katalin G.; Shaw, Alan; Manoff, Susan; Antonello, Joseph M.; Green, Tina; Wang, Yue; Tan, Charles; Keller, Paul M.

    2014-01-01

    A real-time PCR assay was developed to identify varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA in clinical specimens from subjects with suspected herpes zoster (HZ; shingles). Three sets of primers and probes were used in separate PCR reactions to detect and discriminate among wild-type VZV (VZV-WT), Oka vaccine strain VZV (VZV-Oka), and HSV DNA, and the reaction for each virus DNA was multiplexed with primers and probe specific for the human β-globin gene to assess specimen adequacy. Discrimination of all VZV-WT strains, including Japanese isolates and the Oka parent strain, from VZV-Oka was based upon a single nucleotide polymorphism at position 106262 in ORF 62, resulting in preferential amplification by the homologous primer pair. The assay was highly sensitive and specific for the target virus DNA, and no cross-reactions were detected with any other infectious agent. With the PCR assay as the gold standard, the sensitivity of virus culture was 53% for VZV and 77% for HSV. There was 92% agreement between the clinical diagnosis of HZ by the Clinical Evaluation Committee and the PCR assay results. PMID:19475609

  15. In vitro screen of a small molecule inhibitor drug library identifies multiple compounds that synergize with oncolytic myxoma virus against human brain tumor-initiating cells.

    Science.gov (United States)

    McKenzie, Brienne A; Zemp, Franz J; Pisklakova, Alexandra; Narendran, Aru; McFadden, Grant; Lun, Xueqing; Kenchappa, Rajappa S; Kurz, Ebba U; Forsyth, Peter A

    2015-08-01

    Brain tumor-initiating cells (BTICs) are stem-like cells hypothesized to form a disease reservoir that mediates tumor recurrence in high-grade gliomas. Oncolytic virotherapy uses replication-competent viruses to target and kill malignant cells and has been evaluated in clinic for glioma therapy with limited results. Myxoma virus (MyxV) is a safe and highly effective oncolytic virus (OV) in conventional glioma models but, as seen with other OVs, is only modestly effective for patient-derived BTICs. The objective of this study was to determine whether MyxV treatment against human BTICs could be improved by combining chemotherapeutics and virotherapy. A 73-compound library of drug candidates in clinical use or preclinical development was screened to identify compounds that sensitize human BTICs to MyxV treatment in vitro, and synergy was evaluated mathematically in lead compounds using Chou-Talalay analyses. The effects of combination therapy on viral gene expression and viral replication were also assessed. Eleven compounds that enhance MyxV efficacy were identified, and 6 were shown to synergize with the virus using Chou-Talalay analyses. Four of the synergistic compounds were shown to significantly increase viral gene expression, indicating a potential mechanism for synergy. Three highly synergistic compounds (axitinib, a VEGFR inhibitor; rofecoxib, a cyclooxygenase-2 inhibitor; and pemetrexed, a folate anti-metabolite) belong to classes of compounds that have not been previously shown to synergize with oncolytic viruses in vitro. This study has identified multiple novel drug candidates that synergistically improve MyxV efficacy in a preclinical BTIC glioma model. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. The First Identified Citrus tristeza virus Isolate of Turkey Contains a Mixture of Mild and Severe Strains

    Directory of Open Access Journals (Sweden)

    Bayram Çevik

    2013-03-01

    Full Text Available The presence of Citrus tristeza virus (CTV has previously been reported in citrus growing regions of Turkey. All serologically and biologically characterized isolates including Iğdır, which was the first identified CTV isolates from Turkey, were considered mild isolates. In this study, molecular characteristics of the Iğdır isolate were determined by different methods. Analysis of the Iğdır isolate by western blot and BD-RT-PCR assays showed the presence of MCA13 epitope, predominantly found in severe isolates, in the Iğdır isolate revealing that it contains a severe component. For further characterization, the coat protein (CP and the RNA-dependent RNA polymerase (RdRp genes representing the 3′ and 5′ half of CTV genome, respectively, were amplified from dsRNA by RT-PCR. Both genes were cloned separately and two clones for each gene were sequenced. Comparisons of nucleotide and deduced amino acid sequences showed that while two CP gene sequences were identical, two RdRp clones showed only 90% and 91% sequence identity in their nucleotide and amino acid sequences, respectively, suggesting a mixed infection with different strains. Phylogenetic analyses of the CP and RdRp genes of Iğdır isolate with previously characterized CTV isolates from different citrus growing regions showed that the CP gene was clustered with NZRB-TH30, a resistance breaking isolate from New Zealand, clearly showing the presence of severe component. Furthermore, two different clones of the RdRp gene were clustered separately with different CTV isolates with a diverse biological activity. While the RdRp-1 was clustered with T30 and T385, two well-characterized mild isolates from Florida and Spain, respectively, the RdRp-2 was most closely related to NZRB-G90 and NZRB-TH30, two well-characterized resistance breaking and stem pitting (SP isolates from New Zealand confirming the mixed infection. These results clearly demonstrated that the Iğdır isolate, which

  17. The First Identified Citrus tristeza virus Isolate of Turkey Contains a Mixture of Mild and Severe Strains.

    Science.gov (United States)

    Cevik, Bayram; Yardimci, Nejla; Korkmaz, Savaş

    2013-03-01

    The presence of Citrus tristeza virus (CTV) has previously been reported in citrus growing regions of Turkey. All serologically and biologically characterized isolates including Iğdır, which was the first identified CTV isolates from Turkey, were considered mild isolates. In this study, molecular characteristics of the Iğdır isolate were determined by different methods. Analysis of the Iğdır isolate by western blot and BD-RT-PCR assays showed the presence of MCA13 epitope, predominantly found in severe isolates, in the Iğdır isolate revealing that it contains a severe component. For further characterization, the coat protein (CP) and the RNA-dependent RNA polymerase (RdRp) genes representing the 3' and 5' half of CTV genome, respectively, were amplified from dsRNA by RT-PCR. Both genes were cloned separately and two clones for each gene were sequenced. Comparisons of nucleotide and deduced amino acid sequences showed that while two CP gene sequences were identical, two RdRp clones showed only 90% and 91% sequence identity in their nucleotide and amino acid sequences, respectively, suggesting a mixed infection with different strains. Phylogenetic analyses of the CP and RdRp genes of Iğdır isolate with previously characterized CTV isolates from different citrus growing regions showed that the CP gene was clustered with NZRB-TH30, a resistance breaking isolate from New Zealand, clearly showing the presence of severe component. Furthermore, two different clones of the RdRp gene were clustered separately with different CTV isolates with a diverse biological activity. While the RdRp-1 was clustered with T30 and T385, two well-characterized mild isolates from Florida and Spain, respectively, the RdRp-2 was most closely related to NZRB-G90 and NZRB-TH30, two well-characterized resistance breaking and stem pitting (SP) isolates from New Zealand confirming the mixed infection. These results clearly demonstrated that the Iğdır isolate, which was previously

  18. Analysis of intraviral protein-protein interactions of the SARS coronavirus ORFeome.

    Directory of Open Access Journals (Sweden)

    Albrecht von Brunn

    2007-05-01

    Full Text Available The severe acute respiratory syndrome coronavirus (SARS-CoV genome is predicted to encode 14 functional open reading frames, leading to the expression of up to 30 structural and non-structural protein products. The functions of a large number of viral ORFs are poorly understood or unknown. In order to gain more insight into functions and modes of action and interaction of the different proteins, we cloned the viral ORFeome and performed a genome-wide analysis for intraviral protein interactions and for intracellular localization. 900 pairwise interactions were tested by yeast-two-hybrid matrix analysis, and more than 65 positive non-redundant interactions, including six self interactions, were identified. About 38% of interactions were subsequently confirmed by CoIP in mammalian cells. Nsp2, nsp8 and ORF9b showed a wide range of interactions with other viral proteins. Nsp8 interacts with replicase proteins nsp2, nsp5, nsp6, nsp7, nsp8, nsp9, nsp12, nsp13 and nsp14, indicating a crucial role as a major player within the replication complex machinery. It was shown by others that nsp8 is essential for viral replication in vitro, whereas nsp2 is not. We show that also accessory protein ORF9b does not play a pivotal role for viral replication, as it can be deleted from the virus displaying normal plaque sizes and growth characteristics in Vero cells. However, it can be expected to be important for the virus-host interplay and for pathogenicity, due to its large number of interactions, by enhancing the global stability of the SARS proteome network, or play some unrealized role in regulating protein-protein interactions. The interactions identified provide valuable material for future studies.

  19. Hepatitis virus protein X-Phenylalanine Hydroxylase fusion proteins identified in PKU mice treated with AAV-WPRE vectors

    Science.gov (United States)

    Utilizing the Pahenu2 mouse model for phenylketonuria (PKU), we developed an improved expression vector containing the Woodchuck Hepatitis Virus post-transcriptional regulatory element inserted into a rAAV-mPAH construct (rAAV-mPAH-WPRE) for treatment of PKU. Following portal vein delivery of these ...

  20. Multiple viral infections in Agaricus bisporus - Characterisation of 18 unique RNA viruses and 8 ORFans identified by deep sequencing.

    Science.gov (United States)

    Deakin, Gregory; Dobbs, Edward; Bennett, Julie M; Jones, Ian M; Grogan, Helen M; Burton, Kerry S

    2017-05-26

    Thirty unique non-host RNAs were sequenced in the cultivated fungus, Agaricus bisporus, comprising 18 viruses each encoding an RdRp domain with an additional 8 ORFans (non-host RNAs with no similarity to known sequences). Two viruses were multipartite with component RNAs showing correlative abundances and common 3' motifs. The viruses, all positive sense single-stranded, were classified into diverse orders/families. Multiple infections of Agaricus may represent a diverse, dynamic and interactive viral ecosystem with sequence variability ranging over 2 orders of magnitude and evidence of recombination, horizontal gene transfer and variable fragment numbers. Large numbers of viral RNAs were detected in multiple Agaricus samples; up to 24 in samples symptomatic for disease and 8-17 in asymptomatic samples, suggesting adaptive strategies for co-existence. The viral composition of growing cultures was dynamic, with evidence of gains and losses depending on the environment and included new hypothetical viruses when compared with the current transcriptome and EST databases. As the non-cellular transmission of mycoviruses is rare, the founding infections may be ancient, preserved in wild Agaricus populations, which act as reservoirs for subsequent cell-to-cell infection when host populations are expanded massively through fungiculture.

  1. Protection from SARS coronavirus conferred by live measles vaccine expressing the spike glycoprotein.

    Science.gov (United States)

    Escriou, Nicolas; Callendret, Benoît; Lorin, Valérie; Combredet, Chantal; Marianneau, Philippe; Février, Michèle; Tangy, Frédéric

    2014-03-01

    The recent identification of a novel human coronavirus responsible of a SARS-like illness in the Middle-East a decade after the SARS pandemic, demonstrates that reemergence of a SARS-like coronavirus from an animal reservoir remains a credible threat. Because SARS is contracted by aerosolized contamination of the respiratory tract, a vaccine inducing mucosal long-term protection would be an asset to control new epidemics. To this aim, we generated live attenuated recombinant measles vaccine (MV) candidates expressing either the membrane-anchored SARS-CoV spike (S) protein or its secreted soluble ectodomain (Ssol). In mice susceptible to measles virus, recombinant MV expressing the anchored full-length S induced the highest titers of neutralizing antibodies and fully protected immunized animals from intranasal infectious challenge with SARS-CoV. As compared to immunization with adjuvanted recombinant Ssol protein, recombinant MV induced stronger and Th1-biased responses, a hallmark of live attenuated viruses and a highly desirable feature for an antiviral vaccine. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS.

    Science.gov (United States)

    Demurtas, Olivia C; Massa, Silvia; Illiano, Elena; De Martinis, Domenico; Chan, Paul K S; Di Bonito, Paola; Franconi, Rosella

    2016-01-01

    Severe acute respiratory syndrome (SARS) is a dangerous infection with pandemic potential. It emerged in 2002 and its aetiological agent, the SARS Coronavirus (SARS-CoV), crossed the species barrier to infect humans, showing high morbidity and mortality rates. No vaccines are currently licensed for SARS-CoV and important efforts have been performed during the first outbreak to develop diagnostic tools. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. For the M protein, this is the first description of production in plants, while for plant-derived N protein we demonstrate that it is recognized by sera of patients from the SARS outbreak in Hong Kong in 2003. The availability of recombinant N and M proteins from plants opens the way to further evaluation of their potential utility for the development of diagnostic and protection/therapy tools to be quickly manufactured, at low cost and with minimal risk, to face potential new highly infectious SARS-CoV outbreaks.

  3. The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis.

    Science.gov (United States)

    Venkataraman, Thiagarajan; Frieman, Matthew B

    2017-07-01

    Many survivors of the 2003 outbreak of severe acute respiratory syndrome (SARS) developed residual pulmonary fibrosis with increased severity seen in older patients. Autopsies of patients that died from SARS also showed fibrosis to varying extents. Pulmonary fibrosis can be occasionally seen as a consequence to several respiratory viral infections but is much more common after a SARS coronavirus (SARS-CoV) infection. Given the threat of future outbreaks of severe coronavirus disease, including Middle East respiratory syndrome (MERS), it is important to understand the mechanisms responsible for pulmonary fibrosis, so as to support the development of therapeutic countermeasures and mitigate sequelae of infection. In this article, we summarize pulmonary fibrotic changes observed after a SARS-CoV infection, discuss the extent to which other respiratory viruses induce fibrosis, describe available animal models to study the development of SARS-CoV induced fibrosis and review evidence that pulmonary fibrosis is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signaling. We summarize work from our group and others indicating that inhibiting EGFR signaling may prevent an excessive fibrotic response to SARS-CoV and other respiratory viral infections and propose directions for future research. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS

    Science.gov (United States)

    Demurtas, Olivia C.; Massa, Silvia; Illiano, Elena; De Martinis, Domenico; Chan, Paul K. S.; Di Bonito, Paola; Franconi, Rosella

    2016-01-01

    Severe acute respiratory syndrome (SARS) is a dangerous infection with pandemic potential. It emerged in 2002 and its aetiological agent, the SARS Coronavirus (SARS-CoV), crossed the species barrier to infect humans, showing high morbidity and mortality rates. No vaccines are currently licensed for SARS-CoV and important efforts have been performed during the first outbreak to develop diagnostic tools. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. For the M protein, this is the first description of production in plants, while for plant-derived N protein we demonstrate that it is recognized by sera of patients from the SARS outbreak in Hong Kong in 2003. The availability of recombinant N and M proteins from plants opens the way to further evaluation of their potential utility for the development of diagnostic and protection/therapy tools to be quickly manufactured, at low cost and with minimal risk, to face potential new highly infectious SARS-CoV outbreaks. PMID:26904039

  5. Antigen Production in Plant to Tackle Infectious Diseases Flare Up: the Case of SARS

    Directory of Open Access Journals (Sweden)

    Olivia C eDemurtas

    2016-02-01

    Full Text Available Severe Acute Respiratory Syndrome (SARS is a dangerous infection with pandemic potential. It emerged in 2002 and its aetiological agent, the SARS Coronavirus (SARS-CoV, crossed the species barrier to infect humans, showing high morbidity and mortality rates. No vaccines are currently licensed for SARS-CoV and important efforts have been performed during the first outbreak to develop diagnostic tools. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N and the membrane protein (M using a virus-derived vector or agro-infiltration, respectively. For the M protein, this is the first description of production in plants, while for plant-derived N protein we demonstrate that it is recognized by sera of patients from the SARS outbreak in Hong Kong in 2003. The availability of recombinant N and M proteins from plants opens the way to further evaluation of their potential utility for the development of diagnostic and protection/therapy tools to be quickly manufactured, at low cost and with minimal risk, to face potential new highly infectious SARS-CoV outbreaks.

  6. UAVSAR and TerraSAR-X Based InSAR Detection of Localized Subsidence in the New Orleans Area

    Science.gov (United States)

    Blom, R. G.; An, K.; Jones, C. E.; Latini, D.

    2014-12-01

    Vulnerability of the US Gulf coast to inundation has received increased attention since hurricanes Katrina and Rita. Compounding effects of sea level rise, wetland loss, and regional and local subsidence makes flood protection a difficult challenge, and particularly for the New Orleans area. Key to flood protection is precise knowledge of elevations and elevation changes. Analysis of historical and continuing geodetic measurements show surprising complexity, including locations subsiding more rapidly than considered during planning of hurricane protection and coastal restoration projects. Combining traditional, precise geodetic data with interferometric synthetic aperture radar (InSAR) observations can provide geographically dense constraints on surface deformation. The Gulf Coast environment is challenging for InSAR techniques, especially with systems not designed for interferometry. We use two InSAR capable systems, the L- band (24 cm wavelength) airborne JPL/NASA UAVSAR, and the DLR/EADS Astrium spaceborne TerraSAR X-band (3 cm wavelength), and compare results. First, we are applying pair-wise InSAR to the longer wavelength UAVSAR data to detect localized elevation changes potentially impacting flood protection infrastructure from 2009 - 2014. We focus on areas on and near flood protection infrastructure to identify changes indicative of subsidence, structural deformation, and/or seepage. The Spaceborne TerraSAR X-band SAR system has relatively frequent observations, and dense persistent scatterers in urban areas, enabling measurement of very small displacements. We compare L-band UAVSAR results with permanent scatterer (PS-InSAR) and Short Baseline Subsets (SBAS) interferometric analyses of a stack composed by 28 TerraSAR X-band images acquired over the same period. Thus we can evaluate results from the different radar frequencies and analyses techniques. Preliminary results indicate subsidence features potentially of a variety of causes, including ground water

  7. Signal subspace change detection in averaged multi-look SAR imagery

    Science.gov (United States)

    Ranney, Kenneth; Soumekh, Mehrdad

    2005-05-01

    Modern Synthetic Aperture Radar (SAR) signal processing algorithms could retrieve accurate and subtle information regarding a scene that is being interrogated by an airborne radar system. An important reconnaissance problem that is being studied via the use of SAR systems and their sophisticated signal processing methods involves detecting changes in an imaged scene. In these problems, the user interrogates a scene with a SAR system at two different time points (e.g. different days); the resultant two SAR databases that we refer to as reference and test data, are used to determine where targets have entered or left the imaged scene between the two data acquisitions. For instance, X band SAR systems have the potential to become a potent tool to determine whether mines have been recently placed in an area. This paper describes an algorithm for detecting changes in averaged multi-look SAR imagery. Averaged multi-look SAR images are preferable to full aperture SAR reconstructions when the imaging algorithm is approximation based (e.g. polar format processing), or motion data are not accurate over a long full aperture. We study the application of a SAR detection method, known as Signal Subspace Processing, that is based on the principles of 2D adaptive filtering. We identify the change detection problem as a binary hypothesis-testing problem, and identify an error signal and its normalized version to determine whether i) there is no change in the imaged scene; or ii) a target has been added to the imaged scene. A statistical analysis of the error signal is provided to show its properties and merits. Results are provided for data collected by an X band SAR platform and processed to form non-coherently look-averaged SAR images.

  8. The SARS coronavirus nucleocapsid protein--forms and functions.

    Science.gov (United States)

    Chang, Chung-ke; Hou, Ming-Hon; Chang, Chi-Fon; Hsiao, Chwan-Deng; Huang, Tai-huang

    2014-03-01

    The nucleocapsid phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV N protein) packages the viral genome into a helical ribonucleocapsid (RNP) and plays a fundamental role during viral self-assembly. It is a protein with multifarious activities. In this article we will review our current understanding of the N protein structure and its interaction with nucleic acid. Highlights of the progresses include uncovering the modular organization, determining the structures of the structural domains, realizing the roles of protein disorder in protein-protein and protein-nucleic acid interactions, and visualizing the ribonucleoprotein (RNP) structure inside the virions. It was also demonstrated that N-protein binds to nucleic acid at multiple sites with a coupled-allostery manner. We propose a SARS-CoV RNP model that conforms to existing data and bears resemblance to the existing RNP structures of RNA viruses. The model highlights the critical role of modular organization and intrinsic disorder of the N protein in the formation and functions of the dynamic RNP capsid in RNA viruses. This paper forms part of a symposium in Antiviral Research on "From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses." Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Identifying Candidate Targets of Immune Responses in Zika Virus Based on Homology to Epitopes in Other Flavivirus Species

    OpenAIRE

    Xu, Xiaojun; Vaughan, Kerrie; Weiskopf, Daniela; Grifoni, Alba; Diamond, Michael S.; Sette, Alessandro; Peters, Bjoern

    2016-01-01

    Introduction: The current outbreak of Zika virus has resulted in a massive effort to accelerate the development of ZIKV-specific diagnostics and vaccines. These efforts would benefit greatly from the definition of the specific epitope targets of immune responses in ZIKV, but given the relatively recent emergence of ZIKV as a pandemic threat, few such data are available. Methods: We used a large body of epitope data for other Flaviviruses that was available from the IEDB for a comparative anal...

  10. Geodetic imaging of tectonic deformation with InSAR

    Science.gov (United States)

    Fattahi, Heresh

    Precise measurements of ground deformation across the plate boundaries are crucial observations to evaluate the location of strain localization and to understand the pattern of strain accumulation at depth. Such information can be used to evaluate the possible location and magnitude of future earthquakes. Interferometric Synthetic Aperture Radar (InSAR) potentially can deliver small-scale (few mm/yr) ground displacement over long distances (hundreds of kilometers) across the plate boundaries and over continents. However, Given the ground displacement as our signal of interest, the InSAR observations of ground deformation are usually affected by several sources of systematic and random noises. In this dissertation I identify several sources of systematic and random noise, develop new methods to model and mitigate the systematic noise and to evaluate the uncertainty of the ground displacement measured with InSAR. I use the developed approach to characterize the tectonic deformation and evaluate the rate of strain accumulation along the Chaman fault system, the western boundary of the India with Eurasia tectonic plates. I evaluate the bias due to the topographic residuals in the InSAR range-change time-series and develope a new method to estimate the topographic residuals and mitigate the effect from the InSAR range-change time-series (Chapter 2). I develop a new method to evaluate the uncertainty of the InSAR velocity field due to the uncertainty of the satellite orbits (Chapter 3) and a new algorithm to automatically detect and correct the phase unwrapping errors in a dense network of interferograms (Chapter 4). I develop a new approach to evaluate the impact of systematic and stochastic components of the tropospheric delay on the InSAR displacement time-series and its uncertainty (Chapter 5). Using the new InSAR time-series approach developed in the previous chapters, I study the tectonic deformation across the western boundary of the India plate with Eurasia and

  11. Novel Alphacoronaviruses and Paramyxoviruses Cocirculate with Type 1 and Severe Acute Respiratory System (SARS)-Related Betacoronaviruses in Synanthropic Bats of Luxembourg.

    Science.gov (United States)

    Pauly, Maude; Pir, Jacques B; Loesch, Catherine; Sausy, Aurélie; Snoeck, Chantal J; Hübschen, Judith M; Muller, Claude P

    2017-09-15

    Several infectious disease outbreaks with high mortality in humans have been attributed to viruses that are thought to have evolved from bat viruses. In this study from Luxembourg, the genetic diversity and epidemiology of paramyxoviruses and coronaviruses shed by the bat species Rhinolophus ferrumequinum and Myotis emarginatus were evaluated. Feces collection ( n = 624) was performed longitudinally in a mixed-species colony in 2015 and 2016. In addition, feces ( n = 254) were collected cross-sectionally from six Myotis emarginatus colonies in 2016. By use of degenerate primers in a nested format, overall prevalences of 1.1% (10/878) and 4.9% (43/878) were determined for paramyxoviruses and coronaviruses. Sequences of the partial RNA-dependent RNA polymerase and spike glycoprotein genes of coronaviruses, as well as sequences of the partial L gene of paramyxoviruses, were obtained. Novel paramyxovirus and Alphacoronavirus strains were identified in different Myotis emarginatus colonies, and severe acute respiratory syndrome (SARS)-related Betacoronavirus strains were shed by Rhinolophus ferrumequinum Logistic regression revealed that the level of Alphacoronavirus shedding was highest in July (odds ratio, 2.8; P < 0.01), probably due to periparturient stress. Phylogenetic analyses point to close virus-host coevolution, and the high genetic similarity of the study strains suggests that the Myotis emarginatus colonies in Luxembourg are socially connected. Most interestingly, we show that bats also host Betacoronavirus 1 strains. The high similarity of the spike gene sequences of these viruses with mammalian Betacoronavirus 1 strains may be of concern. Both the SARS-related and Betacoronavirus 1 strains detected in bats in Luxembourg may cross the species barrier after a host adaptation process. IMPORTANCE Bats are a natural reservoir of a number of zoonotic pathogens. Several severe outbreaks in humans (e.g., a Nipah virus outbreak in Malaysia in 1998, and the almost

  12. Accelerated Scientific InSAR Processing Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Neva Ridge Technologies proposes to develop a suite of software tools for the analysis of SAR and InSAR data, focused on having a robust and adopted capability well...

  13. SAR Image Enhancement using Particle Filters

    Data.gov (United States)

    National Aeronautics and Space Administration — In this paper, we propose a novel approach to reduce the noise in Synthetic Aperture Radar (SAR) images using particle filters. Interpretation of SAR images is a...

  14. Polarimetric and Interferometric SAR Calibration Verification Methods

    Science.gov (United States)

    Kim, Y.; Zyl, J van

    2001-01-01

    It is necessary to calibrate SAR data in order to use the data for science applications. When both polarimetric and interferometric data are collected simultaneously, these SAR data can be used for cross-calibration and verification.

  15. Novel Polarimetric SAR Interferometry Algorithms Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Polarimetric radar interferometry (PolInSAR) is a new SAR imaging mode that is rapidly becoming an important technique for bare earth topographic mapping, tree...

  16. SAR Tomography Based on Block Compressive Sensing

    National Research Council Canada - National Science Library

    Wang Aichun; Xiang Maosheng

    2016-01-01

    While the use of SAR Tomography (TomoSAR) based on Compressive Sensing (CS) makes it possible to reconstruct the height profile of an observed scene, the performance of the reconstruction decreases for a structural observed scene...

  17. SAR matrices: automated extraction of information-rich SAR tables from large compound data sets.

    Science.gov (United States)

    Wassermann, Anne Mai; Haebel, Peter; Weskamp, Nils; Bajorath, Jürgen

    2012-07-23

    We introduce the SAR matrix data structure that is designed to elucidate SAR patterns produced by groups of structurally related active compounds, which are extracted from large data sets. SAR matrices are systematically generated and sorted on the basis of SAR information content. Matrix generation is computationally efficient and enables processing of large compound sets. The matrix format is reminiscent of SAR tables, and SAR patterns revealed by different categories of matrices are easily interpretable. The structural organization underlying matrix formation is more flexible than standard R-group decomposition schemes. Hence, the resulting matrices capture SAR information in a comprehensive manner.

  18. SARS among Critical Care Nurses, Toronto

    OpenAIRE

    Loeb, Mark; McGeer, Allison; Henry, Bonnie; Ofner, Marianna; Rose, David; Hlywka, Tammy; Levie, Joanne; McQueen, Jane; Smith, Stephanie; Moss, Lorraine; Smith, Andrew; Green, Karen; Walter, Stephen D.

    2004-01-01

    To determine factors that predispose or protect healthcare workers from severe acute respiratory syndrome (SARS), we conducted a retrospective cohort study among 43 nurses who worked in two Toronto critical care units with SARS patients. Eight of 32 nurses who entered a SARS patient’s room were infected. The probability of SARS infection was 6% per shift worked. Assisting during intubation, suctioning before intubation, and manipulating the oxygen mask were high-risk activities. Consistently ...

  19. Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus

    Directory of Open Access Journals (Sweden)

    Weber Friedemann

    2006-03-01

    Full Text Available Abstract Background SARS coronavirus (SARS-CoV is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV. Results A comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293. Conclusion Our data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.

  20. Generation of human antibody fragments recognizing distinct epitopes of the nucleocapsid (N SARS-CoV protein using a phage display approach

    Directory of Open Access Journals (Sweden)

    Grasso Felicia

    2005-09-01

    Full Text Available Abstract Background Severe acute respiratory syndrome (SARS-CoV is a newly emerging virus that causes SARS with high mortality rate in infected people. Successful control of the global SARS epidemic will require rapid and sensitive diagnostic tests to monitor its spread, as well as, the development of vaccines and new antiviral compounds including neutralizing antibodies that effectively prevent or treat this disease. Methods The human synthetic single-chain fragment variable (scFv ETH-2 phage antibody library was used for the isolation of scFvs against the nucleocapsid (N protein of SARS-CoV using a bio panning-based strategy. The selected scFvs were characterized under genetics-molecular aspects and for SARS-CoV N protein detection in ELISA, western blotting and immunocytochemistry. Results Human scFv antibodies to N protein of SARS-CoV can be easily isolated by selecting the ETH-2 phage library on immunotubes coated with antigen. These in vitro selected human scFvs specifically recognize in ELISA and western blotting studies distinct epitopes in N protein domains and detect in immunohistochemistry investigations SARS-CoV particles in infected Vero cells. Conclusion The human scFv antibodies isolated and described in this study represent useful reagents for rapid detection of N SARS-CoV protein and SARS virus particles in infected target cells.

  1. Live Cell Analysis and Mathematical Modeling Identify Determinants of Attenuation of Dengue Virus 2'-O-Methylation Mutant.

    Directory of Open Access Journals (Sweden)

    Bianca Schmid

    2015-12-01

    Full Text Available Dengue virus (DENV is the most common mosquito-transmitted virus infecting ~390 million people worldwide. In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available. DENV elicits a strong interferon (IFN response in infected cells, but at the same time actively counteracts IFN production and signaling. Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems. To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes. We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic. Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN. By contrast, a vaccine candidate DENV mutant, which lacks 2'-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells. Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production. This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate. In contrast, accelerated protection of naïve cells by paracrine IFN action has negligible impact. In conclusion, these results show that attenuation of the 2'-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells.

  2. Convolutional Neural Networks for SAR Image Segmentation

    DEFF Research Database (Denmark)

    Malmgren-Hansen, David; Nobel-Jørgensen, Morten

    2015-01-01

    Segmentation of Synthetic Aperture Radar (SAR) images has several uses, but it is a difficult task due to a number of properties related to SAR images. In this article we show how Convolutional Neural Networks (CNNs) can easily be trained for SAR image segmentation with good results. Besides...

  3. SAR Systems and Related Signal Processing

    NARCIS (Netherlands)

    Hoogeboom, P.; Dekker, R.J.; Otten, M.P.G.

    1996-01-01

    Synthetic Aperture Radar (SAR) is today a valuable source of remote sensing information. SAR is a side-looking imaging radar and operates from airborne and spacebome platforms. Coverage, resolution and image quality are strongly influenced by the platform. SAR processing can be performed on standard

  4. Squint mode SAR processing algorithms

    Science.gov (United States)

    Chang, C. Y.; Jin, M.; Curlander, J. C.

    1989-01-01

    The unique characteristics of a spaceborne SAR (synthetic aperture radar) operating in a squint mode include large range walk and large variation in the Doppler centroid as a function of range. A pointing control technique to reduce the Doppler drift and a new processing algorithm to accommodate large range walk are presented. Simulations of the new algorithm for squint angles up to 20 deg and look angles up to 44 deg for the Earth Observing System (Eos) L-band SAR configuration demonstrate that it is capable of maintaining the resolution broadening within 20 percent and the ISLR within a fraction of a decibel of the theoretical value.

  5. High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

    Science.gov (United States)

    2010-06-01

    viruses . N-glycosylation of viral envelopes is an important such target shared between in- fluenza, HIV, HCV, West Nile virus , SARS-CoV, Hendra virus ...host cells. Therefore, MBL preferentially recognizes glycosylated viruses including influenza virus , human immunodeficiency virus , severe acute...are heavily glycosylated and contain high-mannose. As a result, MBL binds to Ebola and Marburg viruses and mediates com- plement-dependent virus

  6. High resolution PolInSAR with the ground-based SAR (GB-SAR) System: measurement and modelling

    OpenAIRE

    Morrison, K; Williams, M L

    2006-01-01

    Ground-based work is necessary for a comprehensive assessment of the operational potential and limitations of PolInSAR in airborne and satellite SAR applications. A study is made of the performance and usefulness of the UK’s Ground-Based SAR (GB-SAR) Outdoor System in high-resolution PolInSAR studies of vegetation using modeling results. The facility provides fully-polarimetric L- through X-band imagery down to a resolution of several wavelengths. However, the measurem...

  7. Modeling the structure of SARS 3a transmembrane protein using a ...

    Indian Academy of Sciences (India)

    3a is an accessory protein from SARS coronavirus that is known to play a significant role in the proliferation of the virus by forming tetrameric ion channels. Although the monomeric units are known to consist of three transmembrane (TM) domains, there are no solved structures available for the complete monomer.

  8. Validation of Forested Inundation Extent Revealed by L-Band Polarimetric and Interferometric SAR Data

    Science.gov (United States)

    Chapman, Bruce; Celi, Jorge; Hamilton, Steve; McDonald, Kyle

    2013-01-01

    UAVSAR, NASA's airborne Synthetic Aperture Radar (SAR), conducted an extended observational campaign in Central and South America in March 2013, primarily related to volcanic deformations along the Andean Mountain Range but also including a large number of flights studying other scientific phenomena. During this campaign, the L-Band SAR collected data over the Napo River in Ecuador. The objectives of this experiment were to acquire polarimetric and interferometric L-Band SAR data over an inundated tropical forest in Ecuador simultaneously with on-the-ground field work ascertaining the extent of inundation, and to then derive from this data a quantitative estimate for the error in the SAR-derived inundation extent. In this paper, we will first describe the processing and preliminary analysis of the SAR data. The polarimetric SAR data will be classified by land cover and inundation state. The interferometric SAR data will be used to identify those areas where change in inundation extent occurred, and to measure the change in water level between two observations separated by a week. Second, we will describe the collection of the field estimates of inundation, and have preliminary comparisons of inundation extent measured in the field field versus that estimated from the SAR data.

  9. Polarimetric scattering and SAR information retrieval

    CERN Document Server

    Jin, Ya-Qiu

    2013-01-01

    Taking an innovative look at Synthetic Aperture Radar (SAR), this practical reference fully covers new developments in SAR and its various methodologies and enables readers to interpret SAR imagery An essential reference on polarimetric Synthetic Aperture Radar (SAR), this book uses scattering theory and radiative transfer theory as a basis for its treatment of topics. It is organized to include theoretical scattering models and SAR data analysis techniques, and presents cutting-edge research on theoretical modelling of terrain surface. The book includes quantitative app

  10. Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin.

    Science.gov (United States)

    Kumaki, Yohichi; Wandersee, Miles K; Smith, Aaron J; Zhou, Yanchen; Simmons, Graham; Nelson, Nathan M; Bailey, Kevin W; Vest, Zachary G; Li, Joseph K-K; Chan, Paul Kay-Sheung; Smee, Donald F; Barnard, Dale L

    2011-04-01

    Urtica dioica agglutinin (UDA) is a small plant monomeric lectin, 8.7 kDa in size, with an N-acetylglucosamine specificity that inhibits viruses from Nidovirales in vitro. In the current study, we first examined the efficacy of UDA on the replication of different SARS-CoV strains in Vero 76 cells. UDA inhibited virus replication in a dose-dependent manner and reduced virus yields of the Urbani strain by 90% at 1.1 ± 0.4 μg/ml in Vero 76 cells. Then, UDA was tested for efficacy in a lethal SARS-CoV-infected BALB/c mouse model. BALB/c mice were infected with two LD50 (575 PFU) of virus for 4 h before the mice were treated intraperitoneally with UDA at 20, 10, 5 or 0 mg/kg/day for 4 days. Treatment with UDA at 5 mg/kg significantly protected the mice against a lethal infection with mouse-adapted SARS-CoV (p effectively reduced lung pathology scores. At day 6 after virus exposure, all groups of mice receiving UDA had much lower lung weights than did the placebo-treated mice. Thus, our data suggest that UDA treatment of SARS infection in mice leads to a substantial therapeutic effect that protects mice against death and weight loss. Furthermore, the mode of action of UDA in vitro was further investigated using live SARS-CoV Urbani strain virus and retroviral particles pseudotyped with SARS-CoV spike (S). UDA specifically inhibited the replication of live SARS-CoV or SARS-CoV pseudotyped virus when added just before, but not after, adsorption. These data suggested that UDA likely inhibits SARS-CoV infection by targeting early stages of the replication cycle, namely, adsorption or penetration. In addition, we demonstrated that UDA neutralizes the virus infectivity, presumably by binding to the SARS-CoV spike (S) glycoprotein. Finally, the target molecule for the inhibition of virus replication was partially characterized. When UDA was exposed to N-acetylglucosamine and then UDA was added to cells just prior to adsorption, UDA did not inhibit the virus infection. These

  11. Stalking SARS: CDC at Work

    Centers for Disease Control (CDC) Podcasts

    2014-05-22

    In this podcast for kids, the Kidtastics talk about the SARS outbreak and how CDC worked to solve the mystery.  Created: 5/22/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/22/2014.

  12. Signal processing for FMCW SAR

    NARCIS (Netherlands)

    Meta, A.; Hoogeboom, P.; Ligthart, L.P.

    2007-01-01

    The combination of frequency-modulated continuous-wave (FMCW) technology and synthetic aperture radar (SAR) techniques leads to lightweight cost-effective imaging sensors of high resolution. One limiting factor to the use of FMCW sensors is the well-known presence of nonlinearities in the

  13. A yeast model for the mechanism of the Epstein-Barr virus immune evasion identifies a new therapeutic target to interfere with the virus stealthiness

    Directory of Open Access Journals (Sweden)

    KaMaría José Lista

    2017-08-01

    Full Text Available The oncogenic Epstein-Barr virus (EBV evades the im-mune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome replication and maintenance but also highly antigenic. Hence, EBV evolved a system in which the glycine-alanine repeat (GAr of EBNA1 limits the translation of its own mRNA at a minimal level to ensure its essential function thereby, at the same time, minimizing immune recognition. Defining intervention points where to interfere with EBNA1 immune evasion is an important step to trigger an immune response against EBV-carrying cancers. Thanks to a yeast-based assay that recapitulates all the aspects of EBNA1 self-limitation of expression, a recent study by Lista et al. [Nature Communications (2017 7, 435-444] has un-covered the role of the host cell nucleolin (NCL in this process via a direct interaction of this protein with G-quadruplexes (G4 formed in GAr-encoding sequence of EBNA1 mRNA. In addition, the G4 ligand PhenDC3 prevents NCL binding on EBNA1 mRNA and reverses GAr-mediated repression of translation and antigen presentation. This shows that the NCL-EBNA1 mRNA interaction is a relevant therapeutic target to unveil EBV-carrying cancers to the immune system and that the yeast model can be successfully used for uncovering drugs and host factors that interfere with EBV stealthiness.

  14. Mapping Regional Inundation with Spaceborne L-Band SAR

    Directory of Open Access Journals (Sweden)

    Bruce Chapman

    2015-04-01

    Full Text Available Shortly after the launch of ALOS PALSAR L-band SAR by the Japan Space Exploration Agency (JAXA, a program to develop an Earth Science Data Record (ESDR for inundated wetlands was funded by NASA. Using established methodologies, extensive multi-temporal L-band ALOS ScanSAR data acquired bi-monthly by the PALSAR instrument onboard ALOS were used to classify the inundation state for South America for delivery as a component of this Inundated Wetlands ESDR (IW-ESDR and in collaboration with JAXA’s ALOS Kyoto and Carbon Initiative science programme. We describe these methodologies and the final classification of the inundation state, then compared this with results derived from dual-season data acquired by the JERS-1 L-band SAR mission in 1995 and 1996, as well as with estimates of surface water extent measured globally every 10 days by coarser resolution sensors. Good correspondence was found when comparing open water extent classified from multi-temporal ALOS ScanSAR data with surface water fraction identified from coarse resolution sensors, except in those regions where there may be differences in sensitivity to widespread and shallow seasonal flooding event, or in areas that could be excluded through use of a continental-scale inundatable mask. It was found that the ALOS ScanSAR classification of inundated vegetation was relatively insensitive to inundated herbaceous vegetation. Inundation dynamics were examined using the multi-temporal ALOS ScanSAR acquisitions over the Pacaya-Samiria and surrounding areas in the Peruvian Amazon.

  15. SARS CoV main proteinase: The monomer-dimer equilibrium dissociation constant.

    Science.gov (United States)

    Graziano, Vito; McGrath, William J; Yang, Lin; Mangel, Walter F

    2006-12-12

    The SARS coronavirus main proteinase (SARS CoV main proteinase) is required for the replication of the severe acute respiratory syndrome coronavirus (SARS CoV), the virus that causes SARS. One function of the enzyme is to process viral polyproteins. The active form of the SARS CoV main proteinase is a homodimer. In the literature, estimates of the monomer-dimer equilibrium dissociation constant, KD, have varied more than 65,0000-fold, from equilibrium by three different techniques: small-angle X-ray scattering, chemical cross-linking, and enzyme kinetics. Analysis of small-angle X-ray scattering data from a series of measurements at different SARS CoV main proteinase concentrations yielded KD values of 5.8 +/- 0.8 microM (obtained from the entire scattering curve), 6.5 +/- 2.2 microM (obtained from the radii of gyration), and 6.8 +/- 1.5 microM (obtained from the forward scattering). The KD from chemical cross-linking was 12.7 +/- 1.1 microM, and from enzyme kinetics, it was 5.2 +/- 0.4 microM. While each of these three techniques can present different, potential limitations, they all yielded similar KD values.

  16. Blood donors--Serious adverse reactions (SAR) 2010-2014 EFS Châteauroux, France.

    Science.gov (United States)

    Riga, A; Sapey, T; Bacanu, M; Py, J-Y; Dehaut, F

    2015-06-01

    In 2013, the national French incidence of serious adverse reactions (SAR) was 155.7 per 100,000 donations and 82% of SAR were grade 2 (French classification of SAR related to blood donors) The purpose of our study was to describe the profile of blood donator candidate which had a SAR in our center. The study contains all the SAR superior to grade 1 occurred on the site EFS Châteauroux (site and mobile blood collection) from January 2010 to October 31, 2014. We analyzed 37 parameters from the e-fit files (e-site French blood vigilance) and In-log software. We identified 82 SAR for 72,553 blood donations (incidence: 113.02 SAR per 100,000 donations). Forty-one men and 41 women, middle age 39 years (18-66). Average height: 1.68 m (1.49-1.85); average weight: 68 kg (50-98); body mass index (kg/m(2)): 24,13(18.6-31.9). All donors were Caucasian and 30% unemployed. We found 74 vasovagal syncope (VVS), 5 hematomas, 2 arterial injuries and an adverse reaction to citrate. In 90%, the SAR was immediate and of grade 2 in 85% of cases. Thirty-seven percent of SAR were first donation in connection with whole blood in 87% of cases. Regarding the seniority of donors, the number of average donations (whole blood, plasma, platelets) was 16.5. An SAR determined the stop of blood donation in 65% of cases with nearly 80% stoppage if it was a first donation. Seventy-three percent of SAR as a VVS took place during blood collection or within 5 minutes following the end of the donation. Sixty-one percent were men. Forty-four percent of cases were a first donation and 83% occurred in mobile blood collection. Average age was 36 years. The result was a permanent stop of all type of donations in 76% of cases. Twenty-seven percent of SAR as a VVS took place beyond 5 minutes after the end of the donation. Seventy-five percent were women. Thirty percent of cases were a first donation and 95% of SAR occurred in mobile blood collection. Average age was 42 years. The result was a permanent stop of

  17. HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D

    DEFF Research Database (Denmark)

    Chentoufi, Aziz Alami; Zhang, Xiuli; Lamberth, Kasper

    2008-01-01

    epitopes identified to date. In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes. Synthetic peptides corresponding to four of these epitopes, each nine to 10...

  18. Modelling of potentially promising SARS protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)

    2007-07-18

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.

  19. An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses.

    Science.gov (United States)

    Schreiber, Claire A; Sakuma, Toshie; Izumiya, Yoshihiro; Holditch, Sara J; Hickey, Raymond D; Bressin, Robert K; Basu, Upamanyu; Koide, Kazunori; Asokan, Aravind; Ikeda, Yasuhiro

    2015-08-01

    Adeno-associated viruses (AAV) have evolved to exploit the dynamic reorganization of host cell machinery during co-infection by adenoviruses and other helper viruses. In the absence of helper viruses, host factors such as the proteasome and DNA damage response machinery have been shown to effectively inhibit AAV transduction by restricting processes ranging from nuclear entry to second-strand DNA synthesis. To identify host factors that might affect other key steps in AAV infection, we screened an siRNA library that revealed several candidate genes including the PHD finger-like domain protein 5A (PHF5A), a U2 snRNP-associated protein. Disruption of PHF5A expression selectively enhanced transgene expression from AAV by increasing transcript levels and appears to influence a step after second-strand synthesis in a serotype and cell type-independent manner. Genetic disruption of U2 snRNP and associated proteins, such as SF3B1 and U2AF1, also increased expression from AAV vector, suggesting the critical role of U2 snRNP spliceosome complex in this host-mediated restriction. Notably, adenoviral co-infection and U2 snRNP inhibition appeared to target a common pathway in increasing expression from AAV vectors. Moreover, pharmacological inhibition of U2 snRNP by meayamycin B, a potent SF3B1 inhibitor, substantially enhanced AAV vector transduction of clinically relevant cell types. Further analysis suggested that U2 snRNP proteins suppress AAV vector transgene expression through direct recognition of intact AAV capsids. In summary, we identify U2 snRNP and associated splicing factors, which are known to be affected during adenoviral infection, as novel host restriction factors that effectively limit AAV transgene expression. Concurrently, we postulate that pharmacological/genetic manipulation of components of the spliceosomal machinery might enable more effective gene transfer modalities with recombinant AAV vectors.

  20. Field validation of a commercial blocking ELISA to differentiate antibody to transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus and to identify TGEV-infected swine herds.

    Science.gov (United States)

    Carman, Susy; Josephson, Gaylan; McEwen, Beverly; Maxie, Grant; Antochi, Mioara; Eernisse, Ken; Nayar, Gopi; Halbur, Pat; Erickson, Gene; Nilsson, Ernst

    2002-03-01

    A commercially available blocking ELISA was analyzed for its ability to identify antibodies to porcine coronaviruses (transmissible gastroenteritis virus [TGEV] or porcine respiratory coronavirus [PRCV]), to differentiate antibodies to TGEV and PRCV, and to identify TGEV-infected herds. Nine sera from uninfected pigs, 34 sera from 16 pigs experimentally infected with TGEV, and sera from 10 pigs experimentally infected with PRCV were evaluated using both the TGEV/PRCV blocking ELISA and a virus neutralization (VN) assay. The ELISA was not consistently effective in identifying pigs experimentally infected with TGEV until 21 days postinfection. Sera from 100 commercial swine herds (1,783 sera; median 15 per herd) were similarly evaluated using both tests. Thirty of these commercial herds had a clinical history of TGEV infection and a positive TGEV fluorescent antibody test recorded at necropsy within the last 35 months, while 70 herds had no history of clinical TGEV infection. The blocking ELISA and the VN showed good agreement (kappa 0.84) for the detection of porcine coronavirus antibody (TGEV or PRCV). The sensitivity (0.933) of the ELISA to identify TGEV-infected herds was good when considered on a herd basis. The ELISA was also highly specific (0.943) for the detection of TGEV-infected herds when the test results were evaluated on a herd basis. When sera from specific age groups were compared, the ELISA identified a greater proportion (0.83) of pigs in herds with TGEV antibody when suckling piglets were used. In repeatability experiments, the ELISA gave consistent results when the same sera were evaluated on different days (kappa 0.889) and when sera were evaluated before and after heating (kappa 0.888). The blocking ELISA was determined to be useful for herd monitoring programs and could be used alone without parallel use of the VN assay for the assessment of large swine populations for the detection of TGEV-infected herds.

  1. Antisense downregulation of SARS-CoV gene expression in Vero E6 cells.

    Science.gov (United States)

    Shi, Yi; Luo, Haifeng; Jia, Jie; Xiong, Jie; Yang, Dehua; Huang, Bing; Jin, Youxin

    2005-01-01

    Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS-CoV). It is an enveloped, single-stranded, plus-sense RNA virus with a genome of approximately 30 kb. The structural proteins E, M and N of SARS-CoV play important roles during host cell entry and viral morphogenesis and release. Therefore, we have studied whether expression of these structural proteins can be down-regulated using an antisense technique. Vero E6 cells were transfected with plasmid constructs containing exons of the SARS-CoV structural protein E, M or N genes or their exons in frame with the reporter protein EGFP. The transfected cell cultures were treated with antisense phosphorothioated oligonucleotides (antisense PS-ODN, 20mer) or a control oligonucleotide by addition to the culture medium. Among a total of 26 antisense PS-ODNs targeting E, M and N genes, we obtained six antisense PS-ODNs which could sequence-specifically reduce target genes expression by over 90% at the concentration of 50 microM in the cell culture medium tested by RT-PCR. The antisense effect was further proved by down-regulating the expression of the fusion proteins containing the structural proteins E, M or N in frame with the reporter protein EGFP. In Vero E6 cells, the antisense effect was dependent on the concentrations of the antisense PS-ODNs in a range of 0-10 microM or 0-30 microM. The antisense PS-ODNs are effective in downregulation of SARS. The findings indicate that antisense knockdown of SARS could be a useful strategy for treatment of SARS, and could also be suitable for studies of the pathological function of SARS genes in a cellular model system.

  2. Zika Virus: the Latest Newcomer

    Science.gov (United States)

    Saiz, Juan-Carlos; Vázquez-Calvo, Ángela; Blázquez, Ana B.; Merino-Ramos, Teresa; Escribano-Romero, Estela; Martín-Acebes, Miguel A.

    2016-01-01

    Since the beginning of this century, humanity has been facing a new emerging, or re-emerging, virus threat almost every year: West Nile, Influenza A, avian flu, dengue, Chikungunya, SARS, MERS, Ebola, and now Zika, the latest newcomer. Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, was identified in 1947 in a sentinel monkey in Uganda, and later on in humans in Nigeria. The virus was mainly confined to the African continent until it was detected in south-east Asia the 1980’s, then in the Micronesia in 2007 and, more recently in the Americas in 2014, where it has displayed an explosive spread, as advised by the World Health Organization, which resulted in the infection of hundreds of thousands of people. ZIKV infection was characterized by causing a mild disease presented with fever, headache, rash, arthralgia, and conjunctivitis, with exceptional reports of an association with Guillain–Barre syndrome (GBS) and microcephaly. However, since the end of 2015, an increase in the number of GBS associated cases and an astonishing number of microcephaly in fetus and new-borns in Brazil have been related to ZIKV infection, raising serious worldwide public health concerns. Clarifying such worrisome relationships is, thus, a current unavoidable goal. Here, we extensively review what is currently known about ZIKV, from molecular biology, transmission routes, ecology, and epidemiology, to clinical manifestations, pathogenesis, diagnosis, prophylaxis, and public health. PMID:27148186

  3. Zika virus: the latest newcomer

    Directory of Open Access Journals (Sweden)

    Juan-Carlos eSaiz

    2016-04-01

    Full Text Available Since the beginning of this century, humanity has been facing a new emerging, or re-emerging, virus threat almost every year: West Nile, Influenza A, avian flu, dengue, Chikungunya, SARS, MERS, Ebola, and now Zika, the latest newcomer. Zika virus (ZIKV, a flavivirus transmitted by Aedes mosquitoes, was identified in 1947 in a sentinel monkey in Uganda, and later on in humans in Nigeria. The virus was mainly confined to the African continent until it was detected in south-east Asia the 1980´s, then in the Micronesia in 2007 and, more recently in the Americas in 2014, where it has displayed an explosive spread, as advised by the World Health Organization (WHO, which resulted in the infection of hundreds of thousands of people. ZIKV infection was characterized by causing a mild disease presented with fever, headache, rash, arthralgia, and conjunctivitis, with exceptional reports of an association with Guillain-Barre syndrome (GBS and microcephaly. However, since the end of 2015, an increase in the number of GBS associated cases and an astonishing number of microcephaly in foetus and new-borns in Brazil have been related to ZIKV infection, raising serious worldwide public health concerns. Clarifying such worrisome relationships is, thus, a current unavoidable goal. Here, we extensively review what is currently known about ZIKV, from molecular biology, transmission routes, ecology and epidemiology, to clinical manifestations, pathogenesis, diagnosis, prophylaxis and public health.

  4. Controlling Data Collection to Support SAR Image Rotation

    Science.gov (United States)

    Doerry, Armin W.; Cordaro, J. Thomas; Burns, Bryan L.

    2008-10-14

    A desired rotation of a synthetic aperture radar (SAR) image can be facilitated by adjusting a SAR data collection operation based on the desired rotation. The SAR data collected by the adjusted SAR data collection operation can be efficiently exploited to form therefrom a SAR image having the desired rotational orientation.

  5. SAR Image Complex Pixel Representations

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-01

    Complex pixel values for Synthetic Aperture Radar (SAR) images of uniform distributed clutter can be represented as either real/imaginary (also known as I/Q) values, or as Magnitude/Phase values. Generally, these component values are integers with limited number of bits. For clutter energy well below full-scale, Magnitude/Phase offers lower quantization noise than I/Q representation. Further improvement can be had with companding of the Magnitude value.

  6. Reflectors for SAR performance testing.

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2008-01-01

    Synthetic Aperture Radar (SAR) performance testing and estimation is facilitated by observing the system response to known target scene elements. Trihedral corner reflectors and other canonical targets play an important role because their Radar Cross Section (RCS) can be calculated analytically. However, reflector orientation and the proximity of the ground and mounting structures can significantly impact the accuracy and precision with which measurements can be made. These issues are examined in this report.

  7. Optimization of a Plaque Neutralization Test (PNT) to identify the exposure history of Pacific Herring to viral hemorrhagic septicemia virus (VHSV)

    Science.gov (United States)

    Hart, Lucas; Mackenzie, Ashley; Purcell, Maureen; Thompson, Rachel L.; Hershberger, Paul

    2017-01-01

    Methods for a plaque neutralization test (PNT) were optimized for the detection and quantification of viral hemorrhagic septicemia virus (VHSV) neutralizing activity in the plasma of Pacific Herring Clupea pallasii. The PNT was complement dependent, as neutralizing activity was attenuated by heat inactivation; further, neutralizing activity was mostly restored by the addition of exogenous complement from specific-pathogen-free Pacific Herring. Optimal methods included the overnight incubation of VHSV aliquots in serial dilutions (starting at 1:16) of whole test plasma containing endogenous complement. The resulting viral titers were then enumerated using a viral plaque assay in 96-well microplates. Serum neutralizing activity was virus-specific as plasma from viral hemorrhagic septicemia (VHS) survivors demonstrated only negligible reactivity to infectious hematopoietic necrosis virus, a closely related rhabdovirus. Among Pacific Herring that survived VHSV exposure, neutralizing activity was detected in the plasma as early as 37 d postexposure and peaked at approximately 64 d postexposure. The onset of neutralizing activity was slightly delayed in fish reared at 7.4°C relative to those in warmer temperatures (9.9°C and 13.1°C); however, neutralizing activity persisted for at least 345 d postexposure in all temperature treatments. It is anticipated that this novel ability to assess VHSV neutralizing activity in Pacific Herring will enable retrospective comparisons between prior VHS infections and year-class recruitment failures. Additionally, the optimized PNT could be employed as a forecasting tool capable of identifying the potential for future VHS epizootics in wild Pacific Herring populations.

  8. Genetic Characteristic and Global Transmission of Influenza A H9N2 Virus

    Directory of Open Access Journals (Sweden)

    Mingda Hu

    2017-12-01

    Full Text Available The H9N2 virus has been demonstrated to donate its genes to other subtypes of influenza A virus, forming new reassortant virus which may infect human beings. Understanding the genetic characteristic and the global transmission patterns of the virus would guide the prevention and control of potentially emerging avian influenza A virus. In this paper, we hierarchically classified the evolution of the H9N2 virus into three main lineages based on the phylogenetic characteristics of the virus. Due to the distribution of sampling locations, we named the three lineages as Worldwide lineage, Asia-Africa lineage, and China lineage. Codon usage analysis and selective positive site analysis of the lineages further showed the lineage-specific evolution of the virus. We reconstructed the transmission routes of the virus in the three lineages through phylogeography analysis, by which several epicenters for migration of the virus were identified. The hierarchical classification of the lineages implied a possible original seeding process of the virus, starting from the Worldwide lineages to the Asian-Africa lineages and to the China lineages. In the process of H9N2 virus global transmission, the United States was the origin of the virus. China Mainland, Hong Kong SAR, Japan, and Korea were important transfer centers. Based on both the transmission route and the distribution of the hosts in each lineage, we concluded that the wild birds' migration has contributed much to the long-distance global spread of the virus, while poultry trade and people's lifestyle may have contributed to the relatively short-distance transmission in some areas of the Asia and Africa.

  9. Spaceborne SAR Imaging Algorithm for Coherence Optimized.

    Directory of Open Access Journals (Sweden)

    Zhiwei Qiu

    Full Text Available This paper proposes SAR imaging algorithm with largest coherence based on the existing SAR imaging algorithm. The basic idea of SAR imaging algorithm in imaging processing is that output signal can have maximum signal-to-noise ratio (SNR by using the optimal imaging parameters. Traditional imaging algorithm can acquire the best focusing effect, but would bring the decoherence phenomenon in subsequent interference process. Algorithm proposed in this paper is that SAR echo adopts consistent imaging parameters in focusing processing. Although the SNR of the output signal is reduced slightly, their coherence is ensured greatly, and finally the interferogram with high quality is obtained. In this paper, two scenes of Envisat ASAR data in Zhangbei are employed to conduct experiment for this algorithm. Compared with the interferogram from the traditional algorithm, the results show that this algorithm is more suitable for SAR interferometry (InSAR research and application.

  10. Forest biomass estimation from polarimetric SAR interferometry

    Energy Technology Data Exchange (ETDEWEB)

    Mette, T.

    2007-07-01

    Polarimetric SAR interferometry (Pol-InSAR) is a radar remote sensing technique that allows extracting forest heights by means of model-based inversions. Forest biomass is closely related to forest height, and can be derived from it with allometric relations. This work investigates the combination of the two methods to estimate forest biomass from Pol-InSAR. It develops a concept for the use of height-biomass allometry, and outlines the Pol-InSAR height inversion. The methodology is validated against a set of forest inventory data and Pol-InSAR data at L-band of the test site Traunstein. The results allow drawing conclusions on the potential of Pol-InSAR forest biomass missions. (orig.)

  11. Ecological modeling of the spatial distribution of wild waterbirds to identify the main areas where avian influenza viruses are circulating in the Inner Niger Delta, Mali.

    Science.gov (United States)

    Cappelle, Julien; Girard, Olivier; Fofana, Bouba; Gaidet, Nicolas; Gilbert, Marius

    2010-09-01

    Predicting areas of disease emergence when no epidemiological data is available is essential for the implementation of efficient surveillance programs. The Inner Niger Delta (IND) in Mali is a major African wetland where >1 million Palearctic and African waterbirds congregate. Waterbirds are the main reservoir of Avian Influenza Viruses (AIV). Our objective was to model their spatial distribution in order to predict where these viruses would be more likely to circulate. We developed a generalized linear model (GLM) and a boosted regression trees (BRT) model based on total aerial bird counts taken in winter over 6 years. We used remotely sensed environmental variables with a high temporal resolution (10 days) to predict the spatial distribution of four waterbird groups. The predicted waterbird abundances were weighted with an epidemiological indicator based on the prevalence of low pathogenic AIV reported in the literature. The BRT model had the best predictive power and allowed prediction of the high variability of waterbird distribution. Years with low flood levels showed areas with a higher risk of circulation and had better spatial distribution predictions. Each year, the model identified a few areas with a higher risk of AIV circulation. This model can be applied every 10 days to evaluate the risk of AIV emergence in wild waterbirds. By taking into account the IND's ecological variability, it allows better targeting of areas considered for surveillance. This could enhance the control of emerging diseases at a local and regional scale, especially when resources available for surveillance programs are scarce.

  12. A site of varicella-zoster virus vulnerability identified by structural studies of neutralizing antibodies bound to the glycoprotein complex gHgL.

    Science.gov (United States)

    Xing, Yi; Oliver, Stefan L; Nguyen, TuongVi; Ciferri, Claudio; Nandi, Avishek; Hickman, Julie; Giovani, Cinzia; Yang, Edward; Palladino, Giuseppe; Grose, Charles; Uematsu, Yasushi; Lilja, Anders E; Arvin, Ann M; Carfí, Andrea

    2015-05-12

    Varicella-zoster virus (VZV), of the family Alphaherpesvirinae, causes varicella in children and young adults, potentially leading to herpes zoster later in life on reactivation from latency. The conserved herpesvirus glycoprotein gB and the heterodimer gHgL mediate virion envelope fusion with cell membranes during virus entry. Naturally occurring neutralizing antibodies against herpesviruses target these entry proteins. To determine the molecular basis for VZV neutralization, crystal structures of gHgL were determined in complex with fragments of antigen binding (Fabs) from two human monoclonal antibodies, IgG-94 and IgG-RC, isolated from seropositive subjects. These structures reveal that the antibodies target the same site, composed of residues from both gH and gL, distinct from two other neutralizing epitopes identified by negative-stain electron microscopy and mutational analysis. Inhibition of gB/gHgL-mediated membrane fusion and structural comparisons with herpesvirus homologs suggest that the IgG-RC/94 epitope is in proximity to the site on VZV gHgL that activates gB. Immunization studies proved that the anti-gHgL IgG-RC/94 epitope is a critical target for antibodies that neutralize VZV. Thus, the gHgL/Fab structures delineate a site of herpesvirus vulnerability targeted by natural immunity.

  13. Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection.

    Science.gov (United States)

    Wu, Qi; Zhou, Lina; Sun, Xin; Yan, Zhongfang; Hu, Chunxiu; Wu, Junping; Xu, Long; Li, Xue; Liu, Huiling; Yin, Peiyuan; Li, Kuan; Zhao, Jieyu; Li, Yanli; Wang, Xiaolin; Li, Yu; Zhang, Qiuyang; Xu, Guowang; Chen, Huaiyong

    2017-08-22

    Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.

  14. Exploitation of Digital Surface Models Generated from WORLDVIEW-2 Data for SAR Simulation Techniques

    Science.gov (United States)

    Ilehag, R.; Auer, S.; d'Angelo, P.

    2017-05-01

    GeoRaySAR, an automated SAR simulator developed at DLR, identifies buildings in high resolution SAR data by utilizing geometric knowledge extracted from digital surface models (DSMs). Hitherto, the simulator has utilized DSMs generated from LiDAR data from airborne sensors with pre-filtered vegetation. Discarding the need for pre-optimized model input, DSMs generated from high resolution optical data (acquired with WorldView-2) are used for the extraction of building-related SAR image parts in this work. An automatic preprocessing of the DSMs has been developed for separating buildings from elevated vegetation (trees, bushes) and reducing the noise level. Based on that, automated simulations are triggered considering the properties of real SAR images. Locations in three cities, Munich, London and Istanbul, were chosen as study areas to determine advantages and limitations related to WorldView-2 DSMs as input for GeoRaySAR. Beyond, the impact of the quality of the DSM in terms of building extraction is evaluated as well as evaluation of building DSM, a DSM only containing buildings. The results indicate that building extents can be detected with DSMs from optical satellite data with various success, dependent on the quality of the DSM as well as on the SAR imaging perspective.

  15. High-Resolution TomoSAR & PS-InSAR Analysis in Urban Areas

    Science.gov (United States)

    Wei, Lianhuan; Liao, Mingsheng; Balz, Timo; Liu, Kang; Jendryke, Michael

    2013-01-01

    The surveillance of urban infrastructures is of great importance. Urban infrastructure monitoring benefits from the launch of the new generation of high-resolution SAR satellites. With high-resolution SAR stacks, even deformation details of different building parts can be observed by PS-InSAR technique. However, high-rise building areas suffer severely from layover effects, which can cause serious phase unwrapping errors in PS-InSAR processing. SAR tomography (TomoSAR) provides a method of overcoming layover effects in urban areas. With tomographic techniques, the 3D distribution of multiple scatterers and their position can be reconstructed. In this poster, the PS-InSAR method is illustrated first, followed with PS-InSAR analysis results in Shanghai. Then, we will describe SAR tomography and why we need TomoSAR, especially in dense cities like Shanghai. Finally, preliminary tomographic results are presented. By combining PS-InSAR and TomoSAR, a 4D dynamic mapping of urban areas could be executed.

  16. Precision Rectification of Airborne SAR Image

    DEFF Research Database (Denmark)

    Dall, Jørgen; Liao, M.; Zhang, Zhe

    1997-01-01

    A simple and direct procedure for the rectification of a certain class of airborne SAR data is presented. The relief displacements of SAR data are effectively removed by means of a digital elevation model and the image is transformed to the ground coordinate system. SAR data from the Danish EMISAR......([7]) is used. The EMISAR produces data with a geometrical resolution of 2.0 meters. The corrected image is tested against photogrammetric control measurements and an accuracy better than 0.5 pixel corresponding to 0.75 meters is obtained. The results indicate promising possibilities...... for the application of SAR data in the difficult process of map revision and updating....

  17. T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV.

    Science.gov (United States)

    Liu, William J; Zhao, Min; Liu, Kefang; Xu, Kun; Wong, Gary; Tan, Wenjie; Gao, George F

    2017-01-01

    Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells

    Directory of Open Access Journals (Sweden)

    Law Helen KW

    2009-06-01

    Full Text Available Abstract Background The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs, chemokine receptors (CCRs and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB DCs to find a possible explanation for the age-dependent severity of SARS. Results Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL, but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. Conclusion The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted.

  19. Novel biomarkers of nasopharyngeal carcinoma metastasis risk identified by reverse phase protein array based tumor profiling with consideration of plasma Epstein-Barr virus DNA load.

    Science.gov (United States)

    Xu, Tao; Su, Bojin; Huang, Peiyu; Wei, Weihong; Deng, Yanming; Sehgal, Vasudha; Wang, Donghui; Jiang, Jun; Zhang, Guoyi; Li, Anfei; Yang, Huiling; Claret, Francois X

    2017-05-01

    In patients with Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC), intertumor heterogeneity causes interpatient heterogeneity in the risk of distant metastasis. We aimed to identify novel biomarkers of metastasis risk using reverse phase protein array (RPPA) profiling of NPC patients at risk for metastasis and considering plasma EBV DNA load. A total of 98 patients with NPC with and without metastasis after treatment, matched with respect to clinical parameters, are enrolled. Total protein expression is measured by RPPA, and protein functions are analyzed by pathway bioinformatics. The RPPA analysis revealed a profile of 70 proteins that are differentially expressed in metastatic and nonmetastatic tumors. Plasma EBV DNA load after treatment correlated with protein expression level better than plasma EBV DNA load before treatment did. The biomarkers of NPC metastasis identified by proteomics regulate signaling pathways involved in cell cycle progression, apoptosis, and epithelial-mesenchymal transition. The authors identified 26 biomarkers associated with 5-year distant failure-free survival in univariate analysis; five biomarkers remained significant in multivariate analysis. A comprehensive RPPA profiling study is warranted to identify novel metastasis-related biomarkers and further examine the activation state of signaling proteins to improve estimation of metastasis risk for patients with EBV-associated NPC. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Dynamics of SARS-coronavirus HR2 domain in the prefusion and transition states

    Science.gov (United States)

    McReynolds, Susanna; Jiang, Shaokai; Rong, Lijun; Caffrey, Michael

    2009-12-01

    The envelope glycoproteins S1 and S2 of severe acute respiratory syndrome coronavirus (SARS-CoV) mediate viral entry by conformational change from a prefusion state to a postfusion state that enables fusion of the viral and target membranes. In this work we present the characterization of the dynamic properties of the SARS-CoV S2-HR2 domain (residues 1141-1193 of S) in the prefusion and newly discovered transition states by NMR 15N relaxation studies. The dynamic properties of the different states, which are stabilized under different experimental conditions, extend the current model of viral membrane fusion and give insight into the design of structure-based antagonists of SARS-CoV in particular, as well as other enveloped viruses such as HIV.

  1. Robust full-length hepatitis C virus genotype 2a and 2b infectious cultures using mutations identified by a systematic approach applicable to patient strains

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Gottwein, Judith M

    2012-01-01

    Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases worldwide, but treatment options are limited. Basic HCV research required for vaccine and drug development has been hampered by inability to culture patient isolates, and to date only the JFH1 (genotype 2a) recombinant...... in vitro. Through a systematic approach of culturing J6 with minimal JFH1 sequences, we identified three mutations in NS3, NS4A, and NS5B that permitted full-length J6 propagation and adaptation with infectivity titers comparable to JFH1-based systems. The most efficient recombinant, J6cc, had six adaptive...... mutations and did not accumulate additional changes following viral passage. We demonstrated that HCV NS3/NS4A protease-, NS5A- and NS5B polymerase-directed drugs respectively inhibited full-length J6 infection dose dependently. Importantly, the three J6-derived mutations enabled culture adaptation...

  2. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.

    Science.gov (United States)

    Hu, Ben; Zeng, Lei-Ping; Yang, Xing-Lou; Ge, Xing-Yi; Zhang, Wei; Li, Bei; Xie, Jia-Zheng; Shen, Xu-Rui; Zhang, Yun-Zhi; Wang, Ning; Luo, Dong-Sheng; Zheng, Xiao-Shuang; Wang, Mei-Niang; Daszak, Peter; Wang, Lin-Fa; Cui, Jie; Shi, Zheng-Li

    2017-11-01

    A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

  3. Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants.

    Science.gov (United States)

    High, Monica; Cho, Hye-Youn; Marzec, Jacqui; Wiltshire, Tim; Verhein, Kirsten C; Caballero, Mauricio T; Acosta, Patricio L; Ciencewicki, Jonathan; McCaw, Zackary R; Kobzik, Lester; Miller-DeGraff, Laura; Gladwell, Wes; Peden, David B; Serra, M Elina; Shi, Min; Weinberg, Clarice; Suzuki, Oscar; Wang, Xuting; Bell, Douglas A; Polack, Fernando P; Kleeberger, Steven R

    2016-09-01

    Respiratory syncytial virus (RSV) is the global leading cause of lower respiratory tract infection in infants. Nearly 30% of all infected infants develop severe disease including bronchiolitis, but susceptibility mechanisms remain unclear. We infected a panel of 30 inbred strains of mice with RSV and measured changes in lung disease parameters 1 and 5days post-infection and they were used in genome-wide association (GWA) studies to identify quantitative trait loci (QTL) and susceptibility gene candidates. GWA identified QTLs for RSV disease phenotypes, and the innate immunity scavenger receptor Marco was a candidate susceptibility gene; targeted deletion of Marco worsened murine RSV disease. We characterized a human MARCO promoter SNP that caused loss of gene expression, increased in vitro cellular response to RSV infection, and associated with increased risk of disease severity in two independent populations of children infected with RSV. Translational integration of a genetic animal model and in vitro human studies identified a role for MARCO in human RSV disease severity. Because no RSV vaccines are approved for clinical use, genetic studies have implications for diagnosing individuals who are at risk for severe RSV disease, and disease prevention strategies (e.g. RSV antibodies). Published by Elsevier B.V.

  4. Serum hepatitis B core-related antigen is more accurate than hepatitis B surface antigen to identify inactive carriers, regardless of hepatitis B virus genotype.

    Science.gov (United States)

    Riveiro-Barciela, M; Bes, M; Rodríguez-Frías, F; Tabernero, D; Ruiz, A; Casillas, R; Vidal-González, J; Homs, M; Nieto, L; Sauleda, S; Esteban, R; Buti, M

    2017-11-01

    To investigate whether hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels are useful to identify inactive carriers among HBeAg-negative patients infected by different hepatitis B virus (HBV) genotypes. In all, 202 consecutive HBeAg-negative patients with chronic hepatitis B, 135 inactive carriers and 67 with HBV activity, were prospectively followed for 1 year. In HBeAg-negative patients, HBsAg levels differed across the different genotypes (p 85% in all HBV genotypes, except genotype H or F, with values of 62.5% and 72.7%, respectively, for the two parameters. HBsAg levels varied across genotypes in HBeAg-negative patients. HBsAg levels <3 logIU/mL were only useful for identifying genotype D inactive carriers. A single HBcrAg measurement ≤3 logU/mL plus HBV DNA ≤2000 IU/mL was highly accurate for identifying inactive carriers, regardless of their HBV genotype. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  5. Sentinel-3 SAR Altimetry Toolbox

    Science.gov (United States)

    Benveniste, Jerome; Lucas, Bruno; DInardo, Salvatore

    2015-04-01

    The prime objective of the SEOM (Scientific Exploitation of Operational Missions) element is to federate, support and expand the large international research community that the ERS, ENVISAT and the Envelope programmes have build up over the last 20 years for the future European operational Earth Observation missions, the Sentinels. Sentinel-3 builds directly on a proven heritage of ERS-2 and Envisat, and CryoSat-2, with a dual-frequency (Ku and C band) advanced Synthetic Aperture Radar Altimeter (SRAL) that provides measurements at a resolution of ~300m in SAR mode along track. Sentinel-3 will provide exact measurements of sea-surface height along with accurate topography measurements over sea ice, ice sheets, rivers and lakes. The first of the two Sentinels is expected to be launched in early 2015. The current universal altimetry toolbox is BRAT (Basic Radar Altimetry Toolbox) which can read all previous and current altimetry mission's data, but it does not have the capabilities to read the upcoming Sentinel-3 L1 and L2 products. ESA will endeavour to develop and supply this capability to support the users of the future Sentinel-3 SAR Altimetry Mission. BRAT is a collection of tools and tutorial documents designed to facilitate the processing of radar altimetry data. This project started in 2005 from the joint efforts of ESA (European Space Agency) and CNES (Centre National d'Etudes Spatiales), and it is freely available at http://earth.esa.int/brat. The tools enable users to interact with the most common altimetry data formats, the BratGUI is the front-end for the powerful command line tools that are part of the BRAT suite. BRAT can also be used in conjunction with Matlab/IDL (via reading routines) or in C/C++/Fortran via a programming API, allowing the user to obtain desired data, bypassing the data-formatting hassle. BRAT can be used simply to visualise data quickly, or to translate the data into other formats such as netCDF, ASCII text files, KML (Google Earth

  6. Bioinformatics analysis and characteristics of VP23 encoded by the newly identified UL18 gene of duck enteritis virus

    Science.gov (United States)

    Chen, Xiwen; Cheng, Anchun; Wang, Mingshu; Xiang, Jun

    2011-10-01

    In this study, the predicted information about structures and functions of VP23 encoded by the newly identified DEV UL18 gene through bioinformatics softwares and tools. The DEV UL18 was predicted to encode a polypeptide with 322 amino acids, termed VP23, with a putative molecular mass of 35.250 kDa and a predicted isoelectric point (PI) of 8.37, no signal peptide and transmembrane domain in the polypeptide. The prediction of subcellular localization showed that the DEV-VP23 located at endoplasmic reticulum with 33.3%, mitochondrial with 22.2%, extracellular, including cell wall with 11.1%, vesicles of secretory system with 11.1%, Golgi with 11.1%, and plasma membrane with 11.1%. The acid sequence of analysis showed that the potential antigenic epitopes are situated in 45-47, 53-60, 102-105, 173-180, 185-189, 260-265, 267-271, and 292-299 amino acids. All the consequences inevitably provide some insights for further research about the DEV-VP23 and also provide a fundament for further study on the the new type clinical diagnosis of DEV and can be used for the development of new DEV vaccine.

  7. The potential of targeted antibody prophylaxis in SARS outbreak control: a mathematic analysis.

    Science.gov (United States)

    Bogaards, Johannes Antonie; Putter, Hein; Jan Weverling, Gerrit; Ter Meulen, Jan; Goudsmit, Jaap

    2007-03-01

    Severe acute respiratory syndrome (SARS) coronavirus-like viruses continue to circulate in animal reservoirs. If new mutants of SARS coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that contained the first SARS outbreak. We developed a mathematical model to investigate the effects of hospital admission and targeted antibody prophylaxis on the reproduction number R, defined as the number of secondary cases generated by an index case, during different SARS outbreak scenarios. Assuming a basic reproduction number R(0)=3, admission of patients to hospital within 4.3 days of symptom onset is necessary to achieve outbreak control without the need to further reduce community-based transmission. Control may be enhanced by providing pre-exposure prophylaxis to contacts of hospitalized patients, and through contact tracing and provision of post-exposure prophylaxis. Antibody prophylaxis may also be employed to reduce R below one and thereby restrict outbreak size and duration. Patient isolation alone can be sufficient to control SARS outbreaks provided that the time from onset to admission is short. Antibody prophylaxis as supplemental measure generally allows for containment of higher R(0) values and restricts both the size and duration of an outbreak.

  8. 16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment

    Science.gov (United States)

    Guerrero-Preston, Rafael; Godoy-Vitorino, Filipa; Jedlicka, Anne; Rodríguez-Hilario, Arnold; González, Herminio; Bondy, Jessica; Lawson, Fahcina; Folawiyo, Oluwasina; Michailidi, Christina; Dziedzic, Amanda; Thangavel, Rajagowthamee; Hadar, Tal; Noordhuis, Maartje G.; Westra, William; Koch, Wayne; Sidransky, David

    2016-01-01

    Systemic inflammatory events and localized disease, mediated by the microbiome, may be measured in saliva as head and neck squamous cell carcinoma (HNSCC) diagnostic and prognostic biomonitors. We used a 16S rRNA V3-V5 marker gene approach to compare the saliva microbiome in DNA isolated from Oropharyngeal (OPSCC), Oral Cavity Squamous Cell Carcinoma (OCSCC) patients and normal epithelium controls, to characterize the HNSCC saliva microbiota and examine their abundance before and after surgical resection. The analyses identified a predominance of Firmicutes, Proteobacteria and Bacteroidetes, with less frequent presence of Actinobacteria and Fusobacteria before surgery. At lower taxonomic levels, the most abundant genera were Streptococcus, Prevotella, Haemophilus, Lactobacillus and Veillonella, with lower numbers of Citrobacter and Neisseraceae genus Kingella. HNSCC patients had a significant loss in richness and diversity of microbiota species (p<0.05) compared to the controls. Overall, the Operational Taxonomic Units network shows that the relative abundance of OTU's within genus Streptococcus, Dialister, and Veillonella can be used to discriminate tumor from control samples (p<0.05). Tumor samples lost Neisseria, Aggregatibacter (Proteobacteria), Haemophillus (Firmicutes) and Leptotrichia (Fusobacteria). Paired taxa within family Enterobacteriaceae, together with genus Oribacterium, distinguish OCSCC samples from OPSCC and normal samples (p<0.05). Similarly, only HPV positive samples have an abundance of genus Gemellaceae and Leuconostoc (p<0.05). Longitudinal analyses of samples taken before and after surgery, revealed a reduction in the alpha diversity measure after surgery, together with an increase of this measure in patients that recurred (p<0.05). These results suggest that microbiota may be used as HNSCC diagnostic and prognostic biomonitors. PMID:27259999

  9. SAR/MTI on small airborne platforms

    NARCIS (Netherlands)

    Rossum, W.L. van; Vermeulen, B.C.B.

    2006-01-01

    A small SAR-MTI system is being developed at TNO, aimed at deployment on tactical UAV. The system makes use of modern front-end technology, to provide flexible SAR imaging and MTI modes. Major design goals are 50 kg weight, 500 W power consumption and 50 cm resolution in order to comply with typical

  10. A Simple Model for a SARS Epidemic

    Science.gov (United States)

    Ang, Keng Cheng

    2004-01-01

    In this paper, we examine the use of an ordinary differential equation in modelling the SARS outbreak in Singapore. The model provides an excellent example of using mathematics in a real life situation. The mathematical concepts involved are accessible to students with A level Mathematics backgrounds. Data for the SARS epidemic in Singapore are…

  11. SAR change detection techniques and applications

    NARCIS (Netherlands)

    Dekker, R.J.

    2005-01-01

    ABSTRACT: Change detection, the comparison of remote sensing images from different moments in time, is an important technique in environmental earth observation and security. SAR change detection is useful when weather and light conditions are unfavourable. Five methods of SAR change detection are

  12. Geologic mapping in Greenland with polarimetric SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Madsen, Søren Nørvang; Brooks, C. K.

    1995-01-01

    The application of synthetic aperture radar (SAR) for geologic mapping in Greenland is investigated by the Danish Center for Remote Sensing (DCRS) in co-operation with the Danish Lithosphere Centre (DLC). In 1994 a pilot project was conducted in East Greenland. The Danish airborne SAR, EMISAR...

  13. Real-time brute force SAR processing

    NARCIS (Netherlands)

    Vlothuizen, W.J.; Ditzel, M.

    2009-01-01

    This paper presents a brute force method to perform real-time SAR processing. The method has several advantages over traditional so-called fast SAR implementations, as it does not make any approximations to alleviate the processing burden. However, the method does allow efficient implementation on

  14. Characterizing forest stands with multi-incidence angle and multi-polarized SAR data

    Science.gov (United States)

    Hoffer, R. M.; Lozano-Garcia, D. F.; Gillespie, D. D.

    1987-01-01

    The potential for using HH-polarized L-band SAR data obtained at different incidence angles from satellite altitudes to identify and map different forest cover types and stand density classes is studied. Reasonably accurate results are obtained if the speckle characteristics of the data are suppressed by low-pass spatial filters and a contextual classification algorithm. Multipolarized L-band SAR data obtained from aircraft altitudes over the same test site are also analyzed to assess the relationships between polarization and forest stand characteristics. It is found that incidence angle controls, to a very large extent, the characteristics of the data and the type of information that can be obtained from L-band, HH-polarized satellite SAR data. Cross-polarization of L-band SAR data enhances and differentiates various forest stand characteristics which cannot be defined using only the like-polarized data, and vice-versa.

  15. Development of animal models against emerging coronaviruses: From SARS to MERS coronavirus.

    Science.gov (United States)

    Sutton, Troy C; Subbarao, Kanta

    2015-05-01

    Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV. Copyright © 2015. Published by Elsevier Inc.

  16. Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine.

    Science.gov (United States)

    Jimenez-Guardeño, Jose M; Regla-Nava, Jose A; Nieto-Torres, Jose L; DeDiego, Marta L; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Perlman, Stanley; Enjuanes, Luis

    2015-10-01

    A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV.

  17. Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine

    Science.gov (United States)

    Nieto-Torres, Jose L.; DeDiego, Marta L.; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Perlman, Stanley; Enjuanes, Luis

    2015-01-01

    A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV. PMID:26513244

  18. Deep learning for SAR image formation

    Science.gov (United States)

    Mason, Eric; Yonel, Bariscan; Yazici, Birsen

    2017-04-01

    The recent success of deep learning has lead to growing interest in applying these methods to signal processing problems. This paper explores the applications of deep learning to synthetic aperture radar (SAR) image formation. We review deep learning from a perspective relevant to SAR image formation. Our objective is to address SAR image formation in the presence of uncertainties in the SAR forward model. We present a recurrent auto-encoder network architecture based on the iterative shrinkage thresholding algorithm (ISTA) that incorporates SAR modeling. We then present an off-line training method using stochastic gradient descent and discuss the challenges and key steps of learning. Lastly, we show experimentally that our method can be used to form focused images in the presence of phase uncertainties. We demonstrate that the resulting algorithm has faster convergence and decreased reconstruction error than that of ISTA.

  19. Geometric calibration of ERS satellite SAR images

    DEFF Research Database (Denmark)

    Mohr, Johan Jacob; Madsen, Søren Nørvang

    2001-01-01

    Geometric calibration of the European Remote Sensing (ERS) Satellite synthetic aperture radar (SAR) slant range images is important in relation to mapping areas without ground reference points and also in relation to automated processing. The relevant SAR system parameters are discussed and calib......Geometric calibration of the European Remote Sensing (ERS) Satellite synthetic aperture radar (SAR) slant range images is important in relation to mapping areas without ground reference points and also in relation to automated processing. The relevant SAR system parameters are discussed...... on a seven-year ERS-1 and a four-year ERS-2 time series, the long term stability is found to be sufficient to allow a single calibration covering the entire mission period. A descending and an ascending orbit tandem pair of the ESA calibration site on Flevoland, suitable for calibration of ERS SAR processors...

  20. Composite SAR imaging using sequential joint sparsity

    Science.gov (United States)

    Sanders, Toby; Gelb, Anne; Platte, Rodrigo B.

    2017-06-01

    This paper investigates accurate and efficient ℓ1 regularization methods for generating synthetic aperture radar (SAR) images. Although ℓ1 regularization algorithms are already employed in SAR imaging, practical and efficient implementation in terms of real time imaging remain a challenge. Here we demonstrate that fast numerical operators can be used to robustly implement ℓ1 regularization methods that are as or more efficient than traditional approaches such as back projection, while providing superior image quality. In particular, we develop a sequential joint sparsity model for composite SAR imaging which naturally combines the joint sparsity methodology with composite SAR. Our technique, which can be implemented using standard, fractional, or higher order total variation regularization, is able to reduce the effects of speckle and other noisy artifacts with little additional computational cost. Finally we show that generalizing total variation regularization to non-integer and higher orders provides improved flexibility and robustness for SAR imaging.

  1. Pixel Classification of SAR ice images using ANFIS-PSO Classifier

    Directory of Open Access Journals (Sweden)

    G. Vasumathi

    2016-12-01

    Full Text Available Synthetic Aperture Radar (SAR is playing a vital role in taking extremely high resolution radar images. It is greatly used to monitor the ice covered ocean regions. Sea monitoring is important for various purposes which includes global climate systems and ship navigation. Classification on the ice infested area gives important features which will be further useful for various monitoring process around the ice regions. Main objective of this paper is to classify the SAR ice image that helps in identifying the regions around the ice infested areas. In this paper three stages are considered in classification of SAR ice images. It starts with preprocessing in which the speckled SAR ice images are denoised using various speckle removal filters; comparison is made on all these filters to find the best filter in speckle removal. Second stage includes segmentation in which different regions are segmented using K-means and watershed segmentation algorithms; comparison is made between these two algorithms to find the best in segmenting SAR ice images. The last stage includes pixel based classification which identifies and classifies the segmented regions using various supervised learning classifiers. The algorithms includes Back propagation neural networks (BPN, Fuzzy Classifier, Adaptive Neuro Fuzzy Inference Classifier (ANFIS classifier and proposed ANFIS with Particle Swarm Optimization (PSO classifier; comparison is made on all these classifiers to propose which classifier is best suitable for classifying the SAR ice image. Various evaluation metrics are performed separately at all these three stages.

  2. Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines.

    Science.gov (United States)

    Müller, Marcel A; Raj, V Stalin; Muth, Doreen; Meyer, Benjamin; Kallies, Stephan; Smits, Saskia L; Wollny, Robert; Bestebroer, Theo M; Specht, Sabine; Suliman, Tasnim; Zimmermann, Katrin; Binger, Tabea; Eckerle, Isabella; Tschapka, Marco; Zaki, Ali M; Osterhaus, Albert D M E; Fouchier, Ron A M; Haagmans, Bart L; Drosten, Christian

    2012-12-11

    A new human coronavirus (hCoV-EMC) has emerged very recently in the Middle East. The clinical presentation resembled that of the severe acute respiratory syndrome (SARS) as encountered during the epidemic in 2002/2003. In both cases, acute renal failure was observed in humans. HCoV-EMC is a member of the same virus genus as SARS-CoV but constitutes a sister species. Here we investigated whether it might utilize angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Knowledge of the receptor is highly critical because the restriction of the SARS receptor to deep compartments of the human respiratory tract limited the spread of SARS. In baby hamster kidney (BHK) cells, lentiviral transduction of human ACE2 (hACE2) conferred permissiveness and replication for SARS-CoV but not for hCoV-EMC. Monkey and human kidney cells (LLC-MK2, Vero, and 769-P) and swine kidney cells were permissive for both viruses, but only SARS-CoV infection could be blocked by anti-hACE2 antibody and could be neutralized by preincubation of virus with soluble ACE2. Our data show that ACE2 is neither necessary nor sufficient for hCoV-EMC replication. Moreover, hCoV-EMC, but not SARS-CoV, replicated in cell lines from Rousettus, Rhinolophus, Pipistrellus, Myotis, and Carollia bats, representing four major chiropteran families from both suborders. As human CoV normally cannot replicate in bat cells from different families, this suggests that hCoV-EMC might use a receptor molecule that is conserved in bats, pigs, and humans, implicating a low barrier against cross-host transmission. IMPORTANCE A new human coronavirus (hCoV) emerged recently in the Middle East. The disease resembled SARS (severe acute respiratory syndrome), causing a fatal epidemic in 2002/2003. Coronaviruses have a reservoir in bats and because this novel virus is related to SARS-CoV, we investigated whether it might replicate in bat cells and use the same receptor (angiotensin-converting enzyme 2 [ACE2]). This knowledge is

  3. SAR Surface Ice Cover Discrimination Using Distribution Matching

    Science.gov (United States)

    Gill, R. S.

    2003-04-01

    Discrimination between open water and sea ice in SAR imagery can still pose a problem to the ice analysts during manual interpretation. To help them in this task, new algorithm have been tested which is based on the user first manually identifying a particular surface type in a SAR image (e.g., open water area or sea ice of particular concentration or ice type) then the program will automatically determine similar regions in the remainder of an image. The algorithm is based on matching the statistics of the known and unknown regions using either (a) Kolmogorov-Smirnov (KS), or (b) Chi- Square (CS) distribution matching test. The main advantage in using these distribution matching tests is that the knowledge of the probability distribution functions (pdf) of the regions are not needed. Both KS and CS tests determine whether the two data sets belong to the same or different, yet undetermined, distributions. The main difference between KS and CS tests is that they are valid for un-binned and binned data respectively. The KS and CS were tested on the amplitude SAR image and the image products: (a) Power-to-Mean Ratio (PMR), and (b) Gamma-pdf which are computed from it. Both PMR and Gamma-pdf are useful tools for discriminating between open water and sea ice type in SAR images. The results presented in this article shows that the KS test is efficient (both reliable and computationally fast) at identifying similar surface types. It performed best with the amplitude data and Gamma-pdf while results using the PMR images were more prone to ambiguities. CS test did not perform as well as the KS test. This is because the data first has to be arbitrarily binned which results in some information being inevitably lost. It was also found to be many times slower to run on the computer. For these reasons it was decided not to use the CS test for matching known and unknown regions in a SAR image. The information obtained using the KS tests can be considered as the 'best statistical

  4. Sequence Variation in a Newly Identified HLA-B35-Restricted Epitope in the Influenza A Virus Nucleoprotein Associated with Escape from Cytotoxic T Lymphocytes

    Science.gov (United States)

    Boon, A. C. M.; de Mutsert, G.; Graus, Y. M. F.; Fouchier, R. A. M.; Sintnicolaas, K.; Osterhaus, A. D. M. E.; Rimmelzwaan, G. F.

    2002-01-01

    Here, we describe a new HLA-B*3501-restricted cytotoxic T lymphocyte (CTL) epitope in the influenza A virus (H3N2) nucleoprotein, which was found to exhibit a high degree of variation at nonanchor residues. The influenza virus variants emerged in chronological order, and CTLs directed against old variants failed to recognize more recent strains of influenza A virus, indicating an escape from CTL immunity. PMID:11836437

  5. Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay.

    Science.gov (United States)

    Elshabrawy, Hatem A; Fan, Jilao; Haddad, Christine S; Ratia, Kiira; Broder, Christopher C; Caffrey, Michael; Prabhakar, Bellur S

    2014-04-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) and Ebola, Hendra, and Nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. These viruses depend on cathepsin L for entry into their target cells. The viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. In this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoproteins of the aforementioned viruses, which contain the cathepsin L cleavage site. We screened a library of 5,000 small molecules and discovered a small molecule that can inhibit the cathepsin L cleavage of all viral peptides with minimal inhibition of cleavage of a host protein-derived peptide (pro-neuropeptide Y). The small molecule inhibited the entry of all pseudotyped viruses in vitro and the cleavage of SARS-CoV spike glycoprotein in an in vitro cleavage assay. In addition, the Hendra and Nipah virus fusion glycoproteins were not cleaved in the presence of the small molecule in a cell-based cleavage assay. Furthermore, we demonstrate that the small molecule is a mixed inhibitor of cathepsin L. Our broad-spectrum antiviral small molecule appears to be an ideal candidate for future optimization and development into a potent antiviral against SARS-CoV and Ebola, Hendra, and Nipah viruses. We developed a novel high-throughput screening assay to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins derived from SARS-CoV and Ebola, Hendra, and Nipah viruses that are required for their entry into the host cell. We identified a novel broad-spectrum small molecule that could block cathepsin L-mediated cleavage and thus inhibit the entry of pseudotypes bearing the glycoprotein derived from SARS-CoV or Ebola, Hendra, or Nipah virus. The small molecule can be further optimized and developed into a potent broad-spectrum antiviral drug.

  6. Multiple alignment analysis on phylogenetic tree of the spread of SARS epidemic using distance method

    Science.gov (United States)

    Amiroch, S.; Pradana, M. S.; Irawan, M. I.; Mukhlash, I.

    2017-09-01

    Multiple Alignment (MA) is a particularly important tool for studying the viral genome and determine the evolutionary process of the specific virus. Application of MA in the case of the spread of the Severe acute respiratory syndrome (SARS) epidemic is an interesting thing because this virus epidemic a few years ago spread so quickly that medical attention in many countries. Although there has been a lot of software to process multiple sequences, but the use of pairwise alignment to process MA is very important to consider. In previous research, the alignment between the sequences to process MA algorithm, Super Pairwise Alignment, but in this study used a dynamic programming algorithm Needleman wunchs simulated in Matlab. From the analysis of MA obtained and stable region and unstable which indicates the position where the mutation occurs, the system network topology that produced the phylogenetic tree of the SARS epidemic distance method, and system area networks mutation.

  7. Validation of burst overlapping for ALOS-2 PALSAR-2 ScanSAR-ScanSAR interferometry

    Science.gov (United States)

    Natsuaki, Ryo; Motohka, Takeshi; Ohki, Masato; Watanabe, Manabu; Suzuki, Shinichi

    2016-10-01

    The Phased Array type L-band Synthetic Aperture Radar-2 (PALSAR-2) aboard the Advanced Land Observing Satellite- 2 (ALOS-2, "DAICHI-2") is the latest L-band spaceborne synthetic aperture radar (SAR). PALSAR-2 observes the world mainly with 10 m resolution / 70 km swath Stripmap mode and 25 m resolution / 350 km swath ScanSAR mode. The 3-m resolution Stripmap mode is mainly used upon Japan. 350 km ScanSAR observation could detect large scale deformation e.g., the Mw 7.8 Gorkha, Nepal earthquake and its aftershocks in 2015. ALOS-2 ScanSAR is the first one that supports ScanSAR-ScanSAR interferometry in L-band spaceborne SAR. However, because of the parameter setting error for the orbit estimation, ALOS-2 PALSAR-2 ScanSAR could achieve little number of interferometric pair until the software modification on February 8, 2015. That is, the burst overlap timing required for the interferometric analysis was insufficient and it depends on the observation date. In this paper, we report the investigation results of this case and discuss the current status of the ALOS-2 ScanSAR InSAR. Some archives achieved before February 8, 2015 can be used for interferometric analysis with after Feb. 8. However, most of them have no interferometric pair. We also report that the archives acquired after February 8, have enough burst overlapping.

  8. High Resolution TomoSAR & PS-InSAR Analysis in Urban Areas

    Science.gov (United States)

    Wei, Lianhuan; Liao, Mingsheng; Balz, Timo; Liu, Kang; Jendryke, Michael

    2013-01-01

    The surveillance of urban infrastructures is of great importance. Urban infrastructure monitoring benefits from the launch of the new generation of high-resolution SAR satellites. With high-resolution SAR stacks, even deformation details of different building parts can be observed. The PS-InSAR technique has become a favorable tool for urban area subsidence monitoring, and it has been demonstrated that millimeter accuracy can be achieved. However, high-rise building areas suffer severely from layover effects, which can cause serious phase unwrapping errors. SAR tomography provides a method of overcoming layover effects in urban areas. With tomographic techniques, the 3D distribution of multiple scatterers and their position can be reconstructed. In this paper, the PS-InSAR method is briefly described first, followed by PS-InSAR analysis results in Shanghai. Then, we will describe SAR tomography and why we need TomoSAR, especially in dense cities like Shanghai. Finally, preliminary tomographic results about Shanghai are presented. By combining PS-InSAR and TomoSAR, a 4D dynamic mapping of urban areas could be executed.

  9. Deformation Detection of Potential Landslide with InSAR Observation

    Science.gov (United States)

    Liu, Yuzhou; Liao, Mingsheng; Shi, Xuguo; Zhang, Lu

    2016-08-01

    Influenced by geological and climate conditions, Guide County has been identified as a landslide prone area. Multi-temporal InSAR technique can implement continuous earth surface deformation detection with long time scale and wide geography coverage. In this research, we employ the SBAS method to survey potential landslide in Guide County. Two anomalous deformation regions have been detected by L-band PALSAR stacks. Preliminary correlation between the time series deformation and triggering factors is analyzed to explore the driving mechanism for landslide movement. As a consequence, L-band SAR has a good application potential in landslide monitoring and the results can be the basis for landslide recognizing and early warning.

  10. Comparative Proteomic Analysis of Wild-Type and SAP Domain Mutant Foot-and-Mouth Disease Virus-Infected Porcine Cells Identifies the Ubiquitin-Activating Enzyme UBE1 Required for Virus Replication.

    Science.gov (United States)

    Zhu, Zixiang; Yang, Fan; Zhang, Keshan; Cao, Weijun; Jin, Ye; Wang, Guoqing; Mao, Ruoqing; Li, Dan; Guo, Jianhong; Liu, Xiangtao; Zheng, Haixue

    2015-10-02

    Leader protein (L(pro)) of foot-and-mouth disease virus (FMDV) manipulates the activities of several host proteins to promote viral replication and pathogenicity. L(pro) has a conserved protein domain SAP that is suggested to subvert interferon (IFN) production to block antiviral responses. However, apart from blocking IFN production, the roles of the SAP domain during FMDV infection in host cells remain unknown. Therefore, we identified host proteins associated with the SAP domain of L(pro) by a high-throughput quantitative proteomic approach [isobaric tags for relative and absolute quantitation (iTRAQ) in conjunction with liquid chromatography/electrospray ionization tandem mass spectrometry]. Comparison of the differentially regulated proteins in rA/FMDVΔmSAP- versus rA/FMDV-infected SK6 cells revealed 45 down-regulated and 32 up-regulated proteins that were mostly associated with metabolic, ribosome, spliceosome, and ubiquitin-proteasome pathways. The results also imply that the SAP domain has a function similar to SAF-A/B besides its potential protein inhibitor of activated signal transducer and activator of transcription (PIAS) function. One of the identified proteins UBE1 was further analyzed and displayed a novel role for the SAP domain of L(pro). Overexpression of UBE1 enhanced the replication of FMDV, and knockdown of UBE1 decreased FMDV replication. This shows that FMDV manipulates UBE1 for increased viral replication, and the SAP domain was involved in this process.

  11. Large-scale sequence analysis of hemagglutinin of influenza A virus identifies conserved regions suitable for targeting an anti-viral response.

    Science.gov (United States)

    Sahini, Leepakshi; Tempczyk-Russell, Anna; Agarwal, Ritu

    2010-02-17

    Influenza A viral surface protein, hemagglutinin, is the major target of neutralizing antibody response and hence a main constituent of all vaccine formulations. But due to its marked evolutionary variability, vaccines have to be reformulated so as to include the hemagglutinin protein from the emerging new viral strain. With the constant fear of a pandemic, there is critical need for the development of anti-viral strategies that can provide wider protection against any Influenza A pathogen. An anti-viral approach that is directed against the conserved regions of the hemaggutinin protein has a potential to protect against any current and new Influenza A virus and provide a solution to this ever-present threat to public health. Influenza A human hemagglutinin protein sequences available in the NCBI database, corresponding to H1, H2, H3 and H5 subtypes, were used to identify highly invariable regions of the protein. Nine such regions were identified and analyzed for structural properties like surface exposure, hydrophilicity and residue type to evaluate their suitability for targeting an anti-peptide antibody/anti-viral response. This study has identified nine conserved regions in the hemagglutinin protein, five of which have the structural characteristics suitable for an anti-viral/anti-peptide response. This is a critical step in the design of efficient anti-peptide antibodies as novel anti-viral agents against any Influenza A pathogen. In addition, these anti-peptide antibodies will provide broadly cross-reactive immunological reagents and aid the rapid development of vaccines against new and emerging Influenza A strains.

  12. CFAR Edge Detector for Polarimetric SAR Images

    DEFF Research Database (Denmark)

    Schou, Jesper; Skriver, Henning; Nielsen, Allan Aasbjerg

    2003-01-01

    Finding the edges between different regions in an image is one of the fundamental steps of image analysis, and several edge detectors suitable for the special statistics of synthetic aperture radar (SAR) intensity images have previously been developed. In this paper, a new edge detector for polar......Finding the edges between different regions in an image is one of the fundamental steps of image analysis, and several edge detectors suitable for the special statistics of synthetic aperture radar (SAR) intensity images have previously been developed. In this paper, a new edge detector...... for polarimetric SAR images is presented using a newly developed test statistic in the complex Wishart distribution to test for equality of covariance matrices. The new edge detector can be applied to a wide range of SAR data from single-channel intensity data to multifrequency and/or multitemporal polarimetric...... SAR data. By simply changing the parameters characterizing the test statistic according to the applied SAR data, constant false-alarm rate detection is always obtained. An adaptive filtering scheme is presented, and the distributions of the detector are verified using simulated polarimetric SAR images...

  13. Sea surface slicks measured by SAR

    Energy Technology Data Exchange (ETDEWEB)

    Trivero, P. [Alessandria Univ. del Piemonte Orientale, Alessandri (Italy). Dipt. di Scienze e Tecnologie Avanzate; Fiscella, B. [Turin Univ., Turin (Italy). Dipt. di Fisica Generale; Pavese, P. [Consiglio Nazionale delle Ricerche, Istituto di Cosmogeofisica, Turin (Italy)

    2001-02-01

    The Synthetic Aperture Radar (SAR) system capability to detect and characterize marine surface slicks was tested during the SAR-580 experiment in the northern Adriatic Sea, offshore the Venice coast, in October 1990. Two small artificial slicks of oleyl alcohol were produced in an area around the oceanographic platform of the Italian National Research Council (CNR). The oleyl alcohol produces a damping of the sea centimetric waves, which has been measured by an airborne two band (C and X) SAR, by a tower based 3 band (L, S and C) scatterometer and by a wave gauge, installed on board the platform, which measures the instantaneous sea surface elevation in the range form gravity up to capillary waves. The good agreement among measures proves that multi-frequency SAR is able to detect and characterized sea surface films. Slicks in SAR images taken during SIR-C/X-SAR mission in 1994 have been analysed on the basis of these results and L-band measurements of spatial attenuation near the borders of the slicks have been done, in order to test the slicks detectability using single-band SAR images.

  14. Middle East respiratory syndrome coronavirus (MERS-CoV): challenges in identifying its source and controlling its spread.

    Science.gov (United States)

    Lu, Lu; Liu, Qi; Du, Lanying; Jiang, Shibo

    2013-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV), a novel human coronavirus that caused outbreaks of a SARS-like illness in the Middle East, is now considered a threat to global public health. This review discusses the challenges in identifying the source of this fatal virus and developing effective and safe anti-MERS-CoV vaccines and therapeutics in order to control its spread and to combat any future pandemic. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  15. Rapid Flood Map Generation from Spaceborne SAR Observations

    Science.gov (United States)

    Yun, S. H.; Liang, C.; Manipon, G.; Jung, J.; Gurrola, E. M.; Owen, S. E.; Hua, H.; Agram, P. S.; Webb, F.; Sacco, G. F.; Rosen, P. A.; Simons, M.

    2016-12-01

    The Advanced Rapid Imaging and Analysis (ARIA) team has responded to the January 2016 US Midwest Floods along the Mississippi River. Daily teleconferences with FEMA, NOAA, NGA, and USGS, provided information on precipitation and flood crest migration, based on which we coordinated with the Japanese Aerospace Exploration Agency (JAXA) through NASA headquarters for JAXA's ALOS-2 timely tasking over two paths. We produced flood extent maps using ALOS-2 SM3 mode Level 1.5 data that were provided through the International Charter and stored at the US Geological Survey's Hazards Data Distribution System (HDDS) archive. On January 6, the first four frames (70 km x 240 km) were acquired, which included the City of Memphis. We registered post-event SAR images to pre-event images, applied radiometric calibration, took a logarithm of the ratio of the two images. Two thresholds were applied to represent flooded areas that became open water (colored in blue) and flooded areas with tall vegetation (colored in red). The second path was acquired on January 11 further down along the Mississippi River. Seven frames (70 km x 420 km) were acquired and flood maps were created in the similar fashion. The maps were delivered to the FEMA as well as posted on ARIA's public website. The FEMA stated that SAR provides inspection priority for optical imagery and ground response. The ALOS-2 data and the products have been a very important source of information during this response as the flood crest has moved down stream. The SAR data continue to be an important resource during times when optical observations are often not useful. In close collaboration with FEMA and USGS, we also work on other flood events including June 2016 China Floods using European Space Agency's (ESA's) Sentienl-1 data, to produce flood extent maps and identify algorithmic needs and ARIA system's requirements to automate and rapidly produce and deliver flood maps for future events. With the addition of Sentinel-1B

  16. Manejo del virus de la hoja amarilla (sugarcane yellow leaf virus, scylv) de la caña de azúcar (saccharum officinarum) mediante cultivo de tejidos y el uso de agentes inductores de resistencia sistémica adquirida, sar

    OpenAIRE

    Burbano, C.; Garces, F.

    2009-01-01

    La presente investigación busca alternativas para el manejo del virus de la hoja amarilla de la caña de azúcar (SCYLV) tanto para la obtención de semilla libres del virus y su posterior manejo para reducir las reinfecciones en campo a causa del áfido blanco (Melanaphis sacchari Zehnt); vector del virus. Para el efecto se planteó la aplicación de herramientas de cultivo de tejidos como son la extracción de meristemos, inducción de callos embriogénicos y la utilización del viricida Ribavirín; a...

  17. Complex surface deformation of Akutan volcano, Alaska revealed from InSAR time series

    Science.gov (United States)

    Wang, Teng; DeGrandpre, Kimberly; Lu, Zhong; Freymueller, Jeffrey T.

    2018-02-01

    Akutan volcano is one of the most active volcanoes in the Aleutian arc. An intense swarm of volcano-tectonic earthquakes occurred across the island in 1996. Surface deformation after the 1996 earthquake sequence has been studied using Interferometric Synthetic Aperture Radar (InSAR), yet it is hard to determine the detailed temporal behavior and spatial extent of the deformation due to decorrelation and the sparse temporal sampling of SAR data. Atmospheric delay anomalies over Akutan volcano are also strong, bringing additional technical challenges. Here we present a time series InSAR analysis from 2003 to 2016 to reveal the surface deformation in more detail. Four tracks of Envisat data acquired from 2003 to 2010 and one track of TerraSAR-X data acquired from 2010 to 2016 are processed to produce high-resolution surface deformation, with a focus on studying two transient episodes of inflation in 2008 and 2014. For the TerraSAR-X data, the atmospheric delay is estimated and removed using the common-master stacking method. These derived deformation maps show a consistently uplifting area on the northeastern flank of the volcano. From the TerraSAR-X data, we quantify the velocity of the subsidence inside the caldera to be as high as 10 mm/year, and identify another subsidence area near the ground cracks created during the 1996 swarm.

  18. Symptom combinations associated with outcome and therapeutic effects in a cohort of cases with SARS.

    Science.gov (United States)

    Li, Shao; Wang, Ruiqin; Zhang, Yulong; Zhang, Xuegong; Layon, A Joseph; Li, Yanda; Chen, Mingzhe

    2006-01-01

    Severe acute respiratory syndrome (SARS) is an infectious disease and some of its symptoms were clinically indistinguishable of those from similar diseases. This study aimed to find the symptom combinations associated with adverse outcome and the therapeutic effects in a cohort of patients with probable SARS retrospectively. In 2003, 123 SARS cases in Beijing were subjected to a strictly western medicine (WM) treatment, or a combined treatment (WM plus Herba houttuyniae injection, addition of individualized herbal treatments when necessary), of which 115 were followed till death or discharge; 8 were transferred and lost to follow-up. In both treatment groups, clinical manifestations were evaluated daily; development of signs and symptoms, and their possible relationship with outcome, were assessed. The relationships between these sign/symptom complexes and outcome under two treatment protocols were evaluated and differences were noted. Dynamic symptom combinations, dividing into the early, the medium-term and the durational symptom clusters, were identified as likely being related to the adverse outcomes of SARS (p arterial oxyhemoglobin saturation significantly at day 22 (p < 0.05). In conclusion, the progress and outcome of SARS may be associated with specific temporal patterns of development in combination of several non-specific signs and symptom complexes, which are also helpful for evaluating the therapeutic effects on SARS patients.

  19. European Surveillance Network for Influenza in Pigs: Surveillance Programs, Diagnostic Tools and Swine Influenza Virus Subtypes Identified in 14 European Countries from 2010 to 2013

    DEFF Research Database (Denmark)

    Simon, Gaelle; Larsen, Lars Erik; Duerrwald, Ralf

    2014-01-01

    Swine influenza causes concern for global veterinary and public health officials. In continuing two previous networks that initiated the surveillance of swine influenza viruses (SIVs) circulating in European pigs between 2001 and 2008, a third European Surveillance Network for Influenza in Pigs......, mainly conducted through passive surveillance programs, resulted in the examination of more than 9 000 herds in 17 countries. Influenza A viruses were detected in 31% of herds examined from which 1887 viruses were preliminary characterized. The dominating subtypes were the three European enzootic SIVs......: avian-like swine H1N1 (53.6%), human-like reassortant swine H1N2 (13%) and human-like reassortant swine H3N2 (9.1%), as well as pandemic A/H1N1 2009 (H1N1pdm) virus (10.3%). Viruses from these four lineages co-circulated in several countries but with very different relative levels of incidence...

  20. An Open Receptor-Binding Cavity of Hemagglutinin-Esterase-Fusion Glycoprotein from Newly-Identified Influenza D Virus: Basis for Its Broad Cell Tropism.

    Directory of Open Access Journals (Sweden)

    Hao Song

    2016-01-01

    Full Text Available Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, a new influenza D virus (IDV was isolated from pigs and cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for virus entry. Then, we determined the crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF of IDV both in its free form and in complex with the receptor and enzymatic substrate analogs. The IDV HEF shows an extremely similar structural fold as the human-infecting influenza C virus (ICV HEF. However, IDV HEF has an open receptor-binding cavity to accommodate diverse extended glycan moieties. This structural difference provides an explanation for the phenomenon that the IDV has a broad cell tropism. As IDV HEF is structurally and functionally similar to ICV HEF, our findings highlight the potential threat of the virus to public health.

  1. Certainties and Uncertainties Facing Emerging Respiratory Infectious Diseases: Lessons from SARS

    Directory of Open Access Journals (Sweden)

    Yee-Chun Chen

    2008-06-01

    Full Text Available Every emerging infectious disease is a challenge to the whole of mankind. There are uncertainties regarding whether there will be a pandemic, if it will be caused by the highly pathogenic H5N1 influenza virus, when or where it will occur, how imminent or how severe it will be. No one can accurately predict if and when a given virus will become a pandemic virus. Pandemic prevention strategies must be based on preparing for the unexpected and being capable of reacting accordingly. There is growing evidence that infection control measures were helpful in containment of severe acute respiratory syndrome (SARS as well as avian influenza. Compliance of standard infection control measures, intensive promotion of hand and respiratory hygiene, vigilance and triage of patients with febrile illness, and specific infection control measures are key components to contain a highly contagious disease in hospital and to protect healthcare workers, patients and visitors. The importance of standard precautions for any patient and cleaning and disinfection for the healthcare environment cannot be overemphasized. SARS illustrated dramatically the potential of air travel and globalization for the dissemination of an emerging infectious disease. To prevent the potential serious consequences of pandemic influenza, timely implementation of pharmaceutical and non-pharmaceutical interventions locally within the outbreak area is the key to minimizing global spread. Herein, we relate our perspective on useful lessons derived from a review of the SARS epidemic that may be useful to physicians, especially when looking ahead to the next epidemic.

  2. Land Subsidence Monitoring Using PS-InSAR Technique for L-Band SAR Data

    Science.gov (United States)

    Thapa, S.; Chatterjee, R. S.; Singh, K. B.; Kumar, D.

    2016-10-01

    Differential SAR-Interferometry (D-InSAR) is one of the potential source to measure land surface motion induced due to underground coal mining. However, this technique has many limitation such as atmospheric in homogeneities, spatial de-correlation, and temporal decorrelation. Persistent Scatterer Interferometry synthetic aperture radar (PS-InSAR) belongs to a family of time series InSAR technique, which utilizes the properties of some of the stable natural and anthropogenic targets which remain coherent over long time period. In this study PS-InSAR technique has been used to monitor land subsidence over selected location of Jharia Coal field which has been correlated with the ground levelling measurement. This time series deformation observed using PS InSAR helped us to understand the nature of the ground surface deformation due to underground mining activity.

  3. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Anna de Lang

    2007-08-01

    Full Text Available The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.

  4. Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13.

    Science.gov (United States)

    Yu, Mi-Sun; Lee, June; Lee, Jin Moo; Kim, Younggyu; Chin, Young-Won; Jee, Jun-Goo; Keum, Young-Sam; Jeong, Yong-Joo

    2012-06-15

    Severe acute respiratory syndrome (SARS) is an infectious disease with a strong potential for transmission upon close personal contact and is caused by the SARS-coronavirus (CoV). However, there are no natural or synthetic compounds currently available that can inhibit SARS-CoV. We examined the inhibitory effects of 64 purified natural compounds against the activity of SARS helicase, nsP13, and the hepatitis C virus (HCV) helicase, NS3h, by conducting fluorescence resonance energy transfer (FRET)-based double-strand (ds) DNA unwinding assay or by using a colorimetry-based ATP hydrolysis assay. While none of the compounds, examined in our study inhibited the DNA unwinding activity or ATPase activity of human HCV helicase protein, we found that myricetin and scutellarein potently inhibit the SARS-CoV helicase protein in vitro by affecting the ATPase activity, but not the unwinding activity, nsP13. In addition, we observed that myricetin and scutellarein did not exhibit cytotoxicity against normal breast epithelial MCF10A cells. Our study demonstrates for the first time that selected naturally-occurring flavonoids, including myricetin and scultellarein might serve as SARS-CoV chemical inhibitors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. SARS-CoV ORF1b-encoded nonstructural proteins 12-16: replicative enzymes as antiviral targets.

    Science.gov (United States)

    Subissi, Lorenzo; Imbert, Isabelle; Ferron, François; Collet, Axelle; Coutard, Bruno; Decroly, Etienne; Canard, Bruno

    2014-01-01

    The SARS (severe acute respiratory syndrome) pandemic caused ten years ago by the SARS-coronavirus (SARS-CoV) has stimulated a number of studies on the molecular biology of coronaviruses. This research has provided significant new insight into many mechanisms used by the coronavirus replication-transcription complex (RTC). The RTC directs and coordinates processes in order to replicate and transcribe the coronavirus genome, a single-stranded, positive-sense RNA of outstanding length (∼27-32kilobases). Here, we review the up-to-date knowledge on SARS-CoV replicative enzymes encoded in the ORF1b, i.e., the main RNA-dependent RNA polymerase (nsp12), the helicase/triphosphatase (nsp13), two unusual ribonucleases (nsp14, nsp15) and RNA-cap methyltransferases (nsp14, nsp16). We also review how these enzymes co-operate with other viral co-factors (nsp7, nsp8, and nsp10) to regulate their activity. These last ten years of research on SARS-CoV have considerably contributed to unravel structural and functional details of one of the most fascinating replication/transcription machineries of the RNA virus world. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses". Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Wave directional spectrum from SAR imagery

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, A.A.; Sarma, Y.V.B.; Menon, H.B.; Vethamony, P.

    and surface wind waves, especially swell. SAR is also useful for ship detection Ocean waves are weakly 10 A.A. Fernandes et al. imaged and can be recognized from SAR imagery from their fine "finger print" like signature. In contrast with ocean waves.../internal waves by all types of radar including ship radar, Real Aperture Radar (RAR) mounted on aeroplanes and Synthetic. Aperture Radar (SAR) mounted on satellites, is by modulation of the back-scatter from short Bragg resonant capillary-gravity waves...

  7. Offshore wind mapping Mediterranean area using SAR

    DEFF Research Database (Denmark)

    Calaudi, Rosamaria; Arena, Felice; Badger, Merete

    2013-01-01

    Satellite observations of the ocean surface, for example from Synthetic Aperture Radars (SAR), provide information about the spatial wind variability over large areas. This is of special interest in the Mediterranean Sea, where spatial wind information is only provided by sparse buoys, often...... with long periods of missing data. Here, we focus on evaluating the use of SAR for offshore wind mapping. Preliminary results from the analysis of SAR-based ocean winds in Mediterranean areas show interesting large scale wind flow features consistent with results from previous studies using numerical models...

  8. NASA/JPL Aircraft SAR Workshop Proceedings

    Science.gov (United States)

    Donovan, N. (Editor); Evans, D. L. (Editor); Held, D. N. (Editor)

    1985-01-01

    Speaker-supplied summaries of the talks given at the NASA/JPL Aircraft SAR Workshop on February 4 and 5, 1985, are provided. These talks dealt mostly with composite quadpolarization imagery from a geologic or ecologic prespective. An overview and summary of the system characteristics of the L-band synthetic aperture radar (SAR) flown on the NASA CV-990 aircraft are included as supplementary information. Other topics ranging from phase imagery and interferometric techniques classifications of specific areas, and the potentials and limitations of SAR imagery in various applications are discussed.

  9. SAR ATR Based on Convolutional Neural Network

    Directory of Open Access Journals (Sweden)

    Tian Zhuangzhuang

    2016-06-01

    Full Text Available This study presents a new method of Synthetic Aperture Radar (SAR image target recognition based on a convolutional neural network. First, we introduce a class separability measure into the cost function to improve this network’s ability to distinguish between categories. Then, we extract SAR image features using the improved convolutional neural network and classify these features using a support vector machine. Experimental results using moving and stationary target acquisition and recognition SAR datasets prove the validity of this method.

  10. Pharmacophore modeling, resistant mutant isolation, docking, and MM-PBSA analysis: Combined experimental/computer-assisted approaches to identify new inhibitors of the bovine viral diarrhea virus (BVDV).

    Science.gov (United States)

    Tonelli, Michele; Boido, Vito; La Colla, Paolo; Loddo, Roberta; Posocco, Paola; Paneni, Maria Silvia; Fermeglia, Maurizio; Pricl, Sabrina

    2010-03-15

    Starting from a series of our new 2-phenylbenzimidazole derivatives, shown to be selectively and potently active against the bovine viral diarrhea virus (BVDV), we developed a hierarchical combined experimental/molecular modeling strategy to explore the drug leads for the BVDV RNA-dependent RNA-polymerase. Accordingly, a successful 3D pharmacophore model was developed, characterized by distinct chemical features that may be responsible for the activity of the inhibitors. BVDV mutants resistant to lead compounds in our series were then isolated, and the mutant residues on the viral molecular target, the RNA-dependent RNA-polymerase, were identified. Docking procedures upon pharmacophoric constraints and mutational data were carried out, and the binding affinity of all active compounds for the RdRp were estimated. Given the excellent agreement between in silico and in vitro data, this procedure is currently being employed in the design a new series of more selective and potent BVDV inhibitors. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Exploiting drug-resistant enzymes as tools to identify thienopyrimidinone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H.

    Science.gov (United States)

    Masaoka, Takashi; Chung, Suhman; Caboni, Pierluigi; Rausch, Jason W; Wilson, Jennifer A; Taskent-Sezgin, Humeyra; Beutler, John A; Tocco, Graziella; Le Grice, Stuart F J

    2013-07-11

    The thienopyrimidinone 5,6-dimethyl-2-(4-nitrophenyl)thieno[2,3-d]pyrimidin-4(3H)-one (DNTP) occupies the interface between the p66 ribonuclease H (RNase H) domain and p51 thumb of human immunodeficiency virus reverse transcriptase (HIV RT), thereby inducing a conformational change incompatible with catalysis. Here, we combined biochemical characterization of 39 DNTP derivatives with antiviral testing of selected compounds. In addition to wild-type HIV-1 RT, derivatives were evaluated with rationally designed, p66/p51 heterodimers exhibiting high-level DNTP sensitivity or resistance. This strategy identified 3',4'-dihydroxyphenyl (catechol) substituted thienopyrimidinones with submicromolar in vitro activity against both wild type HIV-1 RT and drug-resistant variants. Thermal shift analysis indicates that, in contrast to active site RNase H inhibitors, these thienopyrimidinones destabilize the enzyme, in some instances reducing the Tm by 5 °C. Importantly, catechol-containing thienopyrimidinones also inhibit HIV-1 replication in cells. Our data strengthen the case for allosteric inhibition of HIV RNase H activity, providing a platform for designing improved antagonists for use in combination antiviral therapy.

  12. Use of the International Classification of Diseases, 9th revision, coding in identifying chronic hepatitis B virus infection in health system data: implications for national surveillance.

    Science.gov (United States)

    Mahajan, Reena; Moorman, Anne C; Liu, Stephen J; Rupp, Loralee; Klevens, R Monina

    2013-05-01

    With increasing use electronic health records (EHR) in the USA, we looked at the predictive values of the International Classification of Diseases, 9th revision (ICD-9) coding system for surveillance of chronic hepatitis B virus (HBV) infection. The chronic HBV cohort from the Chronic Hepatitis Cohort Study was created based on electronic health records (EHR) of adult patients who accessed services from 2006 to 2008 from four healthcare systems in the USA. Using the gold standard of abstractor review to confirm HBV cases, we calculated the sensitivity, specificity, positive and negative predictive values using one qualifying ICD-9 code versus using two qualifying ICD-9 codes separated by 6 months or greater. Of 1 652 055 adult patients, 2202 (0.1%) were confirmed as having chronic HBV. Use of one ICD-9 code had a sensitivity of 83.9%, positive predictive value of 61.0%, and specificity and negative predictive values greater than 99%. Use of two hepatitis B-specific ICD-9 codes resulted in a sensitivity of 58.4% and a positive predictive value of 89.9%. Use of one or two hepatitis B ICD-9 codes can identify cases with chronic HBV infection with varying sensitivity and positive predictive values. As the USA increases the use of EHR, surveillance using ICD-9 codes may be reliable to determine the burden of chronic HBV infection and would be useful to improve reporting by state and local health departments.

  13. Virus-induced gene silencing identifies Catharanthus roseus 7-deoxyloganic acid-7-hydroxylase, a step in iridoid and monoterpene indole alkaloid biosynthesis.

    Science.gov (United States)

    Salim, Vonny; Yu, Fang; Altarejos, Joaquín; De Luca, Vincenzo

    2013-12-01

    Iridoids are a major group of biologically active molecules that are present in thousands of plant species, and one versatile iridoid, secologanin, is a precursor for the assembly of thousands of monoterpenoid indole alkaloids (MIAs) as well as a number of quinoline alkaloids. This study uses bioinformatics to screen large databases of annotated transcripts from various MIA-producing plant species to select candidate genes that may be involved in iridoid biosynthesis. Virus-induced gene silencing of the selected genes combined with metabolite analyses of silenced plants was then used to identify the 7-deoxyloganic acid 7-hydroxylase (CrDL7H) that is involved in the 3rd to last step in secologanin biosynthesis. Silencing of CrDL7H reduced secologanin levels by at least 70%, and increased the levels of 7-deoxyloganic acid to over 4 mg g(-1) fresh leaf weight compared to control plants in which this iridoid is not detected. Functional expression of this CrDL7H in yeast confirmed its biochemical activity, and substrate specificity studies showed its preference for 7-deoxyloganic acid over other closely related substrates. Together, these results suggest that hydroxylation precedes carboxy-O-methylation in the secologanin pathway in Catharanthus roseus. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  14. Message concerning Severe Acute Respiratory Syndrome ("SARS")

    CERN Multimedia

    2003-01-01

    IMPORTANT REMINDER If you have just come back from one of the regions identified by the WHO as being infected with SARS, it is essential to monitor your state of health for ten days after your return. The syndrome manifests itself in the rapid onset of a high fever combined with respiratory problems (coughing, breathlessness, breathing difficulty). Should these signs appear, you must contact the CERN Medical Service as quickly as possible on number 73802 or 73186 during normal working hours, and the fire brigade at all other times on number 74444, indicating that you have just returned from one of the WHO-identified areas with recent local transmission.China: Beijing, Hong Kong (Special Administrative Region), Guangdong Province, Inner Mongolia, Shanxi Province, Tianjin ProvinceTaiwan:TaipeiMoreover, until further notice the CERN Management requests that all trips to these various regions of the world be reduced to a strict minimum and then only with the consent of the Division Leader concerned. Anyone comin...

  15. Differential sensitivity of bat cells to infection by enveloped RNA viruses: coronaviruses, paramyxoviruses, filoviruses, and influenza viruses.

    Directory of Open Access Journals (Sweden)

    Markus Hoffmann

    Full Text Available Bats (Chiroptera host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat or Yangochiroptera (genera Carollia and Tadarida for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV, a porcine coronavirus, or to infection mediated by the Spike (S protein of SARS-coronavirus (SARS-CoV incorporated into pseudotypes based on vesicular stomatitis virus (VSV. The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3 were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed.

  16. A Rapid Screening Assay Identifies Monotherapy with Interferon-ß and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus.

    Directory of Open Access Journals (Sweden)

    Stephen D S McCarthy

    2016-01-01

    Full Text Available To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD. While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies, differences in experimental methodologies make it difficult to compare their therapeutic effectiveness. Using an in vitro model of Ebola Zaire replication with transcription-competent virus like particles (trVLPs, requiring only level 2 biosafety containment, we compared the activities of the type I interferons (IFNs IFN-α and IFN-ß, a panel of viral polymerase inhibitors (lamivudine (3TC, zidovudine (AZT tenofovir (TFV, favipiravir (FPV, the active metabolite of brincidofovir, cidofovir (CDF, and the estrogen receptor modulator, toremifene (TOR, in inhibiting viral replication in dose-response and time course studies. We also tested 28 two- and 56 three-drug combinations against Ebola replication. IFN-α and IFN-ß inhibited viral replication 24 hours post-infection (IC50 0.038μM and 0.016μM, respectively. 3TC, AZT and TFV inhibited Ebola replication when used alone (50-62% or in combination (87%. They exhibited lower IC50 (0.98-6.2μM compared with FPV (36.8μM, when administered 24 hours post-infection. Unexpectedly, CDF had a narrow therapeutic window (6.25-25μM. When dosed >50μM, CDF treatment enhanced viral infection. IFN-ß exhibited strong synergy with 3TC (97.3% inhibition or in triple combination with 3TC and AZT (95.8% inhibition. This study demonstrates that IFNs and viral polymerase inhibitors may have utility in EVD. We identified several 2 and 3 drug combinations with strong anti-Ebola activity, confirmed in studies using fully infectious ZEBOV, providing a rationale for testing combination therapies in animal models of lethal Ebola challenge. These studies open up new possibilities for novel therapeutic options, in particular combination therapies, which could prevent and treat Ebola infection and potentially reduce drug

  17. A novel psittacine adenovirus identified during an outbreak of avian chlamydiosis and human psittacosis: zoonosis associated with virus-bacterium coinfection in birds.

    Directory of Open Access Journals (Sweden)

    Kelvin K W To

    2014-12-01

    Full Text Available Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1 was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs with sequence similarity to known adenoviral genes, and six additional ORFs at the 3' end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3-54.0% for the DNA polymerase, 64.6-70.7% for the penton protein, and 66.1-74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention

  18. GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers.

    Directory of Open Access Journals (Sweden)

    Shengping Li

    Full Text Available Genome-wide association studies (GWAS have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV-related hepatocellular carcinoma (HCC. To further identify novel susceptibility loci associated with HBV-related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV-positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV-positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1 on 6p21.32 (OR = 1.30, P = 1.13×10⁻¹⁹ and rs455804 (GRIK1 on 21q21.3 (OR = 0.84, P = 1.86×10⁻⁸, which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10⁻⁴; rs455804: OR = 0.84, P = 6.92×10⁻³. We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV-related HCC, suggesting the involvement of glutamate signaling in the development of HBV-related HCC.

  19. Differential Expression of Wnt Pathway Genes in Sporadic Hepatocellular Carcinomas Infected With Hepatitis B Virus Identified With OligoGE Arrays.

    Science.gov (United States)

    Lin, Xiaoyan; Wang, Qiangxiu; Cao, Zhixin; Geng, Ming; Cao, Yongcheng; Liu, Xiaohong

    2013-01-01

    Epidemiological evidence has clearly indicated that chronic infection with the hepatitis B virus (HBV) is the major risk factor for developing hepatocellular carcinoma (HCC). Nonetheless, the mechanisms by which HBV contributes to the pathogenesis of HCC have not been fully elucidated. Our aim was to characterize differential gene expression profiles related to the Wnt signaling pathway between primary tumor and adjacent normal tissues in HCC patients with concomitant HBVinfection . An oligoGEArray® (an oligonucleotide-based gene expression array platform) containing 126 Wnt signaling pathway-related genes was used to compare gene expressions between primary HCC and adjacent non-tumorous liver tissues from 10 patients with HCC. Selected differential genes were identified with real-time RT-PCR and immunohistochemistry (IHC). In particular, the protein of the differential gene DVL3 (disheveled, dsh homolog 3 [Drosophila]) was chosen to investigate whether it is up regulated in primary tumor correlated with the clinic pathological characteristics of HCC patients. For this purpose we examined 56 HCC tissue samples via IHC for the presence of DVL3 protein. Sixteen genes were identified with significant differential expression between HCC and adjacent non-tumorous liver tissue. These genes have been previously associated with the Frizzled signaling pathway, cell cycle, transcription, or protein degradation. All (100%) of the tumor samples results from 56 HCC patients tested were positive for DVL3 via IHC. Based on the intensity of DVL3 immunoreactivity, 25 (44.6%) and 31 (55.4%) of the patients were classified aslow and high-DVL3, respectively, which correlated with tumor stage (P = 0.029). This study clarified a number of Wnt pathway-related genes which are dysregulated in HBV-associated HCC. These genes may be contributedto the frequent activation of the Wnt signaling pathway. Our results promote the role of the Wnt signaling pathway in HBV-associated HCC.

  20. AUTOMATIC INTERPRETATION OF HIGH RESOLUTION SAR IMAGES: FIRST RESULTS OF SAR IMAGE SIMULATION FOR SINGLE BUILDINGS

    Directory of Open Access Journals (Sweden)

    J. Tao

    2012-09-01

    Full Text Available Due to the all-weather data acquisition capabilities, high resolution space borne Synthetic Aperture Radar (SAR plays an important role in remote sensing applications like change detection. However, because of the complex geometric mapping of buildings in urban areas, SAR images are often hard to interpret. SAR simulation techniques ease the visual interpretation of SAR images, while fully automatic interpretation is still a challenge. This paper presents a method for supporting the interpretation of high resolution SAR images with simulated radar images using a LiDAR digital surface model (DSM. Line features are extracted from the simulated and real SAR images and used for matching. A single building model is generated from the DSM and used for building recognition in the SAR image. An application for the concept is presented for the city centre of Munich where the comparison of the simulation to the TerraSAR-X data shows a good similarity. Based on the result of simulation and matching, special features (e.g. like double bounce lines, shadow areas etc. can be automatically indicated in SAR image.

  1. Evaluation of InSAR and TomoSAR for Monitoring Deformations Caused by Mining in a Mountainous Area with High Resolution Satellite-Based SAR

    Directory of Open Access Journals (Sweden)

    Donglie Liu

    2014-02-01

    Full Text Available Interferometric Synthetic Aperture Radar (InSAR and Differential Interferometric Synthetic Aperture Radar (DInSAR have shown numerous applications for subsidence monitoring. In the past 10 years, the Persistent Scatterer InSAR (PSI and Small BAseline Subset (SBAS approaches were developed to overcome the problem of decorrelation and atmospheric effects, which are common in interferograms. However, DInSAR or PSI applications in rural areas, especially in mountainous regions, can be extremely challenging. In this study we have employed a combined technique, i.e., SBAS-DInSAR, to a mountainous area that is severely affected by mining activities. In addition, L-band (ALOS and C-band (ENVISAT data sets, 21 TerraSAR-X images provided by German Aerospace Center (DLR with a high resolution have been used. In order to evaluate the ability of TerraSAR-X for mining monitoring, we present a case study of TerraSAR-X SAR images for Subsidence Hazard Boundary (SHB extraction. The resulting data analysis gives an initial evaluation of InSAR applications within a mountainous region where fast movements and big phase gradients are common. Moreover, the experiment of four-dimension (4-D Tomography SAR (TomoSAR for structure monitoring inside the mining area indicates a potential near all-wave monitoring, which is an extension of conventional InSAR.

  2. SARS CoV Main Proteinase: The Monomer-Dimer Equilibrium Dissociation Constant

    Energy Technology Data Exchange (ETDEWEB)

    Graziano,V.; McGrath, W.; Yang, L.; Mangel, W.

    2006-01-01

    The SARS coronavirus main proteinase (SARS CoV main proteinase) is required for the replication of the severe acute respiratory syndrome coronavirus (SARS CoV), the virus that causes SARS. One function of the enzyme is to process viral polyproteins. The active form of the SARS CoV main proteinase is a homodimer. In the literature, estimates of the monomer-dimer equilibrium dissociation constant, K{sub D}, have varied more than 650000-fold, from <1 nM to more than 200 {mu}M. Because of these discrepancies and because compounds that interfere with activation of the enzyme by dimerization may be potential antiviral agents, we investigated the monomer-dimer equilibrium by three different techniques: small-angle X-ray scattering, chemical cross-linking, and enzyme kinetics. Analysis of small-angle X-ray scattering data from a series of measurements at different SARS CoV main proteinase concentrations yielded K{sub D} values of 5.8 {+-} 0.8 {mu}M (obtained from the entire scattering curve), 6.5 {+-} 2.2 {mu}M (obtained from the radii of gyration), and 6.8 {+-} 1.5 {mu}M (obtained from the forward scattering). The K{sub D} from chemical cross-linking was 12.7 {+-} 1.1 {mu}M, and from enzyme kinetics, it was 5.2 {+-} 0.4 {mu}M. While each of these three techniques can present different, potential limitations, they all yielded similar K{sub D} values.

  3. Safety analysis and review system (SARS) assessment report

    Energy Technology Data Exchange (ETDEWEB)

    Browne, E.T.

    1981-03-01

    Under DOE Order 5481.1, Safety Analysis and Review System for DOE Operations, safety analyses are required for DOE projects in order to ensure that: (1) potential hazards are systematically identified; (2) potential impacts are analyzed; (3) reasonable measures have been taken to eliminate, control, or mitigate the hazards; and (4) there is documented management authorization of the DOE operation based on an objective assessment of the adequacy of the safety analysis. This report is intended to provide the DOE Office of Plans and Technology Assessment (OPTA) with an independent evaluation of the adequacy of the ongoing safety analysis effort. As part of this effort, a number of site visits and interviews were conducted, and FE SARS documents were reviewed. The latter included SARS Implementation Plans for a number of FE field offices, as well as safety analysis reports completed for certain FE operations. This report summarizes SARS related efforts at the DOE field offices visited and evaluates the extent to which they fulfill the requirements of DOE 5481.1.

  4. InSAR observations of the 2009 Racha earthquake, Georgia

    Science.gov (United States)

    Nikolaeva, Elena; Walter, Thomas R.

    2016-09-01

    Central Georgia is an area strongly affected by earthquake and landslide hazards. On 29 April 1991 a major earthquake (Mw  =  7.0) struck the Racha region in Georgia, followed by aftershocks and significant afterslip. The same region was hit by another major event (Mw  =  6.0) on 7 September 2009. The aim of the study reported here was to utilize interferometric synthetic aperture radar (InSAR) data to improve knowledge about the spatial pattern of deformation due to the 2009 earthquake. There were no actual earthquake observations by InSAR in Georgia. We considered all available SAR data images from different space agencies. However, due to the long wavelength and the frequent acquisitions, only the multi-temporal ALOS L-band SAR data allowed us to produce interferograms spanning the 2009 earthquake. We detected a local uplift around 10 cm (along the line-of-sight propagation) in the interferogram near the earthquake's epicenter, whereas evidence of surface ruptures could not be found in the field along the active thrust fault. We simulated a deformation signal which could be created by the 2009 Racha earthquake on the basis of local seismic records and by using an elastic dislocation model. We compared our modeled fault surface of the September 2009 with the April 1991 Racha earthquake fault surfaces and identify the same fault or a sub-parallel fault of the same system as the origin. The patch that was active in 2009 is just adjacent to the 1991 patch, indicating a possible mainly westward propagation direction, with important implications for future earthquake hazards.

  5. Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates.

    Science.gov (United States)

    Wang, Qidi; Zhang, Lianfeng; Kuwahara, Kazuhiko; Li, Li; Liu, Zijie; Li, Taisheng; Zhu, Hua; Liu, Jiangning; Xu, Yanfeng; Xie, Jing; Morioka, Hiroshi; Sakaguchi, Nobuo; Qin, Chuan; Liu, Gang

    2016-05-13

    Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV) and has the potential to threaten global public health and socioeconomic stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine. Using antibodies from SARS patients, we identified and characterized SARS-CoV B-cell peptide epitopes with disparate functions. In rhesus macaques, the spike glycoprotein peptides S471-503, S604-625, and S1164-1191 elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S597-603 induced antibodies that enhanced infection both in vitro and in non-human primates by using an epitope sequence-dependent (ESD) mechanism. This peptide exhibited a high level of serological reactivity (64%), which resulted from the additive responses of two tandem epitopes (S597-603 and S604-625) and a long-term human B-cell memory response with antisera from convalescent SARS patients. Thus, peptide-based vaccines against SARS-CoV could be engineered to avoid ADE via elimination of the S597-603 epitope. We provide herein an alternative strategy to prepare a safe and effective vaccine for ADE of viral infection by identifying and eliminating epitope sequence-dependent enhancement of viral infection.

  6. MiTAP for SARS Detection

    National Research Council Canada - National Science Library

    Damianos, Laurie E; Bayer, Samuel; Chisholm, Michael A; Henderson, John; Hirschman, Lynette; Morgan, William; Ubaldino, Marc; Zarrella, Guido; Wilson, V, James M; Polyak, Marat G

    2006-01-01

    The MiTAP prototype for SARS detection uses human language technology for detecting, monitoring, and analyzing potential indicators of infectious disease outbreaks and reasoning for issuing warnings and alerts...

  7. Attribute Learning for SAR Image Classification

    Directory of Open Access Journals (Sweden)

    Chu He

    2017-04-01

    Full Text Available This paper presents a classification approach based on attribute learning for high spatial resolution Synthetic Aperture Radar (SAR images. To explore the representative and discriminative attributes of SAR images, first, an iterative unsupervised algorithm is designed to cluster in the low-level feature space, where the maximum edge response and the ratio of mean-to-variance are included; a cross-validation step is applied to prevent overfitting. Second, the most discriminative clustering centers are sorted out to construct an attribute dictionary. By resorting to the attribute dictionary, a representation vector describing certain categories in the SAR image can be generated, which in turn is used to perform the classifying task. The experiments conducted on TerraSAR-X images indicate that those learned attributes have strong visual semantics, which are characterized by bright and dark spots, stripes, or their combinations. The classification method based on these learned attributes achieves better results.

  8. A New Approach for SAR Image Denoising

    National Research Council Canada - National Science Library

    Murali Mohan Babu Y; Subramanyam M V; Giri Prasad M N

    2015-01-01

      In synthetic aperture radar (SAR) imaging, the transmitted pulses from space born antenna interacts with ground objects and returned energy or back scattered energy will be collected to get backscattered image...

  9. Satellite sar detection of hurricane helene (2006)

    DEFF Research Database (Denmark)

    Ju, Lian; Cheng, Yongcun; Xu, Qing

    2013-01-01

    In this paper, the wind structure of hurricane Helene (2006) over the Atlantic Ocean is investigated from a C-band RADARSAT-1 synthetic aperture radar (SAR) image acquired on 20 September 2006. First, the characteristics, e.g., the center, scale and area of the hurricane eye (HE) are determined....... There is a good agreement between the SAR-estimated HE center location and the best track data from the National Hurricane Center. The wind speeds at 10 m above the ocean surface are also retrieved from the SAR data using the geophysical model function (GMF), CMOD5, and compared with in situ wind speed...... observations from the stepped frequency microwave radiometer (SFMR) on NOAA P3 aircraft. All the results show the capability of hurricane monitoring by satellite SAR. Copyright © 2013 by the International Society of Offshore and Polar Engineers (ISOPE)....

  10. Advanced Antenna for Digital Beamforming SAR Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Develop a wideband (500 MHz) L-band phased-array antenna for airborne Synthetic Aperture Radar (SAR) applications based on a novel approach that will make possible...

  11. Metagenomic study of the viruses of African straw-coloured fruit bats: detection of a chiropteran poxvirus and isolation of a novel adenovirus.

    Science.gov (United States)

    Baker, Kate S; Leggett, Richard M; Bexfield, Nicholas H; Alston, Mark; Daly, Gordon; Todd, Shawn; Tachedjian, Mary; Holmes, Clare E G; Crameri, Sandra; Wang, Lin-Fa; Heeney, Jonathan L; Suu-Ire, Richard; Kellam, Paul; Cunningham, Andrew A; Wood, James L N; Caccamo, Mario; Murcia, Pablo R

    2013-07-05

    Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. SARS among Critical Care Nurses, Toronto

    Science.gov (United States)

    McGeer, Allison; Henry, Bonnie; Ofner, Marianna; Rose, David; Hlywka, Tammy; Levie, Joanne; McQueen, Jane; Smith, Stephanie; Moss, Lorraine; Smith, Andrew; Green, Karen; Walter, Stephen D.

    2004-01-01

    To determine factors that predispose or protect healthcare workers from severe acute respiratory syndrome (SARS), we conducted a retrospective cohort study among 43 nurses who worked in two Toronto critical care units with SARS patients. Eight of 32 nurses who entered a SARS patient’s room were infected. The probability of SARS infection was 6% per shift worked. Assisting during intubation, suctioning before intubation, and manipulating the oxygen mask were high-risk activities. Consistently wearing a mask (either surgical or particulate respirator type N95) while caring for a SARS patient was protective for the nurses, and consistent use of the N95 mask was more protective than not wearing a mask. Risk was reduced by consistent use of a surgical mask, but not significantly. Risk was lower with consistent use of a N95 mask than with consistent use of a surgical mask. We conclude that activities related to intubation increase SARS risk and use of a mask (particularly a N95 mask) is protective. PMID:15030692

  13. Ionospheric Specifications for SAR Interferometry (ISSI)

    Science.gov (United States)

    Pi, Xiaoqing; Chapman, Bruce D; Freeman, Anthony; Szeliga, Walter; Buckley, Sean M.; Rosen, Paul A.; Lavalle, Marco

    2013-01-01

    The ISSI software package is designed to image the ionosphere from space by calibrating and processing polarimetric synthetic aperture radar (PolSAR) data collected from low Earth orbit satellites. Signals transmitted and received by a PolSAR are subject to the Faraday rotation effect as they traverse the magnetized ionosphere. The ISSI algorithms combine the horizontally and vertically polarized (with respect to the radar system) SAR signals to estimate Faraday rotation and ionospheric total electron content (TEC) with spatial resolutions of sub-kilometers to kilometers, and to derive radar system calibration parameters. The ISSI software package has been designed and developed to integrate the algorithms, process PolSAR data, and image as well as visualize the ionospheric measurements. A number of tests have been conducted using ISSI with PolSAR data collected from various latitude regions using the phase array-type L-band synthetic aperture radar (PALSAR) onboard Japan Aerospace Exploration Agency's Advanced Land Observing Satellite mission, and also with Global Positioning System data. These tests have demonstrated and validated SAR-derived ionospheric images and data correction algorithms.

  14. SAR Tomography Based on Block Compressive Sensing

    Directory of Open Access Journals (Sweden)

    Wang Aichun

    2016-02-01

    Full Text Available While the use of SAR Tomography (TomoSAR based on Compressive Sensing (CS makes it possible to reconstruct the height profile of an observed scene, the performance of the reconstruction decreases for a structural observed scene. To deal with this issue, we propose using TomoSAR based on Block Compressive Sensing (BCS, which changes the reconstruction of the structural observed scene into a BCS problem under the principles of CS. Further, the block size is established by utilizing the relationship between the characteristics of the structural observed scene and the SAR parameters, such that the BCS problem is efficiently solved with a block sparse l1/l2 norm optimization signal model. Compared with existing CSTomoSAR methods, the proposed BCS-TomoSAR method makes better use of the sparsity and structure information of a structural observed scene, and has higher precision and better reconstruction performance. We used simulations and Radarsat-2 data to verify the effectiveness of this proposed method.

  15. Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach.

    Directory of Open Access Journals (Sweden)

    Dong Ding

    Full Text Available Integration of the viral DNA into host chromosomes was found in most of the hepatitis B virus (HBV-related hepatocellular carcinomas (HCCs. Here we devised a massive anchored parallel sequencing (MAPS method using next-generation sequencing to isolate and sequence HBV integrants. Applying MAPS to 40 pairs of HBV-related HCC tissues (cancer and adjacent tissues, we identified 296 HBV integration events corresponding to 286 unique integration sites (UISs with precise HBV-Human DNA junctions. HBV integration favored chromosome 17 and preferentially integrated into human transcript units. HBV targeted genes were enriched in GO terms: cAMP metabolic processes, T cell differentiation and activation, TGF beta receptor pathway, ncRNA catabolic process, and dsRNA fragmentation and cellular response to dsRNA. The HBV targeted genes include 7 genes (PTPRJ, CNTN6, IL12B, MYOM1, FNDC3B, LRFN2, FN1 containing IPR003961 (Fibronectin, type III domain, 7 genes (NRG3, MASP2, NELL1, LRP1B, ADAM21, NRXN1, FN1 containing IPR013032 (EGF-like region, conserved site, and three genes (PDE7A, PDE4B, PDE11A containing IPR002073 (3', 5'-cyclic-nucleotide phosphodiesterase. Enriched pathways include hsa04512 (ECM-receptor interaction, hsa04510 (Focal adhesion, and hsa04012 (ErbB signaling pathway. Fewer integration events were found in cancers compared to cancer-adjacent tissues, suggesting a clonal expansion model in HCC development. Finally, we identified 8 genes that were recurrent target genes by HBV integration including fibronectin 1 (FN1 and telomerase reverse transcriptase (TERT1, two known recurrent target genes, and additional novel target genes such as SMAD family member 5 (SMAD5, phosphatase and actin regulator 4 (PHACTR4, and RNA binding protein fox-1 homolog (C. elegans 1 (RBFOX1. Integrating analysis with recently published whole-genome sequencing analysis, we identified 14 additional recurrent HBV target genes, greatly expanding the HBV recurrent target list

  16. From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.

    Science.gov (United States)

    Hilgenfeld, Rolf; Peiris, Malik

    2013-10-01

    This article introduces a series of invited papers in Antiviral Research marking the 10th anniversary of the outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus that emerged in southern China in late 2002. Until that time, coronaviruses had not been recognized as agents causing severe disease in humans, hence, the emergence of the SARS-CoV came as a complete surprise. Research during the past ten years has revealed the existence of a diverse pool of coronaviruses circulating among various bat species and other animals, suggesting that further introductions of highly pathogenic coronaviruses into the human population are not merely probable, but inevitable. The recent emergence of another coronavirus causing severe disease, Middle East respiratory syndrome (MERS), in humans, has made it clear that coronaviruses pose a major threat to human health, and that more research is urgently needed to elucidate their replication mechanisms, identify potential drug targets, and develop effective countermeasures. In this series, experts in many different aspects of coronavirus replication and disease will provide authoritative, up-to-date reviews of the following topics: - clinical management and infection control of SARS; - reservoir hosts of coronaviruses; - receptor recognition and cross-species transmission of SARS-CoV; - SARS-CoV evasion of innate immune responses; - structures and functions of individual coronaviral proteins; - anti-coronavirus drug discovery and development; and - the public health legacy of the SARS outbreak. Each article will be identified in the last line of its abstract as belonging to the series "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses." Copyright © 2013 Elsevier B.V. All rights reserved.

  17. NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion.

    Science.gov (United States)

    Mahajan, Mukesh; Chatterjee, Deepak; Bhuvaneswari, Kannaian; Pillay, Shubhadra; Bhattacharjya, Surajit

    2018-02-01

    The lethal Coronaviruses (CoVs), Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV) and most recently Middle East Respiratory Syndrome Coronavirus, (MERS-CoV) are serious human health hazard. A successful viral infection requires fusion between virus and host cells carried out by the surface spike glycoprotein or S protein of CoV. Current models propose that the S2 subunit of S protein assembled into a hexameric helical bundle exposing hydrophobic fusogenic peptides or fusion peptides (FPs) for membrane insertion. The N-terminus of S2 subunit of SARS-CoV reported to be active in cell fusion whereby FPs have been identified. Atomic-resolution structure of FPs derived either in model membranes or in membrane mimic environment would glean insights toward viral cell fusion mechanism. Here, we have solved 3D structure, dynamics and micelle localization of a 64-residue long fusion peptide or LFP in DPC detergent micelles by NMR methods. Micelle bound structure of LFP is elucidated by the presence of discretely folded helical and intervening loops. The C-terminus region, residues F42-Y62, displays a long hydrophobic helix, whereas the N-terminus is defined by a short amphipathic helix, residues R4-Q12. The intervening residues of LFP assume stretches of loops and helical turns. The N-terminal helix is sustained by close aromatic and aliphatic sidechain packing interactions at the non-polar face. 15N{1H}NOE studies indicated dynamical motion, at ps-ns timescale, of the helices of LFP in DPC micelles. PRE NMR showed that insertion of several regions of LFP into DPC micelle core. Together, the current study provides insights toward fusion mechanism of SARS-CoV. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. A novel nonsegmented double-stranded RNA mycovirus identified in the phytopathogenic fungus Nigrospora oryzae shows similarity to partitivirus-like viruses.

    Science.gov (United States)

    Zhou, Qian; Zhong, Jie; Hu, Yue; Da Gao, Bi

    2016-01-01

    Nigrospora oryzae is a pathogen that can infect plants of various species. Here, we report the isolation of a novel mycovirus from N. oryzae infecting rice, as well as the complete genome sequence and genomic organization of this virus, which we have named "Nigrospora oryzae nonsegmented RNA virus 1" (NoNRV1). The genome of NoNRV1 contained two non-overlapping open reading frames (ORF1 and ORF2) potentially encoding a protein with an unknown function in ORF1 and a putative RNA-dependent RNA polymerase (RdRp) in ORF2. Homology and phylogenetic analysis revealed that NoNRV1 was most similar to the Ustilaginoidea virens nonsegmented virus 1 (UvNV-1) and distantly related to members of the virus family Partitiviridae. It is proposed that NoNRV1, together with UvNV-1 and other related viruses, might represent a novel virus taxon of mycoviruses belonging to a partitivirus-like lineage.

  19. Deep sequencing reveals the complete genome and evidence for transcriptional activity of the first virus-like sequences identified in Aristotelia chilensis (Maqui Berry).

    Science.gov (United States)

    Villacreses, Javier; Rojas-Herrera, Marcelo; Sánchez, Carolina; Hewstone, Nicole; Undurraga, Soledad F; Alzate, Juan F; Manque, Patricio; Maracaja-Coutinho, Vinicius; Polanco, Victor

    2015-04-03

    Here, we report the genome sequence and evidence for transcriptional activity of a virus-like element in the native Chilean berry tree Aristotelia chilensis. We propose to name the endogenous sequence as Aristotelia chilensis Virus 1 (AcV1). High-throughput sequencing of the genome of this tree uncovered an endogenous viral element, with a size of 7122 bp, corresponding to the complete genome of AcV1. Its sequence contains three open reading frames (ORFs): ORFs 1 and 2 shares 66%-73% amino acid similarity with members of the Caulimoviridae virus family, especially the Petunia vein clearing virus (PVCV), Petuvirus genus. ORF1 encodes a movement protein (MP); ORF2 a Reverse Transcriptase (RT) and a Ribonuclease H (RNase H) domain; and ORF3 showed no amino acid sequence similarity with any other known virus proteins. Analogous to other known endogenous pararetrovirus sequences (EPRVs), AcV1 is integrated in the genome of Maqui Berry and showed low viral transcriptional activity, which was detected by deep sequencing technology (DNA and RNA-seq). Phylogenetic analysis of AcV1 and other pararetroviruses revealed a closer resemblance with Petuvirus. Overall, our data suggests that AcV1 could be a new member of Caulimoviridae family, genus Petuvirus, and the first evidence of this kind of virus in a fruit plant.

  20. InSAR Scientific Computing Environment

    Science.gov (United States)

    Rosen, Paul A.; Sacco, Gian Franco; Gurrola, Eric M.; Zabker, Howard A.

    2011-01-01

    This computing environment is the next generation of geodetic image processing technology for repeat-pass Interferometric Synthetic Aperture (InSAR) sensors, identified by the community as a needed capability to provide flexibility and extensibility in reducing measurements from radar satellites and aircraft to new geophysical products. This software allows users of interferometric radar data the flexibility to process from Level 0 to Level 4 products using a variety of algorithms and for a range of available sensors. There are many radar satellites in orbit today delivering to the science community data of unprecedented quantity and quality, making possible large-scale studies in climate research, natural hazards, and the Earth's ecosystem. The proposed DESDynI mission, now under consideration by NASA for launch later in this decade, would provide time series and multiimage measurements that permit 4D models of Earth surface processes so that, for example, climate-induced changes over time would become apparent and quantifiable. This advanced data processing technology, applied to a global data set such as from the proposed DESDynI mission, enables a new class of analyses at time and spatial scales unavailable using current approaches. This software implements an accurate, extensible, and modular processing system designed to realize the full potential of InSAR data from future missions such as the proposed DESDynI, existing radar satellite data, as well as data from the NASA UAVSAR (Uninhabited Aerial Vehicle Synthetic Aperture Radar), and other airborne platforms. The processing approach has been re-thought in order to enable multi-scene analysis by adding new algorithms and data interfaces, to permit user-reconfigurable operation and extensibility, and to capitalize on codes already developed by NASA and the science community. The framework incorporates modern programming methods based on recent research, including object-oriented scripts controlling legacy and

  1. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum.

    Directory of Open Access Journals (Sweden)

    Kèvin Knoops

    2008-09-01

    Full Text Available Positive-strand RNA viruses, a large group including human pathogens such as SARS-coronavirus (SARS-CoV, replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified host cell membranes. Membrane structures supporting viral RNA synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. Generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to be defined. Poorly characterized double-membrane vesicles (DMVs were previously implicated in SARS-CoV RNA synthesis. We have now applied electron tomography of cryofixed infected cells for the three-dimensional imaging of coronavirus-induced membrane alterations at high resolution. Our analysis defines a unique reticulovesicular network of modified endoplasmic reticulum that integrates convoluted membranes, numerous interconnected DMVs (diameter 200-300 nm, and "vesicle packets" apparently arising from DMV merger. The convoluted membranes were most abundantly immunolabeled for viral replicase subunits. However, double-stranded RNA, presumably revealing the site of viral RNA synthesis, mainly localized to the DMV interior. Since we could not discern a connection between DMV interior and cytosol, our analysis raises several questions about the mechanism of DMV formation and the actual site of SARS-CoV RNA synthesis. Our data document the extensive virus-induced reorganization of host cell membranes into a network that is used to organize viral replication and possibly hide replicating RNA from antiviral defense mechanisms. Together with biochemical studies of the viral enzyme complex, our ultrastructural description of this "replication network" will aid to further dissect the early stages of the coronavirus life cycle and its virus-host interactions.

  2. Landslide risk assessment with multi pass DInSAR analysis and error suppressing approach

    Science.gov (United States)

    yun, H.; Kim, J.; Lin, S.; Choi, Y.

    2013-12-01

    ) which was newly developed for extracting the reliable deformation values even with the presence of error terms and two pass DInSAR with the error term compensation based on the external weather information using L band ALOS PALSAR and C band ENVISAT ASAR. Since MERIS Reduced Resolution (RR) coverage over target areas includes a few cloud free scenes, the water vapor map constructions were feasible with 1.2km spatial resolutions in two pass DInSAR pairs and enable to assess the deformation measurement of StaMPS/MTI by the inter comparison. Although the correlation between deformation patterns from two pass DInSAR and StaMPS was not very clearly identified in this study, the deformation values and the landslide triggering factors showed some agreements. Thus the quantitative landslide monitoring scheme is supposedly feasible on the condition that the high accuracy atmospheric error map and the methodology effectively compensating it from DInSAR interferograms are available. The scheme in this study will be further upgraded for the application of future C, X and L band SAR by incorporating the spaceborne radiometer and/or weather forecasting model to establish electromagnetic wave delay map.

  3. Expression of contactin associated protein-like 2 in a subset of hepatic progenitor cell compartment identified by gene expression profiling in hepatitis B virus-positive cirrhosis.

    Science.gov (United States)

    Wang, Huafeng; Gao, Yabo; Jin, Xiaolong; Xiao, Jiacheng

    2010-01-01

    Hepatic progenitor cells (HPC), a cell compartment capable of differentiating into hepatocytic and biliary lineages, may give rise to the formation of intermediate hepatobiliary cells (IHBC) or ductular reactions (DR). The aim of this study was to analyse the gene expression profiles of DR in cirrhosis and further investigate novel proteins expressed by HPC and their intermediate progeny. DR in hepatitis B virus (HBV)-positive cirrhotic liver tissues adjacent to hepatocellular carcinoma and interlobular bile ducts (ILBDs) in normal liver tissues were isolated by laser capture microdissection and then subjected to microarray analysis. Differential gene expression patterns were verified by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry on serial sections. HPC and their intermediate progeny were recognized by immunostaining with hepatocytic and biliary markers [HepPar1, cytokeratin (CK)7, CK19, neural cell adhesion molecule (NCAM), epithelial cell adhesion molecule (EpCAM)]. A total of 88 genes showed upregulation in DR compared with ILBDs. Gene ontology analyses revealed that these upregulated genes were mostly associated with cell adhesion, immune response and the metabolic process. Contactin associated protein-like 2 (CNTNAP2) was first confirmed to be a novel protein expressed in a subpopulation of DR that was positive for CK7, NCAM or EpCAM. In addition, immunoreactivity for CNTNAP2 was also noted in a subset of isolated CK7-positive HPC as well as some ductular IHBC positive for CK19 and HepPar1 in DR. CNTNAP2 is specifically associated with the emergence of ductular populations and may be identified as a novel protein for defining a subset of HPC and their intermediate progeny in cirrhosis.

  4. Peroxiredoxin 2: a potential biomarker for early diagnosis of Hepatitis B Virus related liver fibrosis identified by proteomic analysis of the plasma

    Directory of Open Access Journals (Sweden)

    Wang Haijian

    2010-10-01

    Full Text Available Abstract Background Liver fibrosis is a middle stage in the course of chronic Hepatitis B virus (HBV infection, which will develop into cirrhosis and eventually hepatocellular carcinoma (HCC if not treated at the early stage. Considering the limitations and patients' reluctance to undergo liver biopsy, a reliable, noninvasive diagnostic system to predict and assess treatment and prognosis of liver fibrosis is needed. The aim of this study was to identify biomarkers for early diagnosis of HBV related liver fibrosis. Method Plasma samples from 7 healthy volunteers and 27 HBV infected patients with different stages of fibrosis were selected for 2-DIGE proteomic screening. One-way ANOVA analysis was used to assess differences in protein expression among all groups. The alteration was further confirmed by western blotting. Plasma levels of 25 serological variables in 42 healthy volunteers and 68 patients were measured to establish a decision tree for the detection of various stages fibrosis. Result The up-regulated proteins along with fibrosis progress included fibrinogen, collagen, macroglobulin, hemopexin, antitrypsin, prealbumin and thioredoxin peroxidase. The down-regulated proteins included haptoglobin, serotransferrin, CD5 antigen like protein, clusterin, apolipoprotein and leucine-rich alpha-2-glycoprotein. For the discrimination of milder stage fibrosis, the area under curve for Prx II was the highest. Four variables (PT, Pre, HA and Prx II were selected from the 25 variables to construct the decision tree. In a training group, the correct prediction percentage for normal control, milder fibrosis, significant fibrosis and early cirrhosis was 100%, 88.9%, 95.2% and 100%, respectively, with an overall correct percent of 95.9%. Conclusion This study showed that 2-D DIGE-based proteomic analysis of the plasma was helpful in screening for new plasma biomarkers for liver disease. The significant up-expression of Prx II could be used in the early

  5. Advanced InSAR imaging for dune mapping

    Science.gov (United States)

    Havivi, Shiran; August, Yitzhak; Blumberg, Dan G.; Rotman, Stanley R.

    2015-04-01

    Aeolian morphologies are formed in the presence of sufficient wind energy and available particles. These processes occur naturally or are further enhanced or reduced by human intervention. The dimensions of change are dependent primarily on the wind energy and surface properties. Since the 1970's, remote sensing imagery both optical and radar, are used for documentation and interpretation of the geomorphologic changes of sand dunes. Remote sensing studies of Aeolian morphologies is mostly useful to document major changes, yet, subtle changes, occurring in a period of days or months in scales of centimeters, are very difficult to detect in imagery. Interferometric Synthetic Aperture Radar (InSAR) is an imaging technique for measuring Earth's surface topography and deformation. InSAR images are produced by measuring the radar phase difference between two separated antennas that view the same surface area. Classical InSAR is based on high coherence between two images or more. The output (interferogram) can show subtle changes with an accuracy of several millimeters to centimeters. Very little work has been done on measuring or identifying the changes in dunes using InSAR. The reason is that dunes tend to be less coherent than firm, stable, surfaces. This research aims to demonstrate how interferometric decorrelation, or, coherence change detection, can be used for identifying dune instability. We hypothesize and demonstrate that the loss of radar coherence over time on dunes can be used as an indication of the dune's instability. When SAR images are acquired at sufficiently close intervals one can measure the time it takes to lose coherence and associate this time with geomorphic stability. To achieve our goals, the Nitzanim coastal dunes along the Mediterranean, 40 km south of Tel-Aviv, Israel, were chosen as a case study. The dunes in this area are of varying levels of stability and vegetation cover and have been monitored meteorologically, geomorphologically and

  6. UAVSAR: InSAR and PolSAR Test Bed for the Proposed NI-SAR Mission

    Science.gov (United States)

    Jones, C. E.; Hensley, S.; Lou, Y.

    2014-12-01

    UAVSAR, which first became operational in 2009, has served as an operational testbed for the NI-SAR L-band radar concept and a unique instrument in its own right. UAVSAR supports a broad array of basic and applied geoscience, covering on smaller scale all the disciplines NI-SAR would be able to address on a global scale. Although designed specifically to provide high accuracy repeated flight tracks and precise imaging geometry for InSAR-based solid earth studies, its fully polarimetric operation, low noise, and consistent calibration accuracy has made it a premier instrument for PolSAR-based studies also. Since 2009 it has successfully imaged more than 16 million km2 and >4300 quad-polarimetric data products are now publicly available online. Upgrades made in the last year to automate the repeat track processing serve as a model for generating large volumes of InSAR products: Since January 2014 more than 700 interferometric products have been released, exceeding the output of all previous years combined. Standardly available products now include browse images of all InSAR acquisitions and coregistered single-look complex image stacks suitable for standard time series analysis. Here we present an overview of the wide range of studies utilizing UAVSAR data including those based on polarimetry and pair-wise and times series interferometry, highlighting both the unique capabilities of UAVSAR and the ways in which NI-SAR would be able to dramatically extend the capabilities. This research was conducted at the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.

  7. Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2.

    Science.gov (United States)

    Reinke, Lennart Michel; Spiegel, Martin; Plegge, Teresa; Hartleib, Anika; Nehlmeier, Inga; Gierer, Stefanie; Hoffmann, Markus; Hofmann-Winkler, Heike; Winkler, Michael; Pöhlmann, Stefan

    2017-01-01

    The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.

  8. Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2

    Science.gov (United States)

    Reinke, Lennart Michel; Hartleib, Anika; Nehlmeier, Inga; Gierer, Stefanie; Hoffmann, Markus; Hofmann-Winkler, Heike; Winkler, Michael

    2017-01-01

    The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated. PMID:28636671

  9. Online Health Education on SARS to University Students during the SARS Outbreak

    Science.gov (United States)

    Wong, Mee Lian; Koh, David; Iyer, Prasad; Seow, Adeline; Goh, Lee Gan; Chia, Sin Eng; Lim, Meng Kin; Ng, Daniel; Ong, Choon Nam; Phua, Kai Hong; Tambyah, Paul; Chow, Vincent T K; Chew, Suok Kai; Chandran, Ravi; Lee, Hin Peng

    2005-01-01

    Little is known about how online learning may be used to disseminate health information rapidly and widely to large university populations if there is an infectious disease outbreak. During the SARS outbreak in Singapore in 2003, a six-lesson elearning module on SARS was developed for a large university population of 32,000 students. The module…

  10. SAR-PC: Edge Detection in SAR Images via an Advanced Phase Congruency Model

    Directory of Open Access Journals (Sweden)

    Yuming Xiang

    2017-02-01

    Full Text Available Edge detection in Synthetic Aperture Radar (SAR images has been a challenging task due to the speckle noise. Ratio-based edge detectors are robust operators for SAR images that provide constant false alarm rates, but they are only optimal for step edges. Edge detectors developed by the phase congruency model provide the identification of different types of edge features, but they suffer from speckle noise. By combining the advantages of the two edge detectors, we propose a SAR phase congruency detector (SAR-PC. Firstly, an improved local energy model for SAR images is obtained by replacing the convolution of raw image and the quadrature filters by the ratio responses. Secondly, a new noise level is estimated for the multiplicative noise. Substituting the SAR local energy and the new noise level into the phase congruency model, SAR-PC is derived. Edge response corresponds to the max moment of SAR-PC. We compare the proposed detector with the ratio-based edge detectors and the phase congruency edge detectors. Receiver Operating Characteristic (ROC curves and visual effects are used to evaluate the performance. Experimental results of simulated images and real-world images show that the proposed edge detector is robust to speckle noise and it provides a consecutive edge response.

  11. A Simple Screening Approach To Prioritize Genes for Functional Analysis Identifies a Role for Interferon Regulatory Factor 7 in the Control of Respiratory Syncytial Virus Disease.

    Science.gov (United States)

    McDonald, Jacqueline U; Kaforou, Myrsini; Clare, Simon; Hale, Christine; Ivanova, Maria; Huntley, Derek; Dorner, Marcus; Wright, Victoria J; Levin, Michael; Martinon-Torres, Federico; Herberg, Jethro A; Tregoning, John S

    2016-01-01

    Greater understanding of the functions of host gene products in response to infection is required. While many of these genes enable pathogen clearance, some enhance pathogen growth or contribute to disease symptoms. Many studies have profiled transcriptomic and proteomic responses to infection, generating large data sets, but selecting targets for further study is challenging. Here we propose a novel data-mining approach combining multiple heterogeneous data sets to prioritize genes for further study by using respiratory syncytial virus (RSV) infection as a model pathogen with a significant health care impact. The assumption was that the more frequently a gene is detected across multiple studies, the more important its role is. A literature search was performed to find data sets of genes and proteins that change after RSV infection. The data sets were standardized, collated into a single database, and then panned to determine which genes occurred in multiple data sets, generating a candidate gene list. This candidate gene list was validated by using both a clinical cohort and in vitro screening. We identified several genes that were frequently expressed following RSV infection with no assigned function in RSV control, including IFI27, IFIT3, IFI44L, GBP1, OAS3, IFI44, and IRF7. Drilling down into the function of these genes, we demonstrate a role in disease for the gene for interferon regulatory factor 7, which was highly ranked on the list, but not for IRF1, which was not. Thus, we have developed and validated an approach for collating published data sets into a manageable list of candidates, identifying novel targets for future analysis. IMPORTANCE Making the most of "big data" is one of the core challenges of current biology. There is a large array of heterogeneous data sets of host gene responses to infection, but these data sets do not inform us about gene function and require specialized skill sets and training for their utilization. Here we describe an

  12. Re-evaluation of hepatitis B virus clinical phases by systems biology identifies unappreciated roles for the innate immune response and B cells.

    Science.gov (United States)

    Vanwolleghem, Thomas; Hou, Jun; van Oord, Gertine; Andeweg, Arno C; Osterhaus, A D M E; Pas, Suzan D; Janssen, Harry L A; Boonstra, Andre

    2015-07-01

    To identify immunological mechanisms that govern distinct clinical phases of a chronic hepatitis B virus (HBV) infection-immune tolerant (IT), immune active (IA), inactive carrier (IC), and hepatitis B e antigen (HBeAg)-negative (ENEG) hepatitis phases-we performed a systems biology study. Serum samples from untreated chronic HBV patients (n = 71) were used for multiplex cytokine measurements, quantitative hepatitis B surface antigen (HBsAg), HBeAg levels, HBV genotype, and mutant analysis. Leukocytes were phenotyped using multicolor flow cytometry, and whole-blood transcriptome profiles were generated. The latter were compared with liver biopsy transcriptomes from IA (n = 16) and IT (n = 3) patients. HBV viral load as well as HBeAg and HBsAg levels (P < 0.001), but not leukocyte composition, differed significantly between distinct phases. Serum macrophage chemotactic protein 1, interleukin-12p40, interferon (IFN)-gamma-inducible protein 10, and macrophage inflammatory protein 1 beta levels were different between two or more clinical phases (P < 0.05). Comparison of blood transcriptomes identified 64 differentially expressed genes. The gene signature distinguishing IA from IT and IC patients was predominantly composed of highly up-regulated immunoglobulin-encoding genes. Modular repertoire analysis using gene sets clustered according to similar expression patterns corroborated the abundant expression of B-cell function-related genes in IA patients and pointed toward increased (ISG) transcript levels in IT patients, compared to subsequent phases. Natural killer cell activities were clustered in clinical phases with biochemical liver damage (IA and ENEG phases), whereas T-cell activities were higher in all phases, compared to IT patients. B-cell-related transcripts proved to be higher in biopsies from IA versus IT patients. HBV clinical phases are characterized by distinct blood gene signatures. Innate IFN and B-cell responses are highly active

  13. Satellite SAR interferometry for monitoring dam deformation in Portugal

    OpenAIRE

    Joaquim, Sousa; Lazecky, Milan; Hlavacova, Ivana; Bakon, Matus; Patrício, Glória

    2016-01-01

    The paper offers three examples of satellite SAR interferometry (InSAR) application for monitoring dam deformations: Paradela, Raiva and Alto Ceira, all of them in Portugal. Dam deformations were estimated using several sets of ERS and Envisat C-band SAR data by PS-InSAR method that offers accuracy of a millimeter per year at monitoring man-made tructures. The results show potential of InSAR but also summarize limits of C-band InSAR in these particular cases and can be handful to recogn...

  14. Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection.

    Science.gov (United States)

    Channappanavar, Rudragouda; Fett, Craig; Zhao, Jincun; Meyerholz, David K; Perlman, Stanley

    2014-10-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection. Virus-specific CD8 T cells are required for pathogen clearance following primary SARS-CoV infection. However, the role of SARS-CoV-specific memory CD

  15. European surveillance network for influenza in pigs: surveillance programs, diagnostic tools and Swine influenza virus subtypes identified in 14 European countries from 2010 to 2013.

    Directory of Open Access Journals (Sweden)

    Gaëlle Simon

    Full Text Available Swine influenza causes concern for global veterinary and public health officials. In continuing two previous networks that initiated the surveillance of swine influenza viruses (SIVs circulating in European pigs between 2001 and 2008, a third European Surveillance Network for Influenza in Pigs (ESNIP3, 2010-2013 aimed to expand widely the knowledge of the epidemiology of European SIVs. ESNIP3 stimulated programs of harmonized SIV surveillance in European countries and supported the coordination of appropriate diagnostic tools and subtyping methods. Thus, an extensive virological monitoring, mainly conducted through passive surveillance programs, resulted in the examination of more than 9 000 herds in 17 countries. Influenza A viruses were detected in 31% of herds examined from which 1887 viruses were preliminary characterized. The dominating subtypes were the three European enzootic SIVs: avian-like swine H1N1 (53.6%, human-like reassortant swine H1N2 (13% and human-like reassortant swine H3N2 (9.1%, as well as pandemic A/H1N1 2009 (H1N1pdm virus (10.3%. Viruses from these four lineages co-circulated in several countries but with very different relative levels of incidence. For instance, the H3N2 subtype was not detected at all in some geographic areas whereas it was still prevalent in other parts of Europe. Interestingly, H3N2-free areas were those that exhibited highest frequencies of circulating H1N2 viruses. H1N1pdm viruses were isolated at an increasing incidence in some countries from 2010 to 2013, indicating that this subtype has become established in the European pig population. Finally, 13.9% of the viruses represented reassortants between these four lineages, especially between previous enzootic SIVs and H1N1pdm. These novel viruses were detected at the same time in several countries, with increasing prevalence. Some of them might become established in pig herds, causing implications for zoonotic infections.

  16. European Surveillance Network for Influenza in Pigs: Surveillance Programs, Diagnostic Tools and Swine Influenza Virus Subtypes Identified in 14 European Countries from 2010 to 2013

    Science.gov (United States)

    Simon, Gaëlle; Larsen, Lars E.; Dürrwald, Ralf; Foni, Emanuela; Harder, Timm; Van Reeth, Kristien; Markowska-Daniel, Iwona; Reid, Scott M.; Dan, Adam; Maldonado, Jaime; Huovilainen, Anita; Billinis, Charalambos; Davidson, Irit; Agüero, Montserrat; Vila, Thaïs; Hervé, Séverine; Breum, Solvej Østergaard; Chiapponi, Chiara; Urbaniak, Kinga; Kyriakis, Constantinos S.; Brown, Ian H.; Loeffen, Willie

    2014-01-01

    Swine influenza causes concern for global veterinary and public health officials. In continuing two previous networks that initiated the surveillance of swine influenza viruses (SIVs) circulating in European pigs between 2001 and 2008, a third European Surveillance Network for Influenza in Pigs (ESNIP3, 2010–2013) aimed to expand widely the knowledge of the epidemiology of European SIVs. ESNIP3 stimulated programs of harmonized SIV surveillance in European countries and supported the coordination of appropriate diagnostic tools and subtyping methods. Thus, an extensive virological monitoring, mainly conducted through passive surveillance programs, resulted in the examination of more than 9 000 herds in 17 countries. Influenza A viruses were detected in 31% of herds examined from which 1887 viruses were preliminary characterized. The dominating subtypes were the three European enzootic SIVs: avian-like swine H1N1 (53.6%), human-like reassortant swine H1N2 (13%) and human-like reassortant swine H3N2 (9.1%), as well as pandemic A/H1N1 2009 (H1N1pdm) virus (10.3%). Viruses from these four lineages co-circulated in several countries but with very different relative levels of incidence. For instance, the H3N2 subtype was not detected at all in some geographic areas whereas it was still prevalent in other parts of Europe. Interestingly, H3N2-free areas were those that exhibited highest frequencies of circulating H1N2 viruses. H1N1pdm viruses were isolated at an increasing incidence in some countries from 2010 to 2013, indicating that this subtype has become established in the European pig population. Finally, 13.9% of the viruses represented reassortants between these four lineages, especially between previous enzootic SIVs and H1N1pdm. These novel viruses were detected at the same time in several countries, with increasing prevalence. Some of them might become established in pig herds, causing implications for zoonotic infections. PMID:25542013

  17. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets

    NARCIS (Netherlands)

    ter Meulen, Jan; Bakker, Alexander B. H.; van den Brink, Edward N.; Weverling, Gerrit J.; Martina, Byron E. E.; Haagmans, Bart L.; Kuiken, Thijs; de Kruif, John; Preiser, Wolfgang; Spaan, Willy; Gelderblom, Hans R.; Goudsmit, Jaap; Osterhaus, Albert D. M. E.

    2004-01-01

    SARS coronavirus continues to cause sporadic cases of severe acute respiratory syndrome (SARS) in China. No active or passive immunoprophylaxis for disease induced by SARS coronavirus is available. We investigated prophylaxis of SARS coronavirus infection with a neutralising human monoclonal

  18. Measurement of Sinkhole Formation and Progression with InSAR

    Science.gov (United States)

    Jones, C. E.; Blom, R. G.

    2013-12-01

    The Bayou Corne Sinkhole initially formed in August 2012 from sidewall collapse of a brine cavern within the Napoleonville Salt Dome in southeastern Louisiana. The sinkhole, initially ~1 hectare in size, has expanded to ~10 hectare surface coverage by July 2013, as material continued to fill the subterranean void. Here we show that synthetic aperture radar (SAR) interferometry (InSAR) could have reliably forecast the formation and location of the Bayou Corne Sinkhole at least a month in advance from the large precursory surface deformation that occurred in the area where the sinkhole later formed. The Mississippi delta region has been imaged since 2009 using the NASA Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR), and radar data over the Napoleonville Salt Dome had been acquired on 2 July 2012, only a month before the sinkhole developed. Using radar interferometry, we show significant surface deformation of up to 250 mm occurred between 23 June 2011, and 2 July 2012, in an extended area encompassing the sinkhole site. The InSAR results show no measurable deformation prior to 23 June 2011. The measured precursory deformation pattern is consistent with compressive loading at the surface due to removal of support caused by a vertically oriented subsurface fracture. The measured strains relate directly to subsurface geology, salt rock properties, and internal stresses caused by the salt dome sidewall collapse. Measurements made with UAVSAR since the sinkhole formation, between August 2012 and July 2013, show progression of the surface deformation well beyond the limited extent of the sinkhole itself, with growth of the sinkhole following the direction of maximum surface deformation. These results show that even in radar-challenging environments such as the swamplands of Bayou Corne, L-band InSAR can be used to study the underlying geophysics of sinkhole formation and, furthermore, that InSAR data collected operationally for hazard monitoring could

  19. Investigation of ionospheric effects on SAR Interferometry (InSAR): A case study of Hong Kong

    Science.gov (United States)

    Zhu, Wu; Ding, Xiao-Li; Jung, Hyung-Sup; Zhang, Qin; Zhang, Bo-Chen; Qu, Wei

    2016-08-01

    Synthetic Aperture Radar Interferometry (InSAR) has demonstrated its potential for high-density spatial mapping of ground displacement associated with earthquakes, volcanoes, and other geologic processes. However, this technique may be affected by the ionosphere, which can result in the distortions of Synthetic Aperture Radar (SAR) images, phases, and polarization. Moreover, ionospheric effect has become and is becoming further significant with the increasing interest in low-frequency SAR systems, limiting the further development of InSAR technique. Although some research has been carried out, thorough analysis of ionospheric influence on true SAR imagery is still limited. Based on this background, this study performs a thorough investigation of ionospheric effect on InSAR through processing L-band ALOS-1/PALSAR-1 images and dual-frequency Global Positioning System (GPS) data over Hong Kong, where the phenomenon of ionospheric irregularities often occurs. The result shows that the small-scale ionospheric irregularities can cause the azimuth pixel shifts and phase advance errors on interferograms. Meanwhile, it is found that these two effects result in the stripe-shaped features in InSAR images. The direction of the stripe-shaped effects keep approximately constant in space for our InSAR dataset. Moreover, the GPS-derived rate of total electron content change index (ROTI), an index to reflect the level of ionospheric disturbances, may be a useful indicator for predicting the ionospheric effect for SAR images. This finding can help us evaluate the quality of SAR images when considering the ionospheric effect.

  20. Nano-SAR development for bioactivity of nanoparticles with considerations of decision boundaries.

    Science.gov (United States)

    Liu, Rong; Rallo, Robert; Weissleder, Ralph; Tassa, Carlos; Shaw, Stanley; Cohen, Yoram

    2013-05-27

    The development of classification nano-structure-activity Relationships (nano-SARs) of nanoparticle (NP) bioactivity is presented with the aim of demonstrating the integration of multiparametric toxicity/bioactivity assays to arrive at statistically meaningful class definitions (i.e., bioactivity/inactivity endpoints), as well as the implications of nano-SAR applicability domains and decision boundaries. Nano-SARs are constructed based on a dataset of 44 iron oxide core nanoparticles (NPs), used in molecular imaging and nano-sensing, containing bioactivity profiles for four cell types and four different assays. Class definitions are developed on the basis of 'hit' (i.e., significant bioactivity) identification analysis and self-organizing map based consensus clustering; these class definitions enable construction of nano-SARs of a high classification accuracy (>78%) with different NP descriptor combinations that include primary size, spin-lattice and spin-spin relaxivities, and zeta potentials. Analysis of the nano-SAR performance for different class definitions suggests that H4 (i.e., class with at least four hits) is a reasonable endpoint (from a 'regulatory' viewpoint) for keeping the level of false negatives (i.e., incorrect labeling of bioactive NPs as inactive) low. The establishment of a quantitative nano-SAR applicability domain is demonstrated, making use of a probability density with the H4 class definition and naive Bayesian classifier (NBC) model (with spin-lattice relaxivity and zeta potential as descriptors). Decision boundaries are determined for the above H4/NBC nano-SAR for different acceptance levels of false negative to false positive predictions, illustrating a practical approach that may assist in regulatory decision making with a consideration of reducing the likelihood of identifying bioactive NPs as being inactive. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. SAR processing in the cloud for oil detection in the Arctic

    Science.gov (United States)

    Garron, J.; Stoner, C.; Meyer, F. J.

    2016-12-01

    A new world of opportunity is being thawed from the ice of the Arctic, driven by decreased persistent Arctic sea-ice cover, increases in shipping, tourism, natural resource development. Tools that can automatically monitor key sea ice characteristics and potential oil spills are essential for safe passage in these changing waters. Synthetic aperture radar (SAR) data can be used to discriminate sea ice types and oil on the ocean surface and also for feature tracking. Additionally, SAR can image the earth through the night and most weather conditions. SAR data is volumetrically large and requires significant computing power to manipulate. Algorithms designed to identify key environmental features, like oil spills, in SAR imagery require secondary processing, and are computationally intensive, which can functionally limit their application in a real-time setting. Cloud processing is designed to manage big data and big data processing jobs by means of small cycles of off-site computations, eliminating up-front hardware costs. Pairing SAR data with cloud processing has allowed us to create and solidify a processing pipeline for SAR data products in the cloud to compare operational algorithms efficiency and effectiveness when run using an Alaska Satellite Facility (ASF) defined Amazon Machine Image (AMI). The products created from this secondary processing, were compared to determine which algorithm was most accurate in Arctic feature identification, and what operational conditions were required to produce the results on the ASF defined AMI. Results will be used to inform a series of recommendations to oil-spill response data managers and SAR users interested in expanding their analytical computing power.

  2. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein

    Science.gov (United States)

    McBride, Corrin E.; Machamer, Carolyn E.

    2010-01-01

    Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein, and may point to important differences in assembly and infectivity of these two coronaviruses. PMID:20580052

  3. TerraSAR-X StripMap Data Interpretation of Complex Urban Scenarios with 3D SAR Tomography

    Directory of Open Access Journals (Sweden)

    Lianhuan Wei

    2014-01-01

    Full Text Available The severe layover problem of complex urban scenarios in SAR data makes SAR data interpretation very difficult, especially for nonexperts. In this paper, we use 3D SAR tomography for SAR data interpretation of dense urban areas. An efficient and robust approach named Butterworth-filter based singular value decomposition (BSVD is used for tomographic analysis. Two typical dense urban areas of interest located in Shanghai are analyzed. The tomographic results could help users to better understand the backscattering scenario. The experimental results indicate that SAR tomography is a promising and effective way to facilitate SAR data interpretation of complex urban areas.

  4. Detecting Landscape Disturbance at the Nasca Lines Using SAR Data Collected from Airborne and Satellite Platforms

    Directory of Open Access Journals (Sweden)

    Douglas C. Comer

    2017-10-01

    Full Text Available We used synthetic aperture radar (SAR data collected over Peru’s Lines and Geoglyphs of the Nasca and Palpa World Heritage Site to detect and measure landscape disturbance threatening world-renowned archaeological features and ecosystems. We employed algorithms to calculate correlations between pairs of SAR returns, collected at different times, and generate correlation images. Landscape disturbances even on the scale of pedestrian travel are discernible in correlation images generated from airborne, L-band SAR. Correlation images derived from C-band SAR data collected by the European Space Agency’s Sentinel-1 satellites also provide detailed landscape change information. Because the two Sentinel-1 satellites together have a repeat pass interval that can be as short as six days, products derived from their data can not only provide information on the location and degree of ground disturbance, but also identify a time window of about one to three weeks during which disturbance must have occurred. For Sentinel-1, this does not depend on collecting data in fine-beam modes, which generally sacrifice the size of the area covered for a higher spatial resolution. We also report on pixel value stretching for a visual analysis of SAR data, quantitative assessment of landscape disturbance, and statistical testing for significant landscape change.

  5. Viruses in cancer treatment.

    Science.gov (United States)

    Alemany, R

    2013-03-01

    Soon after the discovery that viruses cause human disease, started the idea of using viruses to treat cancer. After the initial indiscriminate use, crude preparations of each novel virus in the early twentieth century, a second wave of virotherapy blossomed in the 60s with purified and selected viruses. Responses were rare and short-lived. Immune rejection of the oncolytic viruses was identified as the major problem and virotherapy was abandoned. During the past two decades virotherapy has re-emerged with engineered viruses, with a trend towards using them as tumor-debulking immunostimulatory agents combined with radio or chemotherapy. Currently, oncolytic Reovirus, Herpes, and Vaccinia virus are in late phase clinical trials. Despite the renewed hope, efficacy will require improving systemic tumor targeting, overcoming stroma barriers for virus spread, and selectively stimulating immune responses against tumor antigens but not against the virus. Virotherapy history, viruses, considerations for clinical trials, and hurdles are briefly overviewed.

  6. Completing the gaps in Kilauea's Father's Day InSAR displacement signature with ScanSAR

    Science.gov (United States)

    Bertran Ortiz, A.; Pepe, A.; Lanari, R.; Lundgren, P.; Rosen, P. A.

    2009-12-01

    Currently there are gaps in the known displacement signature obtained with InSAR at Kilauea between 2002 and 2009. InSAR data can be richer than GPS because of denser spatial cover. However, to better model rapidly varying and non-steady geophysical events InSAR is limited because of its less dense time observations of the area under study. The ScanSAR mode currently available in several satellites mitigates this effect because the satellite may illuminate a given area more than once within an orbit cycle. The Kilauea displacement graph below from Instituto per Il Rilevamento Electromagnetico dell'Ambiente (IREA) is a cut in space of the displacement signature obtained from a time series of several stripmap-to-stripmap interferograms. It shows that critical information is missing, especially between 2006 and 2007. The displacement is expected to be non-linear judging from the 2007-2008 displacement signature, thus simple interpolation would not suffice. The gap can be filled by incorporating Envisat stripmap-to-ScanSAR interferograms available during that time period. We propose leveraging JPL's new ROI-PAC ScanSAR module to create stripmap-to-ScanSAR interferograms. The new interferograms will be added to the stripmap ones in order to extend the existing stripmap time series generated by using the Small BAseline Subset (SBAS) technique. At AGU we will present denser graphs that better capture Kilauea's displacement between 2003 and 2009.

  7. Interspecies transmission of an H7N3 influenza virus from wild birds to intensively reared domestic poultry in Italy.

    Science.gov (United States)

    Campitelli, Laura; Mogavero, Elvira; De Marco, Maria Alessandra; Delogu, Mauro; Puzelli, Simona; Frezza, Fabiola; Facchini, Marzia; Chiapponi, Chiara; Foni, Emanuela; Cordioli, Paolo; Webby, Richard; Barigazzi, Giuseppe; Webster, Robert G; Donatelli, Isabella

    2004-05-20

    Since the "bird flu" incident in Hong Kong SAR in 1997, several studies have highlighted the substantial role of domestic birds, such as turkeys and chickens, in the ecology of influenza A viruses. Even if recent evidence suggests that chickens can maintain several influenza serotypes, avian influenza viruses (AIVs) circulating in domestic species are believed to be introduced each time from the wild bird reservoir. However, so far the direct precursor of influenza viruses from domestic birds has never been identified. In this report, we describe the antigenic and genetic characterization of the surface proteins of H7N3 viruses isolated from wild ducks in Italy in 2001 in comparison to H7N3 strains that circulated in Italian turkeys in 2002-2003. The wild and domestic avian strains appeared strictly related at both phenotypic and genetic level: homology percentages in seven of their genes were comprised between 99.8% (for PB2) and 99.1% (for M), and their NA genes differed mainly because of a 23-aminoacid deletion in the NA stalk. Outside this region of the molecule, the NAs of the two virus groups showed 99% similarity. These findings indicate that turkey H7N3 viruses were derived "in toto" from avian influenza strains circulating in wild waterfowl 1 year earlier, and represent an important step towards the comprehension of the mechanisms leading to interspecies transmission and emergence of potentially pandemic influenza viruses.

  8. METAPNEUMOVIRUS AND BOKAVIRUS RESPIRATORY INFECTIONS IN THE STRUCTURE OF SARS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    F. S. Harlamov

    2015-01-01

    Full Text Available The article provides an overview of the literature data about new pneumotropic viruses - metapneumovirus and bokavirus: taxonomy, structural features, pathogenesis, laboratory diagnosis, clinical symptoms of the diseases they cause and complications. The high incidence and bokavirus metapnevmovirus structure of SARS infections in preschool children, the authors have shown the example carried out at the Department of Infectious Diseases in Children Medical University (now RNIMU named after N.I. Pirogov and on the basis of clinical Institute of Virology, multicenter, randomized, blind, placebo-controlled study on the therapeutic efficacy and safety of interferon inducer Kagocel in 120 children aged 2 to 6 years. The findings to point out on significant reduction in the rate of relief of basic clinical manifestations of SARS, regardless of etiology, in children taking Kagocel in compare with a group of children who took a placebo.

  9. Verification of L-band SAR calibration

    Science.gov (United States)

    Larson, R. W.; Jackson, P. L.; Kasischke, E.

    1985-01-01

    Absolute calibration of a digital L-band SAR system to an accuracy of better than 3 dB has been verified. This was accomplished with a calibration signal generator that produces the phase history of a point target. This signal relates calibration values to various SAR data sets. Values of radar cross-section (RCS) of reference reflectors were obtained using a derived calibration relationship for the L-band channel on the ERIM/CCRS X-C-L SAR system. Calibrated RCS values were compared to known RCS values of each reference reflector for verification and to obtain an error estimate. The calibration was based on the radar response to 21 calibrated reference reflectors.

  10. Junction Point Detection Algorithm for SAR Image

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2013-01-01

    Full Text Available In this paper, we propose a novel junction point detector based on an azimuth consensus for remote sensing images. To eliminate the impact of noise and some noncorrelated edges of SAR image, an azimuth consensus constraint is developed. In addition to detecting the locations of junctions at the subpixel level, this operator recognizes their structures as well. A new formula that includes a minimization criterion for the total weighted distance is proposed to compute the locations of junction points accurately. Compared with other well-known detectors, including Forstner, JUDOCA, and CPDA, the experimental results indicate that our operator outperforms them both in location accuracy of junction points and in angle accuracy of branch edges. Moreover, our method possesses satisfying robustness to the impact of noise and changes of the SAR images. Our operator can be potentially used to solve a number of problems in computer vision, such as SAR image registration, wide-baseline matching, and UAV navigation system.

  11. Compact L-band SAR payload for UAV

    OpenAIRE

    Zaragoza Arbo, Josep

    2016-01-01

    Design and development of a Compact L-band SAR payload for UAV Design of a signal interference canceller due to the coupling between antennas for a SAR system. Diseño de un cancelador de señal interferente debido al acoplamiento entre antenas para un sistema SAR. Disseny d'un cancel·lador de senyal interferent degut a l'acoblament entre antenes per un sistema SAR.

  12. Fusion of synthetic aperture radiometer and noise waveform SAR images

    OpenAIRE

    Lukin, Konstantin A.; Kudriashov, V. V.

    2014-01-01

    Noise waveform SAR generates 2D SAR images of a scene. Advanced radiometric SAR imaging provides information on the objects thermal radiation, angular coordinates and even range. The brightness temperatures of rough and smooth surfaces are different. An active, noise waveform, operating mode of bistatic radiometer, based on antennae with beam synthesis, is considered with respect to the roughness criteria. The optimal and quasi-optimal algorithms for fusion of radiometric and SAR images are p...

  13. Use of Household Cluster Investigations to Identify Factors Associated with Chikungunya Virus Infection and Frequency of Case Reporting in Puerto Rico.

    Directory of Open Access Journals (Sweden)

    Danielle Bloch

    2016-10-01

    Full Text Available Chikungunya virus (CHIKV is transmitted by Aedes species mosquitoes and is the cause of an acute febrile illness characterized by potentially debilitating arthralgia. After emerging in the Caribbean in late 2013, the first locally-acquired case reported to public health authorities in Puerto Rico occurred in May 2014. During June-August 2014, household-based cluster investigations were conducted to identify factors associated with infection, development of disease, and case reporting.Residents of households within a 50-meter radius of the residence of laboratory-positive chikungunya cases that had been reported to Puerto Rico Department of Health (PRDH were offered participation in the investigation. Participants provided a serum specimen and answered a questionnaire that collected information on demographic factors, household characteristics, recent illnesses, healthcare seeking behaviors, and clinical diagnoses. Current CHIKV infection was identified by rRT-PCR, and recent CHIKV infection was defined by detection of either anti-CHIKV IgM or IgG antibody. Among 250 participants, 74 (30% had evidence of CHIKV infection, including 12 (5% with current and 62 (25% with recent CHIKV infection. All specimens from patients with CHIKV infection that were collected within four days, two weeks, and three weeks of illness onset were positive by RT-PCR, IgM ELISA, and IgG ELISA, respectively. Reporting an acute illness in the prior three months was strongly associated with CHIKV infection (adjusted odds ratio [aOR] = 21.6, 95% confidence interval [CI]: 9.24-50.3. Use of air conditioning (aOR = 0.50, 95% CI = 0.3-0.9 and citronella candles (aOR = 0.4, 95% CI = 0.1-0.9 were associated with protection from CHIKV infection. Multivariable analysis indicated that arthralgia (aOR = 51.8, 95% CI = 3.8-700.8 and skin rash (aOR = 14.2, 95% CI = 2.4-84.7 were strongly associated with CHIKV infection. Hierarchical cluster analysis of signs and symptoms reported by

  14. The Recent Severe Acute Respiratory Syndrome (SARS) Epidemic ...

    African Journals Online (AJOL)

    The symptoms of SARS are quite similar to those of common cold, malaria and respiratory tract infections all of which are common in our environment. SARS, being a new disease, has as yet neither a definite diagnostic test nor treatment. With the international transmission of SARS first reported in March 2003, it became ...

  15. (Q)SARs for human toxicological endpoints: a literature search

    NARCIS (Netherlands)

    Hulzebos E; Schielen P; Masilankiewicz L; CSR; NVIC

    1999-01-01

    The goal here was to describe human toxicological SARs (structure-activity relationships) available in the literature and used by the US EPA (Environmental Protection Agency). The CSR laboratory investigated implementation of SARs for the effect assessment. SARs correlate the molecular structure

  16. (Q)SARs for human toxicological endpoints: a literature search

    NARCIS (Netherlands)

    Hulzebos E; Schielen P; Masilankiewicz L; CSR; NVIC

    1999-01-01

    Het doel van dit rapport is het beschrijven van humaan toxicologische SARs (structuur-activiteitsrelaties) die beschikbaar zijn in de literatuur alsmede de SARs die gebruikt worden door de US EPA (Environmental Protection Agency). De implementatie van het gebruik van SARs voor de effect assessment

  17. Which preventive measures might protect health care workers from SARS?

    Directory of Open Access Journals (Sweden)

    Huang Jian

    2009-03-01

    Full Text Available Abstract Background Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS was observed among health care workers (HCWs during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective. Methods A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the "case group" and the "control group", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs. Results After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases. Conclusion Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.

  18. Estimating IMU heading error from SAR images.

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2009-03-01

    Angular orientation errors of the real antenna for Synthetic Aperture Radar (SAR) will manifest as undesired illumination gradients in SAR images. These gradients can be measured, and the pointing error can be calculated. This can be done for single images, but done more robustly using multi-image methods. Several methods are provided in this report. The pointing error can then be fed back to the navigation Kalman filter to correct for problematic heading (yaw) error drift. This can mitigate the need for uncomfortable and undesired IMU alignment maneuvers such as S-turns.

  19. Digital demodulator for wide bandwidth SAR

    DEFF Research Database (Denmark)

    Jørgensen, Jørn Hjelm

    2000-01-01

    A novel approach to the design of efficient digital quadrature demodulators for wide bandwidth SAR systems is described. Efficiency is obtained by setting the intermediate frequency to 1/4 the ADC sampling frequency. One channel is made filter-free by synchronizing the local oscillator with the o......A novel approach to the design of efficient digital quadrature demodulators for wide bandwidth SAR systems is described. Efficiency is obtained by setting the intermediate frequency to 1/4 the ADC sampling frequency. One channel is made filter-free by synchronizing the local oscillator...

  20. SAR clutter simulation with terrain effects

    Science.gov (United States)

    Greig, David W.; Scott, Iain

    2002-02-01

    A model for the signal returns from terrain features for a Synthetic Aperture Radar is developed. A standard range-azimuth geometry is used to divide the surface area into cells for which clutter returns are generated. This geometry is extended to a spherical Earth to introduce effects due to varying terrain height and slope, and to determine areas of shadow. The calculation of phase variation in the returned pulses at the IQ level required to successfully form a SAR is discussed. The technique is illustrated with an example which demonstrates the effect of look angle on SAR images.

  1. Geocoding of AIRSAR/TOPSAR SAR Data

    Science.gov (United States)

    Holecz, Francesco; Lou, Yun-Ling; vanZyl, Jakob

    1996-01-01

    It has been demonstrated and recognized that radar interferometry is a promising method for the determination of digital elevation information and terrain slope from Synthetic Aperture Radar (SAR) data. An important application of Interferometric SAR (InSAR) data in areas with topographic variations is that the derived elevation and slope can be directly used for the absolute radiometric calibration of the amplitude SAR data as well as for scattering mechanisms analysis. On the other hand polarimetric SAR data has long been recognized as permitting a more complete inference of natural surfaces than a single channel radar system. In fact, imaging polarimetry provides the measurement of the amplitude and relative phase of all transmit and receive polarizations. On board the NASA DC-8 aircraft, NASA/JPL operates the multifrequency (P, L and C bands) multipolarimetric radar AIRSAR. The TOPSAR, a special mode of the AIRSAR system, is able to collect single-pass interferometric C- and/or L-band VV polarized data. A possible configuration of the AIRSAR/TOPSAR system is to acquire single-pass interferometric data at C-band VV polarization and polarimetric radar data at the two other lower frequencies. The advantage of this system configuration is to get digital topography information at the same time the radar data is collected. The digital elevation information can therefore be used to correctly calibrate the SAR data. This step is directly included in the new AIRSAR Integrated Processor. This processor uses a modification of the full motion compensation algorithm described by Madsen et al. (1993). However, the Digital Elevation Model (DEM) with the additional products such as local incidence angle map, and the SAR data are in a geometry which is not convenient, since especially DEMs must be referred to a specific cartographic reference system. Furthermore, geocoding of SAR data is important for multisensor and/or multitemporal purposes. In this paper, a procedure to

  2. Automatic Transfer of SAR Patterns for AUXSAR

    Science.gov (United States)

    2015-10-01

    RB M RB S)− - , - − CG HC-130J, MH-65, MH-60T (PFPS) − CG GCCS .ovl for Mission Suite/Pallet (HU-144/130J) − Cutter VEGA (ECS/ECDIS) − Garmin Flight...rom • GoogleEarth /eGIS .kml (pattern name) ( S CG Ai f )• .xml PFP : Large rcra t • .fpl ( Garmin Flight Plan: G1000 etc) • .txt (ForeFlight) • .sar...Transfer of SAR Patterns for AUXSAR| RDC Mr. Sean Lester | CG-761| Oct 2015 17 AUXSAR Field Test– Garmin GPSmap 496 In Flight 7/8/2016

  3. Science data collection with polarimetric SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Woelders, Kim; Madsen, Søren Nørvang

    1996-01-01

    Discusses examples on the use of polarimetric SAR in a number of Earth science studies. The studies are presently being conducted by the Danish Center for Remote Sensing. A few studies of the European Space Agency's EMAC programme are also discussed. The Earth science objectives are presented......, and the potential of polarimetric SAR is discussed and illustrated with data collected by the Danish airborne EMISAR system during a number of experiments in 1994 and 1995. The presentation will include samples of data acquired for the different studies...

  4. Utility of Characterizing and Monitoring Suspected Underground Nuclear Sites with VideoSAR

    Science.gov (United States)

    Dauphin, S. M.; Yocky, D. A.; Riley, R.; Calloway, T. M.; Wahl, D. E.

    2016-12-01

    Sandia National Laboratories proposed using airborne synthetic aperture RADAR (SAR) collected in VideoSAR mode to characterize the Underground Nuclear Explosion Signature Experiment (UNESE) test bed site at the Nevada National Security Site (NNSS). The SNL SAR collected airborne, Ku-band (16.8 GHz center frequency), 0.2032 meter ground resolution over NNSS in August 2014 and X-band (9.6 GHz), 0.1016 meter ground resolution fully-polarimetric SAR in April 2015. This paper reports the findings of processing and exploiting VideoSAR for creating digital elevation maps, detecting cultural artifacts and exploiting full-circle polarimetric signatures. VideoSAR collects a continuous circle of phase history data, therefore, imagery can be formed over the 360-degrees of the site. Since the Ku-band VideoSAR had two antennas suitable for interferometric digital elevation mapping (DEM), DEMs could be generated over numerous aspect angles, filling in holes created by targets with height by imaging from all sides. Also, since the X-band VideoSAR was fully-polarimetric, scattering signatures could be gleaned from all angles also. Both of these collections can be used to find man-made objects and changes in elevation that might indicate testing activities. VideoSAR provides a unique, coherent measure of ground objects allowing one to create accurate DEMS, locate man-made objects, and identify scattering signatures via polarimetric exploitation. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. The authors would like to thank the National Nuclear Security Administration, Defense Nuclear Nonproliferation Research and Development, for sponsoring this work. We would also like to thank the Underground Nuclear Explosion Signatures Experiment team, a multi

  5. AraC-Type Regulator Rbf Controls the Staphylococcus epidermidis Biofilm Phenotype by Negatively Regulating the icaADBC Repressor SarR.

    Science.gov (United States)

    Rowe, Sarah E; Campbell, Christopher; Lowry, Colm; O'Donnell, Sinead T; Olson, Michael E; Lindgren, Jill K; Waters, Elaine M; Fey, Paul D; O'Gara, James P

    2016-11-01

    Regulation of icaADBC-encoded polysaccharide intercellular adhesin (PIA)/poly-N-acetylglucosasmine (PNAG) production in staphylococci plays an important role in biofilm-associated medical-device-related infections. Here, we report that the AraC-type transcriptional regulator Rbf activates icaADBC operon transcription and PIA production in Staphylococcus epidermidis Purified recombinant Rbf did not bind to the ica operon promoter region in electrophoretic mobility shift assays (EMSAs), indicating that Rbf regulates ica transcription indirectly. To identify the putative transcription factor(s) involved in Rbf-mediated icaADBC regulation, the ability of recombinant Rbf to interact with the promoter sequences of known icaADBC regulators was investigated. Recombinant Rbf bound to the sarR promoter and not the sarX, sarA, sarZ, spx, and srrA promoters. Reverse transcription (RT)-PCR demonstrated that Rbf acts as a repressor of sarR transcription. PIA expression and biofilm production were restored to wild-type levels in an rbf sarR double mutant grown in brain heart infusion (BHI) medium supplemented with NaCl, which is known to activate the ica locus, but not in BHI medium alone. RT-PCR further demonstrated that although Rbf does not bind the sarX promoter, it nevertheless exerted a negative effect on sarX expression. Apparently, direct downregulation of the SarR repressor by Rbf has a dominant effect over indirect repression of the SarX activator by Rbf in the control of S. epidermidis PIA production and biofilm formation. The importance of Staphylococcus epidermidis as an opportunistic pathogen in hospital patients with implanted medical devices derives largely from its capacity to form biofilm. Expression of the icaADBC-encoded extracellular polysaccharide is the predominant biofilm mechanism in S. epidermidis clinical isolates and is tightly regulated. Here, we report that the transcriptional regulator Rbf promotes icaADBC expression by negatively regulating

  6. Enhanced SAR data processing for land instability forecast.

    Science.gov (United States)

    Argentiero, Ilenia; Pellicani, Roberta; Spilotro, Giuseppe; Parisi, Alessandro; Bovenga, Fabio; Pasquariello, Guido; Refice, Alberto; Nutricato, Raffaele; Nitti, Davide Oscar; Chiaradia, Maria Teresa

    2017-04-01

    Monitoring represents the main tool for carrying out evaluation procedures and criteria for spatial and temporal landslide forecast. The forecast of landslide behaviour depends on the possibility to identify either evidences of activity (displacement, velocity, volume of unstable mass, direction of displacement, and their temporal variation) or triggering parameters (rainfalls). Generally, traditional geotechnical landslide monitoring technologies permit to define, if correctly positioned and with adequate accuracy, the critical value of displacement and/or acceleration into landslide body. In most cases, they do not allow real time warning signs to be generated, due to environmental induced errors, and the information is related to few points on unstable area. Remote-sensing monitoring instruments are capable of inspecting an unstable slope with high spatial and temporal frequency, but allow solely measurements of superficial displacements and deformations. Among these latest technologies, the satellite Persistent Scatterer SAR Interferometry (PSInSAR) is very useful to investigate the unstable area both in terms of space and time. Indeed, this technique allows to analyse wide areas, individuate critical unstable areas, not identifiable by means detailed in situ surveys, and study the phenomenon evolution in a long time-scale. Although this technique usually adopts, as first approximation, a linear model to describe the displacement of the detected targets, also non-linear models can be used. However, the satellite revisit time, which defines the time sampling of the detected displacement signal, limits the maximum measurable velocity and acceleration. This makes it difficult to assess in the short time any acceleration indicating a loss of equilibrium and, therefore, a probable reactivation of the landslide. The recent Sentinel-1 mission from the European Space Agency (ESA), provides a spatial resolution comparable to the previous ESA missions, but a nominal

  7. Substitution at aspartic acid 1128 in the SARS coronavirus spike glycoprotein mediates escape from a S2 domain-targeting neutralizing monoclonal antibody.

    Science.gov (United States)

    Ng, Oi-Wing; Keng, Choong-Tat; Leung, Cynthia Sau-Wai; Peiris, J S Malik; Poon, Leo Lit Man; Tan, Yee-Joo

    2014-01-01

    The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine monoclonal antibodies (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection in vitro (Lip KM et al, J Virol. 2006 Jan; 80(2): 941-50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S protein at a novel epitope within the S2 subunit at amino acids 1111-1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.

  8. SARS knowledge, perceptions, and behaviors: a comparison between Finns and the Dutch during the SARS outbreak in 2003

    NARCIS (Netherlands)

    Vartti, A.M.; Oenema, A.; Schreck, M.; Uutela, A.; Zwart, de O.; Brug, J.; Aro, A.R.

    2009-01-01

    BACKGROUND: The SARS outbreak served to test both local and international outbreak management and risk communication practices. PURPOSE: The study compares SARS knowledge, perceptions, behaviors, and information between Finns and the Dutch during the SARS outbreak in 2003. METHOD: The participants

  9. An Inflatable L-Band Microstrip SAR Array

    Science.gov (United States)

    Huang, J.; Lou, M.; Feria, A.; Kim, Y.

    1998-01-01

    Inflatable structures have been identified as one of the enabling technologies to achieve low mass, high packaging efficiency, and reliable deployment for future NASA spaceborne synthetic aperture radar (SAR) array antennas. A current L-band SAR antenna development, with aperture size of 10 m x 3 m, is required to have the capabilities of dual-linear polarization, 80-MHz bandwidth, electronic beam scanning, and less than 100 kg of mass. An inflatable concept, which employs the inflatable tubular frame structure to support a multilayer, thin membrane, microstrip array radiating aperture, has been identified. It uses a "roll-up" concept, for deploying the thin membranes to form a planar array aperture. To demonstrate this concept, two contracts were independently given to ILC Dover, Inc. and L'Garde Corp. for each to construct a 1/3 size (3.3 m x 1.0 m) functional model with an inflatable structure at L-band frequency. JPL provided both contractors with the antenna RF design and the etched thin membranes. The ILC Dover model has been delivered to JPL and gone through a series of deployment and RF tests. This is believed to be the first inflatable array antenna ever developed. This paper presents the mechanical and electrical constructions of this inflatable array and its test results.

  10. A set of host proteins interacting with papaya ringspot virus NIa-Pro protein identified in a yeast two-hybrid system.

    Science.gov (United States)

    Gao, L; Shen, W T; Yan, P; Tuo, D C; Li, X Y; Zhou, P

    2012-01-01

    The protein-protein interactions between viral and host proteins play an essential role in plant virus infection and host defense. The potyviral nuclear inclusion protein a protease (NIa-Pro) is involved in various steps of viral infection. In this study, the host proteins interacting with papaya ringspot virus (PRSV) NIa-Pro were screened in a Carica papaya L. plant cDNA library using a Sos recruitment two-hybrid system (SRS). We confirmed that the full-length EIF3G, FBPA1, FK506BP, GTPBP, MSRB1, and MTL from papaya can interact specifically with PRSV NIa-Pro in yeast, respectively. These proteins fufill important functions in plant protein translation, biotic and abiotic stress, energy metabolism and signal transduction. In this paper, we discuss possible functions of interactions between these host proteins and NIa-Pro in PRSV infection and their role in host defense. Sos recruitment two-hybrid system; papaya ringspot virus; NIa-Pro; protein-protein interaction.

  11. Calibration Results for J-ERS-1 SAR Data Produced by the Alaska SAR Facility

    Science.gov (United States)

    Freeman, A.; Alves, M.; Williams, J.

    1993-01-01

    The Alaska SAR Facility has been receiving and processing SAR data from the J-ERS-1 satellite since Spring 1992. Corner reflectors have been set up for J-ERS-1 SAR calibration at a site near Delta Junction, in central Alaska. Image quality and calibration analysis results from the Delta Junction site and others will be presented in this paper. The impact of the 3-bit Analog-to-Digital Converter and the automatic stepping of the gain as a function of range in the J-ERS-1 radar receiver on calibration performance has been assessed. Preliminary observations on J-ERS-1 SAR data are that the average Signal-to-Noise ratio is generally fairly low, in the range 5-6 dB. Azimuth ambiguity levels are higher than preflight analysis indicated. Over land, the dynamic range in the backscatter at L-band for approximately 36 degree incidence angle is often fairly high...

  12. Quantum-SAR Extension of the Spectral-SAR Algorithm. Application to Polyphenolic Anticancer Bioactivity

    Directory of Open Access Journals (Sweden)

    Adrian Chiriac

    2009-03-01

    Full Text Available Aiming to assess the role of individual molecular structures in the molecular mechanism of ligand-receptor interaction correlation analysis, the recent Spectral-SAR approach is employed to introduce the Quantum-SAR (QuaSAR “wave” and “conversion factor” in terms of difference between inter-endpoint inter-molecular activities for a given set of compounds; this may account for inter-conversion (metabolization of molecular (concentration effects while indicating the structural (quantum based influential/detrimental role on bio-/eco- effect in a causal manner rather than by simple inspection of measured values; the introduced QuaSAR method is then illustrated for a study of the activity of a series of flavonoids on breast cancer resistance protein.

  13. TomoSAR Platform: The New Irstea Service as Demand for SAR, Interferometry, Polarimetry and Tomography

    Science.gov (United States)

    Ho Tong Minh, Dinh; Ngo, Yen-Nhi; Baghdadi, Nicolas; Maurel, Pierre

    2016-08-01

    Developing and improving methods to monitor both natural and non-natural environments such as forest and urban in space and time is a timely challenge. To overcome this challenge, we created a software platform - TomoSAR. The kernel of this platform supports the entire processing from SAR, Interferometry, Polarimetry, to Tomography (so called TomoSAR). The objective of this paper is to introduce this platform about its design architecture and its capacity. We showed four examples to highlight the TomoSAR platform capacities. First, the useful of the interferometric coherence of TOPS Sentinel-1 for land cover classification was highlighted. Second, a TOPS Sentinel-1 differential interferogram in a complex scenario volcano was successfully produced. Third, a TOPS Persistent Scatterers Interferometry analysis for estimating subsidence in Ho Chi Minh City area was demonstrated. Finally, the capability of processing and modelling of 3D P-band tomography in volume forest scattering were reported.

  14. Involvement of ethylene in lesion development and systemic acquired resistance in tobacco during the hypersensitive reaction to tobacco mosaic virus

    NARCIS (Netherlands)

    Knoester, M.; Linthorst, H.J.M.; Bol, J.F.; Loon, L.C. van

    2001-01-01

    Different approaches were taken to investigate the significance of ethylene in lesion development and systemic acquired resistance (SAR) in tobacco (Nicotiana tabacum) reacting hypersensitively to tobacco mosaic virus (TMV). Gaseous ethylene, the ethylene precursor 1-aminocyclopropane-1-carboxylic

  15. InSAR imagery pattern matching validation for landslide assessment

    Science.gov (United States)

    Serbulea, Manole-Stelian; Gogu, Radu; Teleaga, Delia; Marcel Manoli, Daniel; Priceputu, Adrian; Gaitanaru, Dragos Stefan; Ungureanu, Constantin; Anghel, Alexandra; Andronic, Adrian; Niculescu, Alexandru; Liviu Bugea, Adrian

    2013-04-01

    The need for identifying over large areas ongoing instability phenomena and spotting the old ones pushed the boundaries of geotechnical engineering from numerical modeling and point-wise in-situ measurements towards geodesic and geographic sciences. Regardless of the ground-based monitoring techniques' precision and reliability, a larger scale monitoring is often useful to either better correlate the scattered results or to identify additional monitoring points. Using aerial ortho-photogrammetry and site visit recognition represent a good, yet costly method to obtain qualitative information about old inactive landslides. A more suitable approach is using ground-based or satellite radar interferometry (InSAR). The obvious disadvantage of the ground-based system is that the monitoring has to be carried out on a predetermined site while the space-borne system may be set to collect information from various sites in range by each successive passing. The quantitative results acquired through the means of InSAR provide a precise set of information regarding the soil surface displacement, with high accuracy and reliability. They provide a great means of identifying danger zones as well as a way of calibrating and augmenting the classical monitoring techniques. This work describes the possibility of integrating the InSAR measurements with the ground monitoring techniques to identify landslide occurrence hazard and reveal the whole of affected areas even when minute symptoms develop. One of the objectives is to propose InSAR monitoring as a fast and efficient mapping tool to help authorities minimize the damage produced by landslides. It can also provide engineers and scientists additional information to further study landslides dynamics phenomena (such as propagation). Interferometry on SAR data uses phase values from two radar images. When a point changes position, the distance between it and the sensor alters, modifying the phase of the signal. This change is used to

  16. Multiplier-free filters for wideband SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Christensen, Erik Lintz

    2001-01-01

    This paper derives a set of parameters to be optimized when designing filters for digital demodulation and range prefiltering in SAR systems. Aiming at an implementation in field programmable gate arrays (FPGAs), an approach for the design of multiplier-free filters is outlined. Design results...

  17. Epidemic Models for SARS and Measles

    Science.gov (United States)

    Rozema, Edward

    2007-01-01

    Recent events have led to an increased interest in emerging infectious diseases. This article applies various deterministic models to the SARS epidemic of 2003 and a measles outbreak in the Netherlands in 1999-2000. We take a historical approach beginning with the well-known logistic curve and a lesser-known extension popularized by Pearl and Reed…

  18. What is Gammarus campylops of Sars, 1894

    NARCIS (Netherlands)

    Stock, J.H.; Kant, P.

    1966-01-01

    A revision of the specimens described by Sars, 1894, as Gammarus campylops Leach, 1814, proved that they did not belong to that species, nor to Gammarus ochlos Reid, 1945 (= G. sarsi Reid, 1943), as Reid believed. Reid’s species, of which also original specimens have been reexamined, is identical

  19. SAR-sensing of vegetation wetness

    NARCIS (Netherlands)

    de Jong, JJM; Klaassen, W

    1998-01-01

    The goal of this study is to measure rain induced forest canopy wetness. The approach used is ERS tandem mission C-band SAR backscatter change detection between successive dry and rainy days. The observed backscatter change is positively related with modelled canopy wetness change. It is therefore

  20. Matrix approach to modelling of SAR signals

    NARCIS (Netherlands)

    Lidicky, L.; Hoogeboom, P.

    2005-01-01

    The paper presents a matrix approach to implementation of SAR signal generating and processing schemes. This approach is advantageous when matrix oriented software such as Matlab is used. Algorithms written in this type of software packages run faster compared to the same algorithms written for the

  1. Citizens’ Health Information Behaviors During SARS Spread Periods in Taiwan

    Directory of Open Access Journals (Sweden)

    Nei-Ching Yeh

    2003-09-01

    Full Text Available The purpose of this study is to investigate the information behaviors of citizens during the periods of SARS spreading in Taiwan. This study is exploratory in nature, and the naturalistic inquiry approach was applied. Sixteen persons, aged from 20 to 62 years old, were interviewed in order to understand their primary information channels of obtaining SARS information, the characteristics of information communication, the methods of infection, the attitudes toward SARS news, and the influences of SARS to life. The findings show that most participants obtained SARS information from televisions. SARS became the major topic of chatting between people, but telephone communication replaced face to face communication. Part of interviewers applied folk medicine to guard against SARS. Participant dissatisfied that governments did not announce much more authoritative information. The results also found participants’ information sharing and information avoidance behaviors.[Article content in Chinese

  2. SAR Raw Data Generation for Complex Airport Scenes

    Directory of Open Access Journals (Sweden)

    Jia Li

    2014-10-01

    Full Text Available The method of generating the SAR raw data of complex airport scenes is studied in this paper. A formulation of the SAR raw signal model of airport scenes is given. Via generating the echoes from the background, aircrafts and buildings, respectively, the SAR raw data of the unified SAR imaging geometry is obtained from their vector additions. The multipath scattering and the shadowing between the background and different ground covers of standing airplanes and buildings are analyzed. Based on the scattering characteristics, coupling scattering models and SAR raw data models of different targets are given, respectively. A procedure is given to generate the SAR raw data of airport scenes. The SAR images from the simulated raw data demonstrate the validity of the proposed method.

  3. e-Collaboration for Earth observation (E-CEO): the Cloud4SAR interferometry data challenge

    Science.gov (United States)

    Casu, Francesco; Manunta, Michele; Boissier, Enguerran; Brito, Fabrice; Aas, Christina; Lavender, Samantha; Ribeiro, Rita; Farres, Jordi

    2014-05-01

    The e-Collaboration for Earth Observation (E-CEO) project addresses the technologies and architectures needed to provide a collaborative research Platform for automating data mining and processing, and information extraction experiments. The Platform serves for the implementation of Data Challenge Contests focusing on Information Extraction for Earth Observations (EO) applications. The possibility to implement multiple processors within a Common Software Environment facilitates the validation, evaluation and transparent peer comparison among different methodologies, which is one of the main requirements rose by scientists who develop algorithms in the EO field. In this scenario, we set up a Data Challenge, referred to as Cloud4SAR (http://wiki.services.eoportal.org/tiki-index.php?page=ECEO), to foster the deployment of Interferometric SAR (InSAR) processing chains within a Cloud Computing platform. While a large variety of InSAR processing software tools are available, they require a high level of expertise and a complex user interaction to be effectively run. Computing a co-seismic interferogram or a 20-years deformation time series on a volcanic area are not easy tasks to be performed in a fully unsupervised way and/or in very short time (hours or less). Benefiting from ESA's E-CEO platform, participants can optimise algorithms on a Virtual Sandbox environment without being expert programmers, and compute results on high performing Cloud platforms. Cloud4SAR requires solving a relatively easy InSAR problem by trying to maximize the exploitation of the processing capabilities provided by a Cloud Computing infrastructure. The proposed challenge offers two different frameworks, each dedicated to participants with different skills, identified as Beginners and Experts. For both of them, the contest mainly resides in the degree of automation of the deployed algorithms, no matter which one is used, as well as in the capability of taking effective benefit from a parallel

  4. Ice Freeze-up and Break-up Detection of Shallow Lakes in Northern Alaska with Spaceborne SAR

    Directory of Open Access Journals (Sweden)

    Cristina M. Surdu

    2015-05-01

    Full Text Available Shallow lakes, with depths less than ca. 3.5–4 m, are a ubiquitous feature of the Arctic Alaskan Coastal Plain, covering up to 40% of the land surface. With such an extended areal coverage, lakes and their ice regimes represent an important component of the cryosphere. The duration of the ice season has major implications for the regional and local climate, as well as for the physical and biogeochemical processes of the lakes. With day and night observations in all weather conditions, synthetic aperture radar (SAR sensors provide year-round acquisitions. Monitoring the evolution of radar backscatter (σ° is useful for detecting the timing of the beginning and end of the ice season. Analysis of the temporal evolution of C-band σ° from Advanced Synthetic Aperture Radar (ASAR Wide Swath and RADARSAT-2 ScanSAR, with a combined frequency of acquisitions from two to five days, was employed to evaluate the potential of SAR to detect the timing of key lake-ice events. SAR observations from 2005 to 2011 were compared to outputs of the Canadian Lake Ice Model (CLIMo. Model simulations fall within similar ranges with those of the SAR observations, with a mean difference between SAR observations and model simulations of only one day for water-clear-of-ice (WCI from 2006 to 2010. For freeze onset (FO, larger mean differences were observed. SAR analysis shows that the mean FO date for these shallow coastal lakes is 30 September and the mean WCI date is 5 July. Results reveal that greater variability existed in the mean FO date (up to 26 days than in that of melt onset (MO (up to 12 days and in that of WCI (6 days. Additionally, this study also identifies limitations and provides recommendations for future work using C-band SAR for monitoring the lake- ice phenology of shallow Arctic lakes.

  5. A Hierarchical Multi-Temporal InSAR Method for Increasing the Spatial Density of Deformation Measurements

    Directory of Open Access Journals (Sweden)

    Tao Li

    2014-04-01

    Full Text Available Point-like targets are useful in providing surface deformation with the time series of synthetic aperture radar (SAR images using the multi-temporal interferometric synthetic aperture radar (MTInSAR methodology. However, the spatial density of point-like targets is low, especially in non-urban areas. In this paper, a hierarchical MTInSAR method is proposed to increase the spatial density of deformation measurements by tracking both the point-like targets and the distributed targets with the temporal steadiness of radar backscattering. To efficiently reduce error propagation, the deformation rates on point-like targets with lower amplitude dispersion index values are first estimated using a least squared estimator and a region growing method. Afterwards, the distributed targets are identified using the amplitude dispersion index and a Pearson correlation coefficient through a multi-level processing strategy. Meanwhile, the deformation rates on distributed targets are estimated during the multi-level processing. The proposed MTInSAR method has been tested for subsidence detection over a suburban area located in Tianjin, China using 40 high-resolution TerraSAR-X images acquired between 2009 and 2010, and validated using the ground-based leveling measurements. The experiment results indicate that the spatial density of deformation measurements can be increased by about 250% and that subsidence accuracy can reach to the millimeter level by using the hierarchical MTInSAR method.

  6. Multisensor analysis of hydrologic features in the Wind River Range, Wyoming with emphasis on the SEASAT SAR

    Science.gov (United States)

    Foster, J. L.; Hall, D. K. (Principal Investigator)

    1979-01-01

    The author has identified the following significant results. Analysis of imagery obtained over west-central Wyoming indicates that Seasat SAR has capability for hydrologic mapping. Both the L-Band (Seasat) and the X-Band (aircraft) SAR imagery were useful for observing drainage detail. Streams have bright signatures on the SAR imagery because the riparian vegetation produces a rough surface and thus high radar returns. Lakes appear relatively bright on the Seasat image presumably in response to surface ripples and waves induced by wind action. SAR imagery did not reveal snow at either the 23.5 cm (L-Band) or 2.8 cm (X-Band) wavelengths. Comparing Seasat and X-Band aircraft SAR imagery to LANDSAT RBV imagery, U-2 photography, and topographic maps of the Wind River Range, it appears that the SAR data do not seem to provide as much hydrologic information as do the other sensors in the visible and near infrared portions of the spectrum.

  7. Sequence variation of the glycoprotein gene identifies three distinct lineages within field isolates of viral hemorrhagic septicemia virus, a fish rhabdovirus

    Science.gov (United States)

    Benmansour, A.; Bascuro, B.; Monnier, A.F.; Vende, P.; Winton, J.R.; de Kinkelin, P.

    1997-01-01

    To evaluate the genetic diversity of viral haemorrhagic septicaemia virus (VHSV), the sequence of the glycoprotein genes (G) of 11 North American and European isolates were determined. Comparison with the G protein of representative members of the family Rhabdoviridae suggested that VHSV was a different virus species from infectious haemorrhagic necrosis virus (IHNV) and Hirame rhabdovirus (HIRRV). At a higher taxonomic level, VHSV, IHNV and HIRRV formed a group which was genetically closest to the genus Lyssavirus. Compared with each other, the G genes of VHSV displayed a dissimilar overall genetic diversity which correlated with differences in geographical origin. The multiple sequence alignment of the complete G protein, showed that the divergent positions were not uniformly distributed along the sequence. A central region (amino acid position 245-300) accumulated substitutions and appeared to be highly variable. The genetic heterogeneity within a single isolate was high, with an apparent internal mutation frequency of 1.2 x 10(-3) per nucleotide site, attesting the quasispecies nature of the viral population. The phylogeny separated VHSV strains according to the major geographical area of isolation: genotype I for continental Europe, genotype II for the British Isles, and genotype III for North America. Isolates from continental Europe exhibited the highest genetic variability, with sub-groups correlated partially with the serological classification. Neither neutralizing polyclonal sera, nor monoclonal antibodies, were able to discriminate between the genotypes. The overall structure of the phylogenetic tree suggests that VHSV genetic diversity and evolution fit within the model of random change and positive selection operating on quasispecies.

  8. Combination of Conventional and Advanced DInSAR to Monitor Very Fast Mining Subsidence with TerraSAR-X Data: Bytom City (Poland

    Directory of Open Access Journals (Sweden)

    Maria Przyłucka

    2015-04-01

    Full Text Available In this work, the analysis of TerraSAR-X satellite images combining both conventional and advanced Differential Synthetic Aperture Radar Interferometry (DInSAR approaches has proven to be effective to detect and monitor fast evolving mining subsidence on urban areas in the Upper Silesian Coal Basin (Poland. This region accounts for almost three million inhabitants where mining subsidence has produced severe damage to urban structures and infrastructures in recent years. Conventional DInSAR approach was used to generate 28 differential interferograms between 5 July 2011 and 21 June 2012 identifying 31 subsidence troughs that account up to 245 mm of displacement in 54 days (equivalent to 1660 mm/year. SqueeSARTM processing yielded a very dense measurement point distribution, failing to detect faster displacements than 330 mm/year, which occur within the subsidence troughs detected with conventional DInSAR. Despite this limitation, this approach was useful to delimit stable areas where mining activities are not conducted and areas affected by residual subsidence surrounding the detected subsidence troughs. These residual subsidence mining areas are located approximately 1 km away from the 31 detected subsidence troughs and account for a subsidence rate greater than 17 mm/year on average. The validation of this methodology has been performed over Bytom City were underground mining activity produced severe damages in August 2011. Conventional DInSAR permitted to successfully map subsidence troughs between July and August 2011 that coincide spatially and temporally with the evolution of underground mining excavations, as well as with the demolition of 28 buildings of Karb district. Additionally, SqueeSARTM displacement estimates were useful to delimit an area of 8.3 km2 of Bytom city that is affected by a residual mining subsidence greater than 5 mm/year and could potentially suffer damages in the midterm. The comparison between geodetic data and

  9. Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway.

    Science.gov (United States)

    Sui, Jianhua; Aird, Daniel R; Tamin, Azaibi; Murakami, Akikazu; Yan, Meiying; Yammanuru, Anuradha; Jing, Huaiqi; Kan, Biao; Liu, Xin; Zhu, Quan; Yuan, Qing-An; Adams, Gregory P; Bellini, William J; Xu, Jianguo; Anderson, Larry J; Marasco, Wayne A

    2008-11-01

    Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs) in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs) with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID) "hot spot" in a light chain CDR (complementarity determining region) alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM) of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural information in

  10. Change classification in SAR time series: a functional approach

    Science.gov (United States)

    Boldt, Markus; Thiele, Antje; Schulz, Karsten; Hinz, Stefan

    2017-10-01

    Change detection represents a broad field of research in SAR remote sensing, consisting of many different approaches. Besides the simple recognition of change areas, the analysis of type, category or class of the change areas is at least as important for creating a comprehensive result. Conventional strategies for change classification are based on supervised or unsupervised landuse / landcover classifications. The main drawback of such approaches is that the quality of the classification result directly depends on the selection of training and reference data. Additionally, supervised processing methods require an experienced operator who capably selects the training samples. This training step is not necessary when using unsupervised strategies, but nevertheless meaningful reference data must be available for identifying the resulting classes. Consequently, an experienced operator is indispensable. In this study, an innovative concept for the classification of changes in SAR time series data is proposed. Regarding the drawbacks of traditional strategies given above, it copes without using any training data. Moreover, the method can be applied by an operator, who does not have detailed knowledge about the available scenery yet. This knowledge is provided by the algorithm. The final step of the procedure, which main aspect is given by the iterative optimization of an initial class scheme with respect to the categorized change objects, is represented by the classification of these objects to the finally resulting classes. This assignment step is subject of this paper.

  11. Classification NanoSAR development for cytotoxicity of metal oxide nanoparticles.

    Science.gov (United States)

    Liu, Rong; Rallo, Robert; George, Saji; Ji, Zhaoxia; Nair, Sumitra; Nel, André E; Cohen, Yoram

    2011-04-18

    A classification-based cytotoxicity nanostructure-activity relationship (nanoSAR) is presented based on a set of nine metal oxide nanoparticles to which transformed bronchial epithelial cells (BEAS-2B) were exposed over a range of concentrations (0.375-200 mg L(-1) ) and exposure times up to 24 h. The nanoSAR is developed using cytotoxicity data from a high-throughput screening assay that was processed to identify and label toxic (in terms of the propidium iodide uptake of BEAS-2B cells) versus nontoxic events relative to an unexposed control cell population. Starting with a set of fourteen intuitive but fundamental physicochemical nanoSAR input parameters, a number of models were identified which had a classification accuracy above 95%. The best-performing model had a 100% classification accuracy in both internal and external validations. This model is based on three descriptors: atomization energy of the metal oxide, period of the nanoparticle metal, and nanoparticle primary size, in addition to nanoparticle volume fraction (in solution). Notwithstanding the success of the present modeling approach with a relatively small nanoparticle library, it is important to recognize that a significantly larger data set would be needed in order to expand the applicability domain and increase the confidence and reliability of data-driven nanoSARs. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Classification Nano-SAR Development for Cytotoxicity of Metal Oxide Nanoparticles

    Science.gov (United States)

    Liu, Rong; Rallo, Robert; George, Saji; Ji, Zhaoxia; Nair, Sumitra; Nel, André E.

    2014-01-01

    A classification based cytotoxicity nano-structure-activity-realtionship (nano-SAR) is presented based on a set of nine metal oxide nanoparticles to which transformed bronchial epithelial cells (BEAS-2B) were exposed over a range of concentrations of 0.375–200 mg·L−1 and exposure times up to 24 h. The nano-SAR is developed using cytotoxicity data from high throughput screening (HTS) assay that was processed to identify and label toxic (in terms of the Propidium Iodide uptake of BEAS-2B cells) versus non-toxic events relative to unexposed control cell population. Starting with a set of fourteen intuitive but fundamental physicochemical nano-SAR input parameters, a number of models were identified which had classification accuracy above 95%. The best performing model had a 100% classification accuracy in both internal and external validation. This model is based on four descriptors including the atomization energy of the metal oxide, period of the nanoparticle metal, nanoparticle primary size, in addition to nanoparticle volume fraction (in solution). Notwithstanding the success of the present modeling approach with a relatively small nanoparticle library, it is important to recognize that a significantly larger data set would be needed in order to expand the applicability domain and increase the confidence and reliability of data-driven nano-SARs. PMID:21456088

  13. APPLICATION OF FUSION WITH SAR AND OPTICAL IMAGES IN LAND USE CLASSIFICATION BASED ON SVM

    Directory of Open Access Journals (Sweden)

    C. Bao

    2012-07-01

    Full Text Available As the increment of remote sensing data with multi-space resolution, multi-spectral resolution and multi-source, data fusion technologies have been widely used in geological fields. Synthetic Aperture Radar (SAR and optical camera are two most common sensors presently. The multi-spectral optical images express spectral features of ground objects, while SAR images express backscatter information. Accuracy of the image classification could be effectively improved fusing the two kinds of images. In this paper, Terra SAR-X images and ALOS multi-spectral images were fused for land use classification. After preprocess such as geometric rectification, radiometric rectification noise suppression and so on, the two kind images were fused, and then SVM model identification method was used for land use classification. Two different fusion methods were used, one is joining SAR image into multi-spectral images as one band, and the other is direct fusing the two kind images. The former one can raise the resolution and reserve the texture information, and the latter can reserve spectral feature information and improve capability of identifying different features. The experiment results showed that accuracy of classification using fused images is better than only using multi-spectral images. Accuracy of classification about roads, habitation and water bodies was significantly improved. Compared to traditional classification method, the method of this paper for fused images with SVM classifier could achieve better results in identifying complicated land use classes, especially for small pieces ground features.

  14. Combining pharmacophore fingerprints and PLS-discriminant analysis for virtual screening and SAR elucidation

    DEFF Research Database (Denmark)

    Askjær, Sune; Langgård, Morten

    2008-01-01

    The criterion of success for the initial stages of a ligand-based drug-discovery project is dual. First, a set of suitable lead compounds has to be identified. Second, a level of a preliminary structure-activity relationship (SAR) of the identified ligands has to be established in order to guide ...... by the protein-binding site known from X-ray complexes. The result of this analysis assists in explaining the efficiency of 2D pharmacophore fingerprints as descriptors in virtual screening.......The criterion of success for the initial stages of a ligand-based drug-discovery project is dual. First, a set of suitable lead compounds has to be identified. Second, a level of a preliminary structure-activity relationship (SAR) of the identified ligands has to be established in order to guide...

  15. Discovery of unsymmetrical aromatic disulfides as novel inhibitors of SARS-CoV main protease: Chemical synthesis, biological evaluation, molecular docking and 3D-QSAR study.

    Science.gov (United States)

    Wang, Li; Bao, Bo-Bo; Song, Guo-Qing; Chen, Cheng; Zhang, Xu-Meng; Lu, Wei; Wang, Zefang; Cai, Yan; Li, Shuang; Fu, Sheng; Song, Fu-Hang; Yang, Haitao; Wang, Jian-Guo

    2017-09-08

    The worldwide outbreak of severe acute respiratory syndrome (SARS) in 2003 had caused a high rate of mortality. Main protease (Mpro) of SARS-associated coronavirus (SARS-CoV) is an important target to discover pharmaceutical compounds for the therapy of this life-threatening disease. During the course of screening new anti-SARS agents, we have identified that a series of unsymmetrical aromatic disulfides inhibited SARS-CoV Mpro significantly for the first time. Herein, 40 novel unsymmetrical aromatic disulfides were synthesized chemically and their biological activities were evaluated in vitro against SARS-CoV Mpro. These novel compounds displayed excellent IC50 data in the range of 0.516-5.954 μM. Preliminary studies indicated that these disulfides are reversible and mpetitive inhibitors. A possible binding mode was generated via molecular docking simulation and a comparative field analysis (CoMFA) model was constructed to understand the structure-activity relationships. The present research therefore has provided some meaningful guidance to design and identify anti-SARS drugs with totally new chemical structures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Expression, purification and crystallization of the SARS-CoV macro domain

    Energy Technology Data Exchange (ETDEWEB)

    Malet, Hélène; Dalle, Karen; Brémond, Nicolas; Tocque, Fabienne; Blangy, Stéphanie; Campanacci, Valérie; Coutard, Bruno; Grisel, Sacha; Lichière, Julie; Lantez, Violaine; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre, E-mail: marie-pierre.egloff@afmb.univ-mrs.fr [Centre National de la Recherche Scientifique and Universités d’Aix-Marseille I et II, UMR 6098, Architecture et Fonction des Macromolécules Biologiques, UMR 6098-Case 932, 163 Avenue de Luminy, 13288 Marseille CEDEX 9 (France)

    2006-04-01

    The SARS-CoV macro domain was expressed, purified and crystallized. Selenomethionine-labelled crystals diffracted to 1.8 Å resolution. Macro domains or X domains are found as modules of multidomain proteins, but can also constitute a protein on their own. Recently, biochemical and structural studies of cellular macro domains have been performed, showing that they are active as ADP-ribose-1′′-phosphatases. Macro domains are also present in a number of positive-stranded RNA viruses, but their precise function in viral replication is still unknown. The major human pathogen severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 16 non-structural proteins (nsps), one of which (nsp3) encompasses a macro domain. The SARS-CoV nsp3 gene region corresponding to amino acids 182–355 has been cloned, expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P2{sub 1}, with unit-cell parameters a = 37.5, b = 55.6, c = 108.9 Å, β = 91.4°, and the asymmetric unit contains either two or three molecules. Both native and selenomethionine-labelled crystals diffract to 1.8 Å.

  17. Relations of SARS-related stressors and coping to Chinese college students' psychological adjustment during the 2003 Beijing SARS epidemic.

    Science.gov (United States)

    Main, Alexandra; Zhou, Qing; Ma, Yue; Luecken, Linda J; Liu, Xin

    2011-07-01

    This study examined the main and interactive relations of stressors and coping related to severe acute respiratory syndrome (SARS) with Chinese college students' psychological adjustment (psychological symptoms, perceived general health, and life satisfaction) during the 2003 Beijing SARS epidemic. All the constructs were assessed by self-report in an anonymous survey during the final period of the outbreak. Results showed that the relations of stressors and coping to psychological adjustment varied by domain of adjustment. Regression analyses suggested that the number of stressors and use of avoidant coping strategies positively predicted psychological symptoms. Active coping positively predicted life satisfaction when controlling for stressors. Moreover, all types of coping served as a buffer against the negative impact of stressors on perceived general health. These findings hold implications for university counseling services during times of acute, large-scale stressors. In particular, effective screening procedures should be developed to identify students who experience a large number of stressors and thus are at high risk for developing mental health problems. Intervention efforts that target coping should be adapted to take account of the uncontrollability of stressors and clients' cultural preferences for certain coping strategies. A multidimensional battery of psychological adjustment should be used to monitor clients' psychological adjustment to stressors and evaluate the efficacy of intervention.

  18. Increased Levels of Plasma Epstein Barr Virus DNA Identify a Poor-Risk Subset of Patients With Advanced Stage Cutaneous T-Cell Lymphoma

    Science.gov (United States)

    Haverkos, Bradley M.; Gru, Alejandro A.; Geyer, Susan M.; Bingman, Anissa K.; Hemminger, Jessica A.; Mishra, Anjali; Wong, Henry K.; Pancholi, Preeti; Freud, Aharon G.; Caligiuri, Michael A.; Baiocchi, Robert A.; Porcu, Pierluigi

    2016-01-01

    Discovering prognostic factors that simultaneously describe tumor characteristics and improve risk stratification is a priority in cutaneous T-cell lymphoma (CTCL). More than a third of advanced stage CTCL patients in this cohort had detectable cell free plasma Epstein–Barr virus (EBV)-DNA (pEBVd) using quantitative real-time polymerase chain reaction. An increased level of pEBVd was highly concordant with EBV (ie, Epstein–Barr virus RNAs) in tumor tissue and was associated with inferior survival. Introduction Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein–Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. Patients and Methods Patients (n = 46; 2006–2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed. Results Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd+) than pEBVd− patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd+ and 22 of 29 pEBVd− patients; 12 of 14 (85.7%) pEBVd+ patients were EBER+ versus 0 of 22 pEBVd− patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd+ patients, but was not significant (10 of 14 pEBVd+ vs. 10 of 23 pEBVd−; P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd+ vs. 27 of 29 pEBVd−). pEBVd detection was associated with

  19. Federated query services provided by the Seamless SAR Archive project

    Science.gov (United States)

    Baker, S.; Bryson, G.; Buechler, B.; Meertens, C. M.; Crosby, C. J.; Fielding, E. J.; Nicoll, J.; Youn, C.; Baru, C.

    2013-12-01

    The NASA Advancing Collaborative Connections for Earth System Science (ACCESS) seamless synthetic aperture radar (SAR) archive (SSARA) project is a 2-year collaboration between UNAVCO, the Alaska Satellite Facility (ASF), the Jet Propulsion Laboratory (JPL), and OpenTopography at the San Diego Supercomputer Center (SDSC) to design and implement a seamless distributed access system for SAR data and derived data products (i.e. interferograms). A major milestone for the first year of the SSARA project was a unified application programming interface (API) for SAR data search and results at ASF and UNAVCO (WInSAR and EarthScope data archives) through the use of simple web services. A federated query service was developed using the unified APIs, providing users a single search interface for both archives (http://www.unavco.org/ws/brokered/ssara/sar/search). A command line client that utilizes this new service is provided as an open source utility for the community on GitHub (https://github.com/bakerunavco/SSARA). Further API development and enhancements added more InSAR specific keywords and quality control parameters (Doppler centroid, faraday rotation, InSAR stack size, and perpendicular baselines). To facilitate InSAR processing, the federated query service incorporated URLs for DEM (from OpenTopography) and tropospheric corrections (from the JPL OSCAR service) in addition to the URLs for SAR data. This federated query service will provide relevant QC metadata for selecting pairs of SAR data for InSAR processing and all the URLs necessary for interferogram generation. Interest from the international community has prompted an effort to incorporate other SAR data archives (the ESA Virtual Archive 4 and the DLR TerraSAR-X_SSC Geohazard Supersites and Natural Laboratories collections) into the federated query service which provide data for researchers outside the US and North America.

  20. Ebola Virus and Marburg Virus

    Science.gov (United States)

    Ebola virus and Marburg virus Overview Ebola virus and Marburg virus are related viruses that cause hemorrhagic fevers — illnesses marked by severe bleeding (hemorrhage), organ failure and, in many ...

  1. The flight test of Pi-SAR(L) for the repeat-pass interferometric SAR

    Science.gov (United States)

    Nohmi, Hitoshi; Shimada, Masanobu; Miyawaki, Masanori

    2006-09-01

    This paper describes the experiment of the repeat pass interferometric SAR using Pi-SAR(L). The air-borne repeat-pass interferometric SAR is expected as an effective method to detect landslide or predict a volcano eruption. To obtain a high-quality interferometric image, it is necessary to make two flights on the same flight pass. In addition, since the antenna of the Pi-SAR(L) is secured to the aircraft, it is necessary to fly at the same drift angle to keep the observation direction same. We built a flight control system using an auto pilot which has been installed in the airplane. This navigation system measures position and altitude precisely with using a differential GPS, and the PC Navigator outputs a difference from the desired course to the auto pilot. Since the air density is thinner and the speed is higher than the landing situation, the gain of the control system is required to be adjusted during the repeat pass flight. The observation direction could be controlled to some extent by adjusting a drift angle with using a flight speed control. The repeat-pass flight was conducted in Japan for three days in late November. The flight was stable and the deviation was within a few meters for both horizontal and vertical direction even in the gusty condition. The SAR data were processed in time domain based on range Doppler algorism to make the complete motion compensation. Thus, the interferometric image processed after precise phase compensation is shown.

  2. PolInSAR tomography for vertical profile retrieval of forest vegetation using spaceborne SAR data

    Science.gov (United States)

    Joshi, Sushil K.; Kumar, Shashi; Agrawal, Shefali; Dinh, Ho T. M.

    2016-05-01

    Forest height plays a crucial role to investigate the bio-physical parameters of forest and the terrestrial carbon. PolInSAR based inversion modeling has been successfully implemented on airborne and space-borne SAR data. SAR tomography, which is an extension of cross-track interferometric processing is a recent approach to separate scatterers in cross range direction, thus generates its vertical profile. This study highlighted the potential of tomographic processing of fully polarimetric Radarsat-2 SAR system to retrieve backscatter power at different height levels. Teak forest in Haldwani forest division of Uttarakhand state of India was chosen as the test site. Since SAR tomography is a spectral estimation problem, Fourier transform and beamforming based spectral estimations were applied on the dataset to obtain their vertical profiles. Fourier severely suffered from high side lobes which was drastically reduced by implementing beam-forming by taking into account the multi-looking effect at the expense of radiometric accuracy. Backscattered power values were found to be different at different height levels of the forest vegetation. Vertical profile for Fourier as well as beam-forming were also retrieved.

  3. SARS: Safeguards Accounting and Reporting Software

    Science.gov (United States)

    Mohammedi, B.; Saadi, S.; Ait-Mohamed, S.

    In order to satisfy the requirements of the SSAC (State System for Accounting and Control of nuclear materials), for recording and reporting objectives; this computer program comes to bridge the gape between nuclear facilities operators and national inspection verifying records and delivering reports. The SARS maintains and generates at-facility safeguards accounting records and generates International Atomic Energy Agency (IAEA) safeguards reports based on accounting data input by the user at any nuclear facility. A database structure is built and BORLAND DELPHI programming language has been used. The software is designed to be user-friendly, to make extensive and flexible management of menus and graphs. SARS functions include basic physical inventory tacking, transaction histories and reporting. Access controls are made by different passwords.

  4. Estimating the Doppler centroid of SAR data

    DEFF Research Database (Denmark)

    Madsen, Søren Nørvang

    1989-01-01

    After reviewing frequency-domain techniques for estimating the Doppler centroid of synthetic-aperture radar (SAR) data, the author describes a time-domain method and highlights its advantages. In particular, a nonlinear time-domain algorithm called the sign-Doppler estimator (SDE) is shown to have...... attractive properties. An evaluation based on an existing SEASAT processor is reported. The time-domain algorithms are shown to be extremely efficient with respect to requirements on calculations and memory, and hence they are well suited to real-time systems where the Doppler estimation is based on raw SAR...... data. For offline processors where the Doppler estimation is performed on processed data, which removes the problem of partial coverage of bright targets, the ΔE estimator and the CDE (correlation Doppler estimator) algorithm give similar performance. However, for nonhomogeneous scenes it is found...

  5. SAR observations in the Gulf of Mexico

    Science.gov (United States)

    Sheres, David

    1992-01-01

    The Gulf of Mexico (GOM) exhibits a wealth of energetic ocean features; they include the Loop Current with velocities of about 2 m/s and strong shear fronts, mesoscale eddies, double vortices, internal waves, and the outflow of the 'Mighty Mississippi' river. These energetic features can have a strong impact on the economies of the states surrounding the Gulf. Large fisheries, oil and gas production as well as pollution transport are relevant issues. These circulation features in the Gulf are invisible to conventional IR and visible satellite imagery during the Summer months due to cloud cover and uniform surface temperatures. Synthetic Aperture Radar (SAR) imagery of the Gulf does penetrate the cloud cover and shows a rich assembly of features there year-round. Below are preliminary results from GOM SAR imagery taken by SEASAT in 1978 and by the AIRSAR program in 1991.

  6. Viruses and Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lawson, James S., E-mail: james.lawson@unsw.edu.au; Heng, Benjamin [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney (Australia)

    2010-04-30

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

  7. Clinical Trial Registries Are of Minimal Use for Identifying Selective Outcome and Analysis Reporting

    Science.gov (United States)

    Norris, Susan L.; Holmer, Haley K.; Fu, Rongwei; Ogden, Lauren A.; Viswanathan, Meera S.; Abou-Setta, Ahmed M.

    2014-01-01

    Objective: This study aimed to examine selective outcome reporting (SOR) and selective analysis reporting (SAR) in randomized controlled trials (RCTs) and to explore the usefulness of trial registries for identifying SOR and SAR. Study Design and Setting: We selected one "index outcome" for each of three comparative effectiveness reviews…

  8. SAR Product Improvements and Enhancements - SARprises

    Science.gov (United States)

    2013-09-30

    paper on current fields at Orkney, Scotland, was accepted for publication in IEEE - TGARS and is currently in press (available on IEEE Xplore as Early...Sea surface velocity vector retrieval using dual-beam interferometry: First demonstration, IEEE TGARS, 43, 2494- 2502, 2005. [2] Chapron, B., F...Bight by airborne along-track interferometric SAR, Proc. IGARSS 2002, 1822-1824, IEEE , 2002. [4] Bjerklie, D.M., S.L. Dingman, C.J. Vorosmarty, C.H

  9. SAR Polarimetric Scattering from Natural Terrains

    Science.gov (United States)

    2017-02-17

    calculate the polarimetric speckle statistics (amplitude and phase difference), followed by a comparison with theoretical distributions . For fully developed...AFRL-AFOSR-JP-TR-2017-0013 SAR Polarimetric Scattering from Natural Terrains Kun-Shan Chen National Central University Final Report 02/17/2017... DISTRIBUTION A: Distribution approved for public release. AF Office Of Scientific Research (AFOSR)/ IOA Arlington, Virginia 22203 Air Force Research

  10. Cross-calibration of interferometric SAR data

    DEFF Research Database (Denmark)

    Dall, Jørgen

    2003-01-01

    Generation of digital elevation models from interferometric synthetic aperture radar (SAR) data is a well established technique. Achieving a high geometric fidelity calls for a calibration accounting for inaccurate navigation data and system parameters as well as system imperfections. Fully...... automated calibration techniques are preferable, especially for operational mapping. The author presents one such technique, called cross-calibration. Though developed for single-pass interferometry, it may be applicable to multi-pass interferometry, too. Cross-calibration requires stability during mapping...

  11. Mutation of Asn28 Disrupts the Dimerization and Enzymatic Activity of SARS 3CL

    Energy Technology Data Exchange (ETDEWEB)

    Barrila, J.; Gabelli, S; Bacha, U; Amzel, M; Freire, E

    2010-01-01

    Coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. The most prominent of these viruses is the severe acute respiratory syndrome coronavirus (SARS-CoV) which causes acute respiratory and gastrointestinal infection in humans. The coronavirus main protease, 3CL{sup pro}, is a key target for broad-spectrum antiviral development because of its critical role in viral maturation and high degree of structural conservation among coronaviruses. Dimerization is an indispensable requirement for the function of SARS 3CL{sup pro} and is regulated through mechanisms involving both direct and long-range interactions in the enzyme. While many of the binding interactions at the dimerization interface have been extensively studied, those that are important for long-range control are not well-understood. Characterization of these dimerization mechanisms is important for the structure-based design of new treatments targeting coronavirus-based infections. Here we report that Asn28, a residue 11 {angstrom} from the closest residue in the opposing monomer, is essential for the enzymatic activity and dimerization of SARS 3CLpro. Mutation of this residue to alanine almost completely inactivates the enzyme and results in a 19.2-fold decrease in the dimerization K{sub d}. The crystallographic structure of the N28A mutant determined at 2.35 {angstrom} resolution reveals the critical role of Asn28 in maintaining the structural integrity of the active site and in orienting key residues involved in binding at the dimer interface and substrate catalysis. These findings provide deeper insight into complex mechanisms regulating the activity and dimerization of SARS 3CL{sup pro}.

  12. Feature-Based Nonlocal Polarimetric SAR Filtering

    Directory of Open Access Journals (Sweden)

    Xiaoli Xing

    2017-10-01

    Full Text Available Polarimetric synthetic aperture radar (PolSAR images are inherently contaminated by multiplicative speckle noise, which complicates the image interpretation and image analyses. To reduce the speckle effect, several adaptive speckle filters have been developed based on the weighted average of the similarity measures commonly depending on the model or probability distribution, which are often affected by the distribution parameters and modeling texture components. In this paper, a novel filtering method introduces the coefficient of variance ( CV and Pauli basis (PB to measure the similarity, and the two features are combined with the framework of the nonlocal mean filtering. The CV is used to describe the complexity of various scenes and distinguish the scene heterogeneity; moreover, the Pauli basis is able to express the polarimetric information in PolSAR image processing. This proposed filtering combines the CV and Pauli basis to improve the estimation accuracy of the similarity weights. Then, the similarity of the features is deduced according to the test statistic. Subsequently, the filtering is proceeded by using the nonlocal weighted estimation. The performance of the proposed filter is tested with the simulated images and real PolSAR images, which are acquired by AIRSAR system and ESAR system. The qualitative and quantitative experiments indicate the validity of the proposed method by comparing with the widely-used despeckling methods.

  13. Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola virus in Rhesus Monkeys

    Science.gov (United States)

    2016-03-02

    yellow fever virus, dengue virus type 2), parainfluenza type 3, and severe 124 acute respiratory syndrome (SARS) associated coronavirus but little or...Culture Collection. HEp-2 cells were cultured in Eagle’s Minimum Essential Media (MEM) 409 with GlutaMAX TM supplemented with 10% fetal bovine

  14. Human Infection with Avian Influenza A(H7N9) Virus - China

    Science.gov (United States)

    ... response operations Diseases Biorisk reduction Disease outbreak news Human infection with avian influenza A(H7N9) virus – ... Region (SAR) notified WHO of a laboratory-confirmed human infection with avian influenza A(H7N9) virus and ...

  15. A 3-D SAR approach to IFSAR processing

    Energy Technology Data Exchange (ETDEWEB)

    DOERRY,ARMIN W.; BICKEL,DOUGLAS L.

    2000-03-01

    Interferometric SAR (IFSAR) can be shown to be a special case of 3-D SAR image formation. In fact, traditional IFSAR processing results in the equivalent of merely a super-resolved, under-sampled, 3-D SAR image. However, when approached as a 3-D SAR problem, a number of IFSAR properties and anomalies are easily explained. For example, IFSAR decorrelation with height is merely ordinary migration in 3-D SAR. Consequently, treating IFSAR as a 3-D SAR problem allows insight and development of proper motion compensation techniques and image formation operations to facilitate optimal height estimation. Furthermore, multiple antenna phase centers and baselines are easily incorporated into this formulation, providing essentially a sparse array in the elevation dimension. This paper shows the Polar Format image formation algorithm extended to 3 dimensions, and then proceeds to apply it to the IFSAR collection geometry. This suggests a more optimal reordering of the traditional IFSAR processing steps.

  16. Low-SAR metamaterial-inspired printed monopole antenna

    Science.gov (United States)

    Hossain, M. I.; Faruque, M. R. I.; Islam, M. T.; Ali, M. T.

    2017-01-01

    In this paper, a low-SAR metamaterial-embedded planar monopole antenna is introduced for a wireless communication system. A printed monopole antenna is designed for modern mobile, which operates in GSM, UMTS, LTE, WLAN, and Bluetooth frequency bands. A metamaterial structure is designed to use in the mobile handset with a multi-band printed monopole antenna. The finite integration technique of the CST microwave studio is used in this study. The measurement of antenna performances is taken in an anechoic chamber, and the SAR values are measured using COMOSAR system. The results indicate that metamaterial structure leads to reduce SAR without affecting antenna performance significantly. According to the measured results, the metamaterial attachment leads to reduce 87.7% peak SAR, 68.2% 1-g SAR, and 46.78% 10-g SAR compared to antenna without metamaterial.

  17. Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes.

    Science.gov (United States)

    Lin, Min-Han; Moses, David C; Hsieh, Chih-Hua; Cheng, Shu-Chun; Chen, Yau-Hung; Sun, Chiao-Yin; Chou, Chi-Yuan

    2017-12-28

    Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in southern China in late 2002 and caused a global outbreak with a fatality rate around 10% in 2003. Ten years later, a second highly pathogenic human CoV, MERS-CoV, emerged in the Middle East and has spread to other countries in Europe, North Africa, North America and Asia. As of November 2017, MERS-CoV had infected at least 2102 people with a fatality rate of about 35% globally, and hence there is an urgent need to identify antiviral drugs that are active against MERS-CoV. Here we show that a clinically available alcohol-aversive drug, disulfiram, can inhibit the papain-like proteases (PLpros) of MERS-CoV and SARS-CoV. Our findings suggest that disulfiram acts as an allosteric inhibitor of MERS-CoV PLpro but as a competitive (or mixed) inhibitor of SARS-CoV PLpro. The phenomenon of slow-binding inhibition and the irrecoverability of enzyme activity after removing unbound disulfiram indicate covalent inactivation of SARS-CoV PLpro by disulfiram, while synergistic inhibition of MERS-CoV PLpro by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. VHL negatively regulates SARS coronavirus replication by modulating nsp16 ubiquitination and stability.

    Science.gov (United States)

    Yu, Xiao; Chen, Shuliang; Hou, Panpan; Wang, Min; Chen, Yu; Guo, Deyin

    2015-04-03

    Eukaryotic cellular and most viral RNAs carry a 5'-terminal cap structure, a 5'-5' triphosphate linkage between the 5' end of the RNA and a guanosine nucleotide (cap-0). SARS coronavirus (SARS-CoV) nonstructural protein nsp16 functions as a methyltransferase, to methylate mRNA cap-0 structure at the ribose 2'-O position of the first nucleotide to form cap-1 structures. However, whether there is interplay between nsp16 and host proteins was not yet clear. In this report, we identified several potential cellular nsp16-interacting proteins from a human thymus cDNA library by yeast two-hybrid screening. VHL, one of these proteins, was proven to interact with nsp16 both in vitro and in vivo. Further studies showed that VHL can inhibit SARS-CoV replication by regulating nsp16 ubiquitination and promoting its degradation. Our results have revealed the role of cellular VHL in the regulation of SARS-CoV replication. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Advanced Unsupervised Classification Methods to Detect Anomalies on Earthen Levees Using Polarimetric SAR Imagery

    Directory of Open Access Journals (Sweden)

    Ramakalavathi Marapareddy

    2016-06-01

    Full Text Available Fully polarimetric Synthetic Aperture Radar (polSAR data analysis has wide applications for terrain and ground cover classification. The dynamics of surface and subsurface water events can lead to slope instability resulting in slough slides on earthen levees. Early detection of these anomalies by a remote sensing approach could save time versus direct assessment. We used L-band Synthetic Aperture Radar (SAR to screen levees for anomalies. SAR technology, due to its high spatial resolution and soil penetration capability, is a good choice for identifying problematic areas on earthen levees. Using the parameters entropy (H, anisotropy (A, alpha (α, and eigenvalues (λ, λ1, λ2, and λ3, we implemented several unsupervised classification algorithms for the identification of anomalies on the levee. The classification techniques applied are H/α, H/A, A/α, Wishart H/α, Wishart H/A/α, and H/α/λ classification algorithms. In this work, the effectiveness of the algorithms was demonstrated using quad-polarimetric L-band SAR imagery from the NASA Jet Propulsion Laboratory’s (JPL’s Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR. The study area is a section of the lower Mississippi River valley in the Southern USA, where earthen flood control levees are maintained by the US Army Corps of Engineers.

  20. Advanced Unsupervised Classification Methods to Detect Anomalies on Earthen Levees Using Polarimetric SAR Imagery.

    Science.gov (United States)

    Marapareddy, Ramakalavathi; Aanstoos, James V; Younan, Nicolas H

    2016-06-16

    Fully polarimetric Synthetic Aperture Radar (polSAR) data analysis has wide applications for terrain and ground cover classification. The dynamics of surface and subsurface water events can lead to slope instability resulting in slough slides on earthen levees. Early detection of these anomalies by a remote sensing approach could save time versus direct assessment. We used L-band Synthetic Aperture Radar (SAR) to screen levees for anomalies. SAR technology,