title: Recombinant Marburg viruses containing mutations in the IID region of VP35 prevent inhibition of Host immune responses.
abstract: Previous in vitro studies have demonstrated that Ebola and Marburg virus (EBOV and MARV) VP35 antagonize the host cell immune response. Moreover, specific mutations in the IFN inhibitory domain (IID) of EBOV and MARV VP35 that abrogate their interaction with virus-derived dsRNA, lack the ability to inhibit the host immune response. To investigate the role of MARV VP35 in the context of infectious virus, we used our reverse genetics system to generate two recombinant MARVs carrying specific mutations in the IID region of VP35. Our data show that wild-type and mutant viruses grow to similar titers in interferon deficient cells, but exhibit attenuated growth in interferon-competent cells. Furthermore, in contrast to wild-type virus, both MARV mutants were unable to inhibit expression of various antiviral genes. The MARV VP35 mutants exhibit similar phenotypes to those previously described for EBOV, suggesting the existence of a shared immune-modulatory strategy between filoviruses.
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, USA.
authors.forename: César G
authors.initials: CG
authors.lastname: Albariño
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wiggleton Guerrero
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, USA.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Spengler
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, USA.
authors.forename: Luke S
authors.initials: LS
authors.lastname: Uebelhoer
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, USA.
authors.forename: Ayan K
authors.initials: AK
authors.lastname: Chakrabarti
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, USA.
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, USA. Electronic address: jit8@cdc.gov.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Towner
mesh_terms: D000818:Animals; D002460:Cell Line; D054884:Host-Pathogen Interactions; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D008379:Marburg Virus Disease / Q000276:immunology* / Q000821:virology; D029024:Marburgvirus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D017434:Protein Structure, Tertiary; D014758:Viral Core Proteins / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology
chemical_list: D014758:Viral Core Proteins; D016899:Interferon-beta
keywords: Bat virus; Central basic; Ebola virus; Filovirus; IFN-antagonism; Immune-modulatory; Marburg virus; Patch; VP35