title: MAVS-mediated host cell defense is inhibited by Borna disease virus.
abstract: Viruses often have strategies for preventing host cell apoptosis, which antagonizes viral replication. Borna disease virus (BDV) is a neurotropic RNA virus that establishes a non-cytolytic persistent infection. Although BDV suppresses type I Interferon (IFN) through (TANK)-binding kinase 1 (TBK-1) associated BDV P protein, it is still unclear how BDV can survive in the host cell and establish a persistent infection. Recently, it has been recognized that mitochondria-mediated apoptosis through the mitochondrial antiviral signaling protein (MAVS) and the RIG-I-like receptor (RLR) signaling pathway is a crucial component of the innate immune response. In this work we show that BDV X protein colocalizes and interacts with MAVS in the mitochondria to block programmed cell death. BDV X protein-mediated inhibition of apoptosis was independent of type I IFN production and NF-κB activity. The reduction of BDV X expression with RNA interference (RNAi) or the mutation of BDV X enhanced MAVS-induced cell death. Collectively, our data provide novel insights into how BDV X protein inhibits antiviral-associated programmed cell death, through its action of MAVS function.
authors.affiliation: The Heilongjiang Key Laboratory of Immunity and Infection, Key Laboratory of Pathogenic Biology Heilongjiang Higher Education Institutions, Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Li
authors.forename: Wuqi
authors.initials: W
authors.lastname: Song
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Qingmeng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Junming
authors.initials: J
authors.lastname: He
authors.forename: Aimei
authors.initials: A
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.forename: Aixia
authors.initials: A
authors.lastname: Zhai
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Hu
authors.forename: Wenping
authors.initials: W
authors.lastname: Kao
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wei
authors.forename: Fengmin
authors.initials: F
authors.lastname: Zhang
authors.forename: Dakang
authors.initials: D
authors.lastname: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D001891:Borna disease virus / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016328:NF-kappa B; D014764:Viral Proteins; D016899:Interferon-beta; D020169:Caspases
keywords: Apoptosis; BDV; Borna disease virus; HCMV; HCV; HSV; Host cell defense; IFN; IRF; LCMV; MAVS; Mitochondria; Mitochondrial antiviral signaling protein; NF-κB; PARP-1; PRRs; RIG-I-like helicases; RIG-I-like receptor; RLH; RLR; RNA interference; RNAi; TANK-binding kinase 1; TBK-1; TLRs; Toll-like receptors; hepatitis C virus; herpes simplex virus; human cytomegalovirus; interferon; interferon regulatory factor; lymphocytic choriomeningitis virus; mitochondrial antiviral signaling protein; nuclear factor kappa-B; pathogen recognition receptors; poly (ADP-Ribose) polymerase 1; shRNA; short hairpin RNA