Flaviviridae

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Graham J. Belsham - One of the best experts on this subject based on the ideXlab platform.

  • structural features of the seneca valley virus internal ribosome entry site ires element a picornavirus with a pestivirus like ires
    Journal of Virology, 2011
    Co-Authors: Margaret M Willcocks, Graham J. Belsham, Nicolas Locker, Zarmwa Gomwalk, Elizabeth Royall, Mehran Bakhshesh, Neeraja Idamakanti, Kevin D Burroughs, Seshidhar P Reddy, Paul L Hallenbeck
    Abstract:

    The RNA genome of Seneca Valley virus (SVV), a recently identified picornavirus, contains an internal ribosome entry site (IRES) element which has structural and functional similarity to that from classical swine fever virus (CSFV) and hepatitis C virus, members of the Flaviviridae. The SVV IRES has an absolute requirement for the presence of a short region of virus-coding sequence to allow it to function either in cells or in rabbit reticulocyte lysate. The IRES activity does not require the translation initiation factor eIF4A or intact eIF4G. The predicted secondary structure indicates that the SVV IRES is more closely related to the CSFV IRES, including the presence of a bipartite IIId domain. Mutagenesis of the SVV IRES, coupled to functional assays, support the core elements of the IRES structure model, but surprisingly, deletion of the conserved IIId(2) domain had no effect on IRES activity, including 40S and eIF3 binding. This is the first example of a picornavirus IRES that is most closely related to the CSFV IRES and suggests the possibility of multiple, independent recombination events between the genomes of the Picornaviridae and Flaviviridae to give rise to similar IRES elements.

  • Hepatitis C virus-related internal ribosome entry sites are found in multiple genera of the family Picornaviridae.
    Journal of General Virology, 2006
    Co-Authors: Louisa S. Chard, Marie-eve Bordeleau, Jerry Pelletier, Junichi Tanaka, Graham J. Belsham
    Abstract:

    The internal ribosome entry site (IRES) elements from porcine enterovirus 8 and simian virus 2, two members of a proposed new genus within the family Picornaviridae, were characterized. These IRES elements, in common with the porcine teschovirus 1 IRES, were found to be related functionally and structurally to the IRES element from Hepatitis C virus, a member of the family Flaviviridae. Partial secondary structure predictions were derived and functional assays demonstrated that these IRES elements continued to be active when eIF4G was cleaved and when the activity of eIF4A was blocked.

J D Russell - One of the best experts on this subject based on the ideXlab platform.

Peter Simmonds - One of the best experts on this subject based on the ideXlab platform.

  • Proposed revision to the taxonomy of the genus Pestivirus, family Flaviviridae.
    The Journal of general virology, 2017
    Co-Authors: D B Smith, Gregor Meyers, Jens Bukh, Ernest A. Gould, Thomas P. Monath, A. Scott Muerhoff, Alexander G. Pletnev, Rebecca Rico-hesse, Jack T. Stapleton, Peter Simmonds
    Abstract:

    We propose the creation of seven new species in the genus Pestivirus (family Flaviviridae) in addition to the four existing species, and naming species in a host-independent manner using the format Pestivirus X. Only the virus species names would change; virus isolates would still be referred to by their original names. The original species would be re-designated as Pestivirus A (original designation B ovine viral diarrhea virus 1), Pestivirus B (Bovine viral diarrhea virus 2), Pestivirus C (Classical swine fever virus) and Pestivirus D (Border disease virus). The seven new species (and example isolates) would be Pestivirus E (pronghorn pestivirus), Pestivirus F (Bungowannah virus), Pestivirus G (giraffe pestivirus), Pestivirus H (Hobi-like pestivirus), Pestivirus I (Aydin-like pestivirus), Pestivirus J (rat pestivirus) and Pestivirus K (atypical porcine pestivirus). A bat-derived virus and pestiviruses identified from sheep and goat (Tunisian sheep pestiviruses), which lack complete coding region sequences, may represent two additional species.

  • The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae
    Journal of General Virology, 2010
    Co-Authors: Steven K. H. Foung, Jens Bukh, A. Scott Muerhoff, Peter Simmonds
    Abstract:

    In 1967, it was reported that experimental inoculation of serum from a surgeon (G.B.) with acute hepatitis into tamarins resulted in hepatitis. In 1995, two new members of the family Flaviviridae, named GBV-A and GBV-B, were identified in tamarins that developed hepatitis following inoculation with the 11th GB passage. Neither virus infects humans, and a number of GBV-A variants were identified in wild New World monkeys that were captured. Subsequently, a related human virus was identified [named GBV-C or hepatitis G virus (HGV)], and recently a more distantly related virus (named GBV-D) was discovered in bats. Only GBV-B, a second species within the genus Hepacivirus (type species hepatitis C virus), has been shown to cause hepatitis; it causes acute hepatitis in experimentally infected tamarins. The other GB viruses have however not been assigned to a genus within the family Flaviviridae. Based on phylogenetic relationships, genome organization and pathogenic features of the GB viruses, we propose to classify GBV-A-like viruses, GBV-C and GBV-D as members of a fourth genus in the family Flaviviridae, named Pegivirus (pe, persistent; g, GB or G). We also propose renaming ‘GB’ viruses within the tentative genus Pegivirus to reflect their host origin.

Charles M. Rice - One of the best experts on this subject based on the ideXlab platform.

  • Identification and Characterization of the Host Protein DNAJC14 as a Broadly Active Flavivirus Replication Modulator
    2016
    Co-Authors: Lindsey Sperzel, Peter J. Bredenbeek, Kirk J. Lubick, Sonja M, Cristina T. Stoyanov, Lok Man, J. Law, Zhenghong Yuan, Charles M. Rice
    Abstract:

    Viruses in the Flavivirus genus of the Flaviviridae family are arthropod-transmitted and contribute to staggering numbers of human infections and significant deaths annually across the globe. To identify cellular factors with antiviral activity against flaviviruses, we screened a cDNA library using an iterative approach. We identified a mammalian Hsp40 chaperone protein (DNAJC14) that when overexpressed was able to mediate protection from yellow fever virus (YFV)-induced cell death. Further studies revealed that DNAJC14 inhibits YFV at the step of viral RNA replication. Since replication of bovine viral diarrhea virus (BVDV), a member of the related Pestivirus genus, is also known to be modulated by DNAJC14, we tested the effect of this host factor on diverse Flaviviridae family members. Flaviviruses, including the pathogenic Asibi strain of YFV, Kunjin, and tick-borne Langat virus, as well as a Hepacivirus, hepatitis C virus (HCV), all were inhibited by overexpression of DNAJC14. Mutagenesis showed that both the J-domain and the C-terminal domain, which mediates self-interaction, are required for anti-YFV activity. We found that DNAJC14 does not block YFV nor HCV NS2-3 cleavage, and using non-inhibitory mutants demonstrate that DNAJC14 is recruited to YFV replication complexes. Immunofluorescence analysis demonstrated that endogenous DNAJC14 rearranges during infection and is found in replication complexes identified by dsRNA staining. Interestingly, silencing of endogenous DNAJC14 results in impaired YFV replication suggesting

  • Architects of assembly: roles of Flaviviridae non-structural proteins in virion morphogenesis
    Nature reviews. Microbiology, 2008
    Co-Authors: Catherine L. Murray, Christopher T. Jones, Charles M. Rice
    Abstract:

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

  • Flaviviridae t he viruses and their replication
    2007
    Co-Authors: Brett Lindenbach D Heinzj, Charles M. Rice
    Abstract:

    FLAVIVIRUSES 1103 Background and Classification 1103 Structure and Physical Properties of the Virion 1104 Binding and Entry 1105 Genome Structure 1106 Translation and Proteolytic Processing 1107 Features of the Structural Proteins 1108 Features of the Nonstructural Proteins 1109 RNA Replication 1112 Membrane Reorganization and the Compartmentalization of Flavivirus Replication 1112 Assembly and Release of Particles from Flavivirus-infected Cells 1112 Host Resistance to Flavivirus Infection 1113

  • hepatitis c virus ns3 protein polynucleotide stimulated nucleoside triphosphatase and comparison with the related pestivirus and flavivirus enzymes
    Journal of Virology, 1993
    Co-Authors: Joann Suzich, Charles M. Rice, J K Tamura, F Palmerhill, P Warrener, Arash Grakoui, Stephen M Feinstone, Marc S Collett
    Abstract:

    Sequence motifs within the nonstructural protein NS3 of members of the Flaviviridae family suggest that this protein possesses nucleoside triphosphatase (NTPase) and RNA helicase activity. The RNA-stimulated NTPase activity of this protein from prototypic members of the Pestivirus and Flavivirus genera has recently been established and enzymologically characterized. Here, we experimentally demonstrate that the NS3 protein from a member of the third genus of Flaviviridae, human hepatitis C virus (HCV), also possesses a polynucleotide-stimulated NTPase activity. Characterization of the purified HCV NTPase activity showed that it exhibited reaction condition optima with respect to pH, MgCl2, and salt identical to those of the representative pestivirus and flavivirus enzymes. However, each NTPase also possessed several unique properties when compared with one another. Notably, the profile of polynucleotide stimulation of the NTPase activity was distinct for the three enzymes. The HCV NTPase was the only one whose activity was significantly enhanced by a deoxyribopolynucleotide. Additional distinguishing features among the three enzymes relating to the kinetic properties of their NTPase activities are discussed. These studies provide a foundation for investigation of the putative RNA helicase activity of these proteins and for further study of the role of the NS3 proteins of members of the Flaviviridae in the replication cycle of these viruses.

M I Voevoda - One of the best experts on this subject based on the ideXlab platform.

  • single nucleotide polymorphism in the promoter region of the cd209 gene is associated with human predisposition to severe forms of tick borne encephalitis
    Antiviral Research, 2012
    Co-Authors: Andrey V Barkhash, Andrey A Perelygin, Vladimir N Babenko, Margo A Brinton, M I Voevoda
    Abstract:

    Abstract Tick-borne encephalitis virus (TBEV) is a neurotropic, positive-sense RNA virus of the genus Flavivirus (family Flaviviridae ) which can cause a variety of clinical manifestations in humans. Previously the severity and outcome of dengue fever and hepatitis C (diseases caused by viruses from the family Flaviviridae ) were associated with the rs4804803 single nucleotide polymorphism (SNP) located in the promoter region of the human CD209 gene. This gene encodes dendritic cell-specific ICAM3-grabbing nonintegrin (DC-SIGN), a C-type lectin pathogen-recognition receptor expressed on the surface of dendritic cells and some types of macrophages. In the current study, a possible association between two SNPs in the promoter region of the CD209 gene (rs4804803 and rs2287886) and predisposition to severe forms of TBEV-induced disease was investigated. The genotypic, allelic and haplotypic frequencies of these SNPs were analyzed in 136 non-immunized Russian patients with different clinical manifestations of tick-borne encephalitis (TBE) and in a control group. An increase in the frequency of the rs2287886 SNP AA homozygotes and the A allele was detected among patients with severe central nervous system disease compared with the group of patients with meningitis ( P  = 0.003 and 0.019), or a combined group of patients with mild forms (fever and meningitis) ( P  = 0.003 and 0.026), or the control group ( P  = 0.007 and 0.035). Thus, our results suggest that the CD209 gene promoter region rs2287886 SNP is associated with predisposition to severe forms of TBE in the Russian population.