title: Filoviral immune evasion mechanisms.
abstract: The Filoviridae family of viruses, which includes the genera Ebolavirus (EBOV) and Marburgvirus (MARV), causes severe and often times lethal hemorrhagic fever in humans. Filoviral infections are associated with ineffective innate antiviral responses as a result of virally encoded immune antagonists, which render the host incapable of mounting effective innate or adaptive immune responses. The Type I interferon (IFN) response is critical for establishing an antiviral state in the host cell and subsequent activation of the adaptive immune responses. Several filoviral encoded components target Type I IFN responses, and this innate immune suppression is important for viral replication and pathogenesis. For example, EBOV VP35 inhibits the phosphorylation of IRF-3/7 by the TBK-1/IKKε kinases in addition to sequestering viral RNA from detection by RIG-I like receptors. MARV VP40 inhibits STAT1/2 phosphorylation by inhibiting the JAK family kinases. EBOV VP24 inhibits nuclear translocation of activated STAT1 by karyopherin-α. The examples also represent distinct mechanisms utilized by filoviral proteins in order to counter immune responses, which results in limited IFN-α/β production and downstream signaling.
authors: Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
authors: Parameshwaran
authors: P
authors: Ramanan
authors: Reed S
authors: RS
authors: Shabman
authors: Craig S
authors: CS
authors: Brown
authors: Gaya K
authors: GK
authors: Amarasinghe
authors: Christopher F
authors: CF
authors: Basler
authors: Daisy W
authors: DW
authors: Leung
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D029043:Ebolavirus / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology* / Q000821:virology; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007113:Immunity, Innate; D007370:Interferon Type I / Q000378:metabolism; D008379:Marburg Virus Disease / Q000276:immunology* / Q000821:virology; D029024:Marburgvirus / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D010766:Phosphorylation; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; D014764:Viral Proteins