The Experts below are selected from a list of 216 Experts worldwide ranked by ideXlab platform
Gary W Blissard - One of the best experts on this subject based on the ideXlab platform.
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The Pre-Transmembrane Domain of the Autographa californica Multicapsid Nucleopolyhedrovirus GP64 Protein Is Critical for Membrane Fusion and Virus Infectivity
Journal of virology, 2009Co-Authors: Gary W BlissardAbstract:The envelope glycoprotein, GP64, of the baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) is a class III viral fusion protein that mediates pH-triggered membrane fusion during virus entry. Viral fusion glycoproteins from many viruses contain a short region in the ectodomain and near the transmembrane domain, referred to as the pre-transmembrane (PTM) domain. In some cases, the PTM domain is rich in aromatic amino acids and plays an important role in membrane fusion. Although the 23-amino-acid (aa) PTM domain of AcMNPV GP64 lacks aromatic amino acids, we asked whether this region might also play a significant role in membrane fusion. We generated alanine scanning and single and multiple amino acid substitutions in the GP64 PTM domain. We specifically focused on amino acid positions conserved between baculovirus GP64 and Thogotovirus GP75 proteins, as well as hydrophobic and charged amino acids. For each PTM-modified construct, we examined trimerization, cell surface localization, and membrane fusion activity. Membrane merger and pore formation were also examined. We identified eight aa positions that are important for membrane fusion activity. Critical positions were not clustered in the linear sequence but were distributed throughout the PTM domain. While charged residues were not critical or essential, three hydrophobic amino acids (L465, L476, and L480) played an important role in membrane fusion activity and appear to be involved in formation of the fusion pore. We also asked whether selected GP64 constructs were capable of rescuing a gp64null AcMNPV virus. These studies suggested that several conserved residues (T463, G460, G462, and G474) were not required for membrane fusion but were important for budding and viral infectivity.
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Functional Analysis of the Transmembrane (TM) Domain of the Autographa californica Multicapsid Nucleopolyhedrovirus GP64 Protein: Substitution of Heterologous TM Domains
Journal of virology, 2008Co-Authors: Gary W BlissardAbstract:GP64, the major envelope glycoprotein of the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) budded virion, is important for host cell receptor binding and mediates low-pH-triggered membrane fusion during entry by endocytosis. In the current study, we examined the functional role of the AcMNPV GP64 transmembrane (TM) domain by replacing the 23-amino-acid GP64 TM domain with corresponding TM domain sequences from a range of viral and cellular type I membrane proteins, including Orgyia pseudotsugata MNPV (OpMNPV) GP64 and F, Thogotovirus GP75, Lymantria dispar MNPV (LdMNPV) F, human immunodeficiency virus type 1 (HIV-1) GP41, human CD4 and glycophorin A (GpA), and influenza virus hemagglutinin (HA), and with a glycosylphosphatidylinositol (GPI) anchor addition sequence. In transient expression experiments with Sf9 cells, chimeric GP64 proteins containing either a GPI anchor or TM domains from LdMNPV F or HIV-1 GP41 failed to localize to the cell surface and thus appear to be incompatible with either GP64 structure or cell transport. All of the mutant constructs detected at the cell surface mediated hemifusion (outer leaflet merger) upon low-pH treatment, but only those containing TM domains from CD4, GpA, OpMNPV GP64, and Thogotovirus GP75 mediated pore formation and complete membrane fusion activity. This supports a model in which partial fusion (hemifusion) proceeds by a mechanism that is independent of the TM domain and the TM domain participates in the enlargement or expansion of fusion pores after hemifusion. GP64 proteins containing heterologous TM domains mediated virion budding with dramatically differing levels of efficiency. In addition, chimeric GP64 proteins containing TM domains from CD4, GpA, HA, and OpMNPV F were incorporated into budded virions but were unable to rescue the infectivity of a gp64 null virus, whereas those with TM domains from OpMNPV GP64 and Thogotovirus GP75 rescued infectivity. These results show that in addition to its basic role in membrane anchoring, the GP64 TM domain is critically important for GP64 trafficking, membrane fusion, virion budding, and virus infectivity. These critical functions were replaced only by TM domains from related viral membrane proteins.
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1. Persistent Gene Expression in Mouse Nasal Epithelia Following Baculovirus GP64 Pseudotyped FIV-Based Gene Transfer
Molecular Therapy, 2005Co-Authors: Patrick L. Sinn, Erin R. Burnight, Melissa A Hickey, Gary W Blissard, Paul B. MccrayAbstract:The use of gene transfer to treat or prevent cystic fibrosis lung disease has been limited in part by the inability of vectors to efficiently and persistently transduce airway epithelia. Influenza A is an enveloped virus with natural lung tropism; however, pseudotyping feline immunodeficiency virus (FIV)-based lentiviral vector with the HA and HEF envelope proteins proved unsuccessful. Conversely, influenza D has a single envelope protein (GP64) and pseudotyping FIV with influenza D GP64 (from Thogotovirus) resulted in titers of 10e6 TU/ml. Further, influenza D GP64 conferred FIV apical entry into well-differentiated human airway epithelial cells. Baculovirus GP64 envelope glycoproteins share sequence identity with influenza D envelope glycoproteins, the result of a postulated lateral transfer of genetic material during the evolution of the two viral families. Pseudotyping FIV with GP64 from 3 species of baculovirus resulted in titers ranging from 10e7|[ndash]|10e9 TU/ml. Of note, GP64 from Autographa californica multinuclear polyhedrosis virus resulted in high titer FIV preparations (upwards of 10e9 TU/ml) and also conferred apical entry into polarized primary cultures of human airway epithelia. These titers equal those obtained with VSV-G pseudotyping. Using a luciferase reporter gene and bioluminescent imaging, we observed persistent in vivo gene transfer in the mouse nose with A. californica GP64 pseudotyped FIV (AcGP64-FIV). Longitudinal bioluminescence analysis has documented the persistence of expression in the nasal epithelia for >7 months without significant decline. We used a nuclear targeted beta-galactosidase reporter and histologicial analysis to demonstrate that surface epithelial cells were transduced in the mouse sinuses. In addition, AcGP64-FIV transduced mouse nasal epithelia with much greater efficiency than VSV-G pseudotyped FIV, as determined by both bioluminescence and histological analysis. These data suggest that AcGP64-FIV efficiently and persistently transduces nasal epithelia in the absence of agents that disrupt the cellular tight junction integrity and have important implications for CF gene therapy.
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688 pseudotyping fiv based lentiviral vectors with baculovirus gp64 confers apical entry into airway epithelia
Molecular Therapy, 2004Co-Authors: Patrick L. Sinn, Erin R. Burnight, Douglas E Dylla, Christina S Firm, Melissa A Hickey, Gary W Blissard, Paul B. MccrayAbstract:Top of pageAbstract The use of gene transfer to treat or prevent cystic fibrosis lung disease has been limited in part by the inability of vectors to efficiently transduce airway epithelia from the apical surface. Using a feline immunodeficiency virus (FIV)-based lentiviral vector system, we recently observed that the envelope glycoprotein GP64 from baculovirus Autographa californica nucleopolyhedrovirus (AcMNPV) confers apical entry into polarized primary cultures of human airway epithelia. High titer FIV-vector (>10e9 TU/ml) was achieved by pseudotyping with baculovirus GP64 (GP64-FIV) and these titers meet or exceed those obtained with the VSV-G envelope. We tested fusion (F) proteins from four other baculoviruses for their ability to pseudotype FIV, and obtained very low titers (less than or equal to 10e2). Interestingly, AcMNPV GP64 shares sequence identity with influenza D envelope GPs such as Thogotovirus. Pseudotyping FIV with Thogoto GP resulted in titers of ~10e6 TU/ml and also conferred apical entry into polarized human airway epithelial cell cultures. These data lend support to the notion of horizontal transfer of GPs during the evolution of AcMNPV and Influenza D viruses. The receptor for GP64 is currently unknown; however, we investigated the entry of GP64-FIV into epithelia. Pretreating A549 cells with the ionophores monensin or NH4Cl significantly decreased the transduction by GP64-FIV as measured by beta-Galactosidase expression. These data suggest that similar to VSV-G, GP64-FIV transduction requires a low pH endosome pathway. These findings identify a pseudotyped, integrating viral vector with the capacity to infect from the apical surface for the convenient delivery of transgenes to airway epithelia.
Robert B. Tesh - One of the best experts on this subject based on the ideXlab platform.
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Upolu Virus and Aransas Bay Virus, Two Presumptive Bunyaviruses, Are Novel Members of the Family Orthomyxoviridae
2016Co-Authors: Robert B. Tesh, B Ian W. LipkinaAbstract:Emerging and zoonotic pathogens pose continuing threats to human health and ongoing challenges to diagnostics. As nucleic acid tests are playing increasingly prominent roles in diagnostics, the genetic characterization of molecularly uncharacterized agents is expected to significantly enhance detection and surveillance capabilities. We report the identification of two previously unrecognized members of the familyOrthomyxoviridae, which includes the influenza viruses and the tick-transmitted Thogoto and Dhori viruses. We provide morphological, serologic, and genetic evidence thatUpolu virus (UPOV) from Australia and Aransas Bay virus (ABV) from North America, both previously considered potential bunyaviruses based on electron microscopy and physicochemical features, are orthomyxoviruses instead. Their genomes show up to 68 % nucleotide sequence identity to Thogoto virus (segment 2;74 % at the amino acid level) and a more distant relationship to Dhori virus, the two prototype vi-ruses of the recognized species of the genus Thogotovirus. Despite sequence similarity, the coding potentials of UPOV and ABV differed from that of Thogoto virus, instead being like that of Dhori virus. Our findings suggest that the tick-transmitted viruses UPOV and ABV represent geographically distinct viruses in the genus Thogotovirus of the familyOrthomyxoviridae that do not fit in the two currently recognized species of this genus. IMPORTANCE Upolu virus (UPOV) andAransas Bay virus (ABV) are shown to be orthomyxoviruses instead of bunyaviruses, as previously thought
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Upolu virus and Aransas Bay virus, Two Presumptive Bunyaviruses, Are Novel Members of the Family Orthomyxoviridae
Journal of Virology, 2014Co-Authors: Thomas Briese, Amelia P. A. Travassos Da Rosa, Robert B. Tesh, Vsevolod L. Popov, Rashmi Chowdhary, Stephen K. Hutchison, Craig Street, W. Ian LipkinAbstract:UNLABELLED Emerging and zoonotic pathogens pose continuing threats to human health and ongoing challenges to diagnostics. As nucleic acid tests are playing increasingly prominent roles in diagnostics, the genetic characterization of molecularly uncharacterized agents is expected to significantly enhance detection and surveillance capabilities. We report the identification of two previously unrecognized members of the family Orthomyxoviridae, which includes the influenza viruses and the tick-transmitted Thogoto and Dhori viruses. We provide morphological, serologic, and genetic evidence that Upolu virus (UPOV) from Australia and Aransas Bay virus (ABV) from North America, both previously considered potential bunyaviruses based on electron microscopy and physicochemical features, are orthomyxoviruses instead. Their genomes show up to 68% nucleotide sequence identity to Thogoto virus (segment 2; ∼74% at the amino acid level) and a more distant relationship to Dhori virus, the two prototype viruses of the recognized species of the genus Thogotovirus. Despite sequence similarity, the coding potentials of UPOV and ABV differed from that of Thogoto virus, instead being like that of Dhori virus. Our findings suggest that the tick-transmitted viruses UPOV and ABV represent geographically distinct viruses in the genus Thogotovirus of the family Orthomyxoviridae that do not fit in the two currently recognized species of this genus. IMPORTANCE Upolu virus (UPOV) and Aransas Bay virus (ABV) are shown to be orthomyxoviruses instead of bunyaviruses, as previously thought. Genetic characterization and adequate classification of agents are paramount in this molecular age to devise appropriate surveillance and diagnostics. Although more closely related to Thogoto virus by sequence, UPOV and ABV differ in their coding potentials by lacking a proposed pathogenicity factor. In this respect, they are similar to Dhori virus, which, despite the lack of a pathogenicity factor, can cause disease. These findings enable further studies into the evolution and pathogenicity of orthomyxoviruses.
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Genomic and antigenic characterization of Jos virus
Journal of General Virology, 2012Co-Authors: Ana Valeria Bussetti, Amelia P. A. Travassos Da Rosa, Robert B. Tesh, Vsevolod L. Popov, Stephen K. Hutchison, Gustavo Palacios, Nazir Savji, Komal Jain, Hilda Guzman, W. Ian LipkinAbstract:Jos virus (JOSV), originally isolated in Jos, Nigeria in 1967, has remained unclassified despite cultivation in tissue culture, development of animal models of infection and implementation of seroprevalence surveys for infection. Here, we report genetic, ultrastructural and serological evidence that JOSV is an orthomyxovirus distinct from but phylogenetically related to viruses of the genus Thogotovirus.
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Short Communication Genomic and antigenic characterization of Jos virus
2012Co-Authors: Ana Valeria Bussetti, Amelia P. A. Travassos Da Rosa, Robert B. Tesh, Vsevolod L. Popov, Stephen K. Hutchison, Gustavo Palacios, Nazir Savji, Komal Jain, Hilda Guzman, W. Ian LipkinAbstract:454 Life Sciences, A Roche Company, Branford, CT, USAJos virus (JOSV), originally isolated in Jos, Nigeria in 1967, has remained unclassified despitecultivation in tissue culture, development of animal models of infection and implementation ofseroprevalence surveys for infection. Here, we report genetic, ultrastructural and serologicalevidence that JOSV is an orthomyxovirus distinct from but phylogenetically related to viruses ofthe genus Thogotovirus.
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dhori virus orthomyxoviridae Thogotovirus infection of mice produces a disease and cytokine response pattern similar to that of highly virulent influenza a h5n1 virus infection in humans
American Journal of Tropical Medicine and Hygiene, 2008Co-Authors: Nan Wang, Robert B. Tesh, Hilda Guzman, Elena Sbrana, Tomoki Yoshikawa, Chientek Tseng, Shu-yuan XiaoAbstract:Mice infected with Dhori virus (DHOV) develop a fulminant, systemic, and uniformly fatal illness that has many of the clinical and pathologic findings seen in H5N1 influenza A virus infection. However, the role of host's immune response in DHOV infection remains unclear. In this study, the concentrations of 23 inflammatory cytokines and chemokines were measured in the liver, lungs, and sera of mice during the course of DHOV infection. Liver function, level of viremia, and hematologic response were also monitored. Infected animals exhibited significant leu- copenia and lymphopenia, which directly correlated with the disease progression. High yields of infectious virus along with strikingly elevated expression of various inflammatory mediators, including tumor necrosis factor (TNF)-, inter- leukin (IL)-1, IL-6, IL-10, macrophage inflammatory protein (MIP)-1, manocyte chemoattractant protein (MCP)-1, and interferon (IFN)-, indicate that these responses play an important role in the observed disease and pathology. The overall clinical, pathologic, and immunologic responses of ICR mice to DHOV infection closely resemble those de- scribed for highly virulent influenza A virus infection in humans, thereby offering a realistic, safe, and alternative animal model for studying the pathogenesis and treatment of highly pathogenic avian influenza virus.
Georg Kochs - One of the best experts on this subject based on the ideXlab platform.
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Tick-transmitted Thogotovirus gains high virulence by a single MxA escape mutation in the viral nucleoprotein.
PLoS pathogens, 2020Co-Authors: Jonas Fuchs, Alexander Oschwald, Laura Graf, Georg KochsAbstract:Infections with emerging and re-emerging arboviruses are of increasing concern for global health. Tick-transmitted RNA viruses of the genus Thogotovirus in the Orthomyxoviridae family have considerable zoonotic potential, as indicated by the recent emergence of Bourbon virus in the USA. To successfully infect humans, arboviruses have to escape the restrictive power of the interferon defense system. This is exemplified by the high sensitivity of Thogotoviruses to the antiviral action of the interferon-induced myxovirus resistance protein A (MxA) that inhibits the polymerase activity of incoming viral ribonucleoprotein complexes. Acquiring resistance to human MxA would be expected to enhance the zoonotic potential of these pathogens. Therefore, we screened a panel of 10 different Thogotovirus isolates obtained from various parts of the world for their sensitivity to MxA. A single isolate from Nigeria, Jos virus, showed resistance to the antiviral action of MxA in cell culture and in MxA-transgenic mice, whereas the prototypic Sicilian isolate SiAr126 was fully MxA-sensitive. Further analysis identified two amino acid substitutions (G327R and R328V) in the viral nucleoprotein as determinants for MxA resistance. Importantly, when introduced into SiAr126, the R328V mutation resulted in complete MxA escape of the recombinant virus, without causing any viral fitness loss. The escape mutation abolished viral nucleoprotein recognition by MxA and allowed unhindered viral growth in MxA-expressing cells and in MxA-transgenic mice. These findings demonstrate that Thogotoviruses can overcome the species barrier by escaping MxA restriction and reveal that these tick-transmitted viruses may have a greater zoonotic potential than previously suspected.
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Combinatorial mutagenesis of rapidly evolving residues yields super-restrictor antiviral proteins.
PLoS biology, 2019Co-Authors: Rossana Colón-thillet, Laura Graf, Georg Kochs, Emily Hsieh, Richard N. Mclaughlin, Janet M. Young, Michael Emerman, Harmit S. MalikAbstract:Antagonistic interactions drive host–virus evolutionary arms races, which often manifest as recurrent amino acid changes (i.e., positive selection) at their protein–protein interaction interfaces. Here, we investigated whether combinatorial mutagenesis of positions under positive selection in a host antiviral protein could enhance its restrictive properties. We tested approximately 700 variants of human MxA, generated by combinatorial mutagenesis, for their ability to restrict Thogotovirus (THOV). We identified MxA super-restrictors with increased binding to the THOV nucleoprotein (NP) target protein and 10-fold higher anti-THOV restriction relative to wild-type human MxA, the most potent naturally occurring anti-THOV restrictor identified. Our findings reveal a means to elicit super-restrictor antiviral proteins by leveraging signatures of positive selection. Although some MxA super-restrictors of THOV were impaired in their restriction of H5N1 influenza A virus (IAV), other super-restrictor variants increased THOV restriction without impairment of IAV restriction. Thus, broadly acting antiviral proteins such as MxA mitigate breadth-versus-specificity trade-offs that could otherwise constrain their adaptive landscape.
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Comparative structural and functional analysis of orthomyxovirus polymerase cap-snatching domains.
PLoS ONE, 2013Co-Authors: Delphine Guilligay, Georg Kochs, Jan Kadlec, Thibaut Crépin, Thomas Lunardi, Denis Bouvier, Rob W H Ruigrok, Stephen CusackAbstract:Orthomyxovirus Influenza A virus (IAV) heterotrimeric polymerase performs transcription of viral mRNAs by cap-snatching, which involves generation of capped primers by host pre-mRNA binding via the PB2 subunit cap-binding site and cleavage 10-13 nucleotides from the 5' cap by the PA subunit endonuclease. Thogotoviruses, tick-borne orthomyxoviruses that includes Thogoto (THOV), Dhori (DHOV) and Jos (JOSV) viruses, are thought to perform cap-snatching by cleaving directly after the cap and thus have no heterogeneous, host-derived sequences at the 5' extremity of their mRNAs. Based on recent work identifying the cap-binding and endonuclease domains in IAV polymerase, we determined the crystal structures of two THOV PB2 domains, the putative cap-binding and the so-called '627-domain', and the structures of the putative endonuclease domains (PA-Nter) of THOV and DHOV. Despite low sequence similarity, corresponding domains have the same fold confirming the overall architectural similarity of orthomyxovirus polymerases. However the putative Thogotovirus cap-snatching domains in PA and PB2 have non-conservative substitutions of key active site residues. Biochemical analysis confirms that, unlike the IAV domains, the THOV and DHOV PA-Nter domains do not bind divalent cations and have no endonuclease activity and the THOV central PB2 domain does not bind cap analogues. On the other hand, sequence analysis suggests that other, non-influenza, orthomyxoviruses, such as salmon anemia virus (isavirus) and Quaranfil virus likely conserve active cap-snatching domains correlating with the reported occurrence of heterogeneous, host-derived sequences at the 5' end of the mRNAs of these viruses. These results highlight the unusual nature of transcription initiation by Thogotoviruses.
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The fourth genus in the Orthomyxoviridae: sequence analyses of two Thogoto virus polymerase proteins and comparison with influenza viruses
Virus Research, 1997Co-Authors: Michael B. Leahy, Georg Kochs, Friedemann Weber, Johannes T. Dessens, Patricia A. NuttallAbstract:Abstract The tick-borne Thogoto virus (THOV) is the type species of a newly recognized fourth genus, Thogotovirus, in the family Orthomyxoviridae . Because of the distant relationship of THOV with the influenza viruses, determination of its genomic information can potentially be used to identify important domains in influenza virus proteins. We have determined the complete nucleotide sequence of the second longest RNA segment of THOV. The molecule comprises 2212 nucleotides with a single large open reading frame encoding a protein of 710 amino acids, estimated M r 81 284. The protein shares 77% amino acid similarity with the PB1-like protein of Dhori virus, a related tick-borne virus, and 50–53% with the PB1 polymerase proteins of influenza virus A, B and C. All the motifs characteristic of RNA-dependent polymerases were identified including the SSDD motif common to all RNA-dependant RNA polymerases, indicating that the THOV protein is functionally analogous to the influenza virus PB1 proteins and involved in chain elongation. We also report the corrected sequence of the third longest RNA segment of THOV, encoding a protein which shares 44–47% amino acid similarity with the PA-like polymerase proteins of influenza virus A, B and C. The biological significance of conserved domains in these orthomyxovirid proteins is discussed.
Amelia P. A. Travassos Da Rosa - One of the best experts on this subject based on the ideXlab platform.
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Upolu virus and Aransas Bay virus, Two Presumptive Bunyaviruses, Are Novel Members of the Family Orthomyxoviridae
Journal of Virology, 2014Co-Authors: Thomas Briese, Amelia P. A. Travassos Da Rosa, Robert B. Tesh, Vsevolod L. Popov, Rashmi Chowdhary, Stephen K. Hutchison, Craig Street, W. Ian LipkinAbstract:UNLABELLED Emerging and zoonotic pathogens pose continuing threats to human health and ongoing challenges to diagnostics. As nucleic acid tests are playing increasingly prominent roles in diagnostics, the genetic characterization of molecularly uncharacterized agents is expected to significantly enhance detection and surveillance capabilities. We report the identification of two previously unrecognized members of the family Orthomyxoviridae, which includes the influenza viruses and the tick-transmitted Thogoto and Dhori viruses. We provide morphological, serologic, and genetic evidence that Upolu virus (UPOV) from Australia and Aransas Bay virus (ABV) from North America, both previously considered potential bunyaviruses based on electron microscopy and physicochemical features, are orthomyxoviruses instead. Their genomes show up to 68% nucleotide sequence identity to Thogoto virus (segment 2; ∼74% at the amino acid level) and a more distant relationship to Dhori virus, the two prototype viruses of the recognized species of the genus Thogotovirus. Despite sequence similarity, the coding potentials of UPOV and ABV differed from that of Thogoto virus, instead being like that of Dhori virus. Our findings suggest that the tick-transmitted viruses UPOV and ABV represent geographically distinct viruses in the genus Thogotovirus of the family Orthomyxoviridae that do not fit in the two currently recognized species of this genus. IMPORTANCE Upolu virus (UPOV) and Aransas Bay virus (ABV) are shown to be orthomyxoviruses instead of bunyaviruses, as previously thought. Genetic characterization and adequate classification of agents are paramount in this molecular age to devise appropriate surveillance and diagnostics. Although more closely related to Thogoto virus by sequence, UPOV and ABV differ in their coding potentials by lacking a proposed pathogenicity factor. In this respect, they are similar to Dhori virus, which, despite the lack of a pathogenicity factor, can cause disease. These findings enable further studies into the evolution and pathogenicity of orthomyxoviruses.
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Genomic and antigenic characterization of Jos virus
Journal of General Virology, 2012Co-Authors: Ana Valeria Bussetti, Amelia P. A. Travassos Da Rosa, Robert B. Tesh, Vsevolod L. Popov, Stephen K. Hutchison, Gustavo Palacios, Nazir Savji, Komal Jain, Hilda Guzman, W. Ian LipkinAbstract:Jos virus (JOSV), originally isolated in Jos, Nigeria in 1967, has remained unclassified despite cultivation in tissue culture, development of animal models of infection and implementation of seroprevalence surveys for infection. Here, we report genetic, ultrastructural and serological evidence that JOSV is an orthomyxovirus distinct from but phylogenetically related to viruses of the genus Thogotovirus.
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Short Communication Genomic and antigenic characterization of Jos virus
2012Co-Authors: Ana Valeria Bussetti, Amelia P. A. Travassos Da Rosa, Robert B. Tesh, Vsevolod L. Popov, Stephen K. Hutchison, Gustavo Palacios, Nazir Savji, Komal Jain, Hilda Guzman, W. Ian LipkinAbstract:454 Life Sciences, A Roche Company, Branford, CT, USAJos virus (JOSV), originally isolated in Jos, Nigeria in 1967, has remained unclassified despitecultivation in tissue culture, development of animal models of infection and implementation ofseroprevalence surveys for infection. Here, we report genetic, ultrastructural and serologicalevidence that JOSV is an orthomyxovirus distinct from but phylogenetically related to viruses ofthe genus Thogotovirus.
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Dhori virus (Orthomyxoviridae: Thogotovirus) infection in mice: A model of the pathogenesis of severe orthomyxovirus infection
The American Journal of Tropical Medicine and Hygiene, 2007Co-Authors: Rosa I. Mateo, Amelia P. A. Travassos Da Rosa, Shu-yuan Xiao, Hao Lei, Robert B. TeshAbstract:After intranasal, subcutaneous, or intraperitoneal infection with Dhori virus (DHOV), adult mice developed a fulminant and uniformly fatal illness with many of the clinical and pathologic findings seen in mice infected with H5N1 highly pathogenic avian influenza A virus. Histopathologic findings in lungs of DHOV-infected mice consisted of hemorrhage, inflammation, and thickening of the interstitium and the alveolar septa and alveolar edema. Extra-pulmonary findings included hepatocellular necrosis and steatosis, widespread severe fibrinoid necrosis in lymphoid organs, marked lymphocyte loss and karyorrhexis, and neuronal degeneration in brain. Similar systemic histopathologic findings have been reported in the few fatal human H5N1 cases examined at autopsy. Because of the relationship of DHOV to the influenza viruses, its biosafety level 2 status, and its similar pathology in mice, the DHOV-mouse model may offer a low-cost, relatively safe, and realistic animal model for studies on the pathogenesis and management of H5N1 virus infection.
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ARAGUARI VIRUS, A NEW MEMBER OF THE FAMILY ORTHOMYXOVIRIDAE: SEROLOGIC, ULTRASTRUCTURAL, AND MOLECULAR CHARACTERIZATION
The American Journal of Tropical Medicine and Hygiene, 2005Co-Authors: Eliana Vieira Pinto Da Silva, Amelia P. A. Travassos Da Rosa, Márcio Roberto Teixeira Nunes, José Antonio Picanço Diniz, Robert B. Tesh, Ana Cecília Ribeiro Cruz, Conceição De Maria Almeida Vieira, Pedro Fernando Da Costa VasconcelosAbstract:This paper reports the results of serologic, structural, biochemical, and genetic studies indicating that Araguari virus, a previously unassigned viral agent, is a member of the family Orthomyxoviridae and genus Thogotovirus. Araguari virus has six RNA fragments; biologically, it shares several properties with other viruses in the family Orthomyxoviridae. Nucleotide sequencing of the RNA segments 4 (glycoprotein) and 5 (nucleoprotein) of Araguari virus aligned with the orthomyxoviruses, showing the closest relationship with Thogoto virus (sequence similarity = 61.9% and 69.1%, respectively, for glycoprotein and nucleoprotein), but also sharing a more distant similarity with Dhori and Influenza C viruses, especially for the glycoprotein gene. Based on these results, we propose that Araguari virus should be assigned as a new member of the family Orthomyxoviridae and genus Thogotovirus.
Sarah Temmam - One of the best experts on this subject based on the ideXlab platform.
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Tick-borne pathogens detection in Caribbean ticks using high-throughput microfluidic real-time PCR (DOMOTICK Project). [C5]
2017Co-Authors: Mathilde Gondard, Sarah Temmam, Sabine Delannoy, Elodie Devillers, Valérie Pinarello, Rosalie Aprelon, Marc Eloit, Muriel Vayssier-taussat, Emmanuel Albina, Sara MoutaillerAbstract:Among hematophagous arthropods, ticks transmit the greater variety of pathogens of public health and veterinary importance whose (re)-emergence is recognized worldwide. Whereas the main human and animal tick-borne pathogens are well characterised in the Northern hemisphere, very few is known concerning the diversity of tick species and tick-borne pathogens circulating within the Neotropical zone of the Americas, especially concerning the Caribbean area. Most of the epidemiological data on the topic are based on old records and focused on the main livestock pathogens such as Ehrlichia ruminantium, Babesia (bovis and bigemina) and Anaplasma marginale. These observations underline the need to develop high throughput diagnosis methods that will allow us to conduct large scale epidemiological surveys required to better anticipate the risk of (re)-emergence of tick-borne disease in such areas. In this context, the DOMOTICK project was designed to develop a new high-throughput real-time PCR method for a large scale screening of tick-borne pathogens potentially circulating in the Caribbean. This technology is based on high-throughput microfluidic real-time PCRs using Taqman probes (BioMarkTM dynamic arrays, Fluidigm Corporation), allowing the simultaneous detection of up to 95 pathogens across 95 samples of ticks (Michelet et al, 2014). The choice of pathogens included in this new high-throughput technology was based on a comprehensive analysis of the literature, and on a without a priori detection of new or unsuspected pathogens by RNA-sequencing on nucleic acids extracted from ticks collected in Guadeloupe and Martinique. NGS analysis suggests that these ticks may harbour more pathogenic microorganisms than the currently monitored in the Caribbean, such as Rickettsia and Borrelia species of public health importance. Up to now, 40 bacterial species have been listed, including the genera Anaplasma, Ehrlichia, Bartonella, Borrelia, Rickettsia, Mycoplasma, Francisella, Coxiella, Aegyptianella ; 14 parasites species, belonging to the genera Babesia, Theleria, Hepatozoon, Leishmania, Rangelia vitalii, Cytauxzoon felis ; and 32 arboviruses mainly belonging to viral genus of Orthobunyavirus, Phlebovirus, Nairovirus, Asfivivirus, Thogotovirus, Flavivirus, Coltivirus and Orbivirus. The high-throughput real-time PCR technology developed here have been validated on tick samples collected in Guadeloupe and Martinique. Finally, this new high throughput method will allow exploratory epidemiological studies on tick-borne pathogens circulating within Caribbean ticks collected on various vertebrate hosts through some Caribbean islands, such as Trinidad and Tobago, St Kitts, Barbados, St Lucia, and Cuba, thanks to the CaribVet network, and to local veterinarians. (Resume d'auteur)
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Characterization of Viral Communities of Biting Midges and Identification of Novel Thogotovirus Species and Rhabdovirus Genus
Viruses, 2016Co-Authors: Sarah Temmam, Sonia Monteil-bouchard, Noemie Labas, Maxence Aubadie-ladrix, Catherine Robert, Masse Sambou, Oleg Mediannikov, Jean-pierre Baudoin, Didier Raoult, Christelle DesnuesAbstract:More than two thirds of emerging viruses are of zoonotic origin, and among them RNA viruses represent the majority. Ceratopogonidae (genus Culicoides) are well-known vectors of several viruses responsible for epizooties (bluetongue, epizootic haemorrhagic disease, etc.). They are also vectors of the only known virus infecting humans: the Oropouche virus. Female midges usually feed on a variety of hosts, leading to possible transmission of emerging viruses from animals to humans. In this context, we report here the analysis of RNA viral communities of Senegalese biting midges using next-generation sequencing techniques as a preliminary step toward the identification of potential viral biohazards. Sequencing of the RNA virome of three pools of Culicoides revealed the presence of a significant diversity of viruses infecting plants, insects and mammals. Several novel viruses were detected, including a novel Thogotovirus species, related but genetically distant from previously described tick-borne Thogotoviruses. Novel rhabdoviruses were also detected, possibly constituting a novel Rhabdoviridae genus, and putatively restricted to insects. Sequences related to the major viruses transmitted by Culicoides, i.e., African horse sickness, bluetongue and epizootic haemorrhagic disease viruses were also detected. This study highlights the interest in monitoring the emergence and circulation of zoonoses and epizooties using their arthropod vectors.