title: Over-expression of mitochondrial antiviral signaling protein inhibits coxsackievirus B3 infection by enhancing type-I interferons production.
abstract: BACKGROUND
  Recent studies have revealed that Mitochondrial Antiviral Signaling (MAVS) protein plays an essential role in the inhibition of viral infection through type I interferon (IFN) pathway. It has been shown that 3C (pro) cysteine protease of coxsackievirus B3 (CVB3) cleaves MAVS to inhibit type I IFNs induction. Other workers also found that MAVS knock-out mice suffered CVB3 susceptibility and severe histopathological change. Accordingly,our experiments were designed to explore the protection of over-expressing MAVS against CVB3 infection and the possible mechanism.
  
  
  RESULTS
  In this study, HeLa cells (transfected with MAVS constructs pre- or post- exposure to CVB3) were used to analyze the function of exogenous MAVS on CVB3 infection. The results revealed that though CVB3 infection induced production of type I IFNs, viral replication and cell death were not effectively inhibited. Similarly, exogenous MAVS increased type I IFNs moderately. Morever, we observed robust production of type I IFNs in CVB3 post-infected HeLa cells thereby successfully inhibiting CVB3 infection, as well formation of cytopathic effect (CPE) and cell death. Finally, introduction of exogenous MAVS into CVB3 pre-infected cells also restricted viral infection efficiently by greatly up-regulating IFNs.
  
  
  CONCLUSIONS
  In summary, exogenous MAVS effectively prevents and controls CVB3 infection by modulating and promoting the production of type I IFNs. The IFNs level in MAVS over-expressing cells is still tightly regulated by CVB3 infection. Thus, the factors that up-regulate MAVS might be an alternative prescription in CVB3-related syndromes by enhancing IFNs production.
authors.affiliation: Key Laboratory of Immunity and Infection, Pathogenic Biology, Heilongjiang province, Department of Microbiology, Harbin Medical University, 150081, Harbin, People's Republic of China.
authors.forename: Qing-Meng
authors.initials: QM
authors.lastname: Zhang
authors.forename: Wu-Qi
authors.initials: WQ
authors.lastname: Song
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.forename: Ai-Xia
authors.initials: AX
authors.lastname: Zhai
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Ai-Mei
authors.initials: AM
authors.lastname: Li
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: He
authors.forename: Jin-Yun
authors.initials: JY
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Lan-Lan
authors.initials: LL
authors.lastname: Wei
authors.forename: Feng-Min
authors.initials: FM
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003384:Coxsackievirus Infections / Q000235:genetics* / Q000378:metabolism*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D029822:Enterovirus B, Human / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007370:Interferon Type I; C505371:MAVS protein, human