title: Novel activities by ebolavirus and marburgvirus interferon antagonists revealed using a standardized in vitro reporter system.
abstract: Filoviruses are highly lethal in humans and nonhuman primates, likely due to potent antagonism of host interferon (IFN) responses early in infection. Filoviral protein VP35 is implicated as the major IFN induction antagonist, while Ebola virus (EBOV) VP24 or Marburg virus (MARV) VP40 are known to block downstream IFN signaling. Despite progress elucidating EBOV and MARV antagonist function, those for most other filoviruses, including Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV), Bundibugyo (BDBV) and Ravn (RAVV) viruses, remain largely neglected. Thus, using standardized vectors and reporter assays, we characterized activities by each IFN antagonist from all known ebolavirus and marburgvirus species side-by-side. We uncover noncanonical suppression of IFN induction by ebolavirus VP24, differing potencies by MARV and RAVV proteins, and intriguingly, weaker antagonism by VP24 of RESTV. These underlying molecular explanations for differential virulence in humans could guide future investigations of more-neglected filoviruses as well as treatment and vaccine studies.
authors.affiliation: Viral Special Pathogens Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Guito
authors.affiliation: Viral Special Pathogens Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.
authors.forename: César G
authors.initials: CG
authors.lastname: Albariño
authors.affiliation: Viral Special Pathogens Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.
authors.forename: Ayan K
authors.initials: AK
authors.lastname: Chakrabarti
authors.affiliation: Viral Special Pathogens Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States. Electronic address: jit8@cdc.gov.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Towner
mesh_terms: D000818:Animals; D029043:Ebolavirus / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D019142:Hemorrhagic Fever, Ebola / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008379:Marburg Virus Disease / Q000821:virology*; D029024:Marburgvirus / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; D007372:Interferons
keywords: Ebolavirus; Filoviral interferon antagonists; Filoviruses; Innate immune response; Interferon pathway; Marburgvirus; Neglected pathogens; Viral immune evasion; Viral protein function; Virus-host interactions