title: Enterovirus 71 blocks selectively type I interferon production through the 3C viral protein in mice.
abstract: Type I interferons (IFNs) represent an essential innate defense mechanism for controlling enterovirus 71 (EV 71) infection. Mice inoculated with EV 71 produced a significantly lower amount of type I IFNs than those inoculated with poly (I:C), adenovirus type V, or coxsackievirus B3 (CB3). EV 71 infection, however, mounted a proinflammatory response with a significant increase in the levels of serum and brain interleukin (IL)-6, monocyte chemoattractant protein-1, tumor necrosis factor, and IFN-γ. EV 71 infection abolished both poly (I:C)- and CB3-induced type I IFN production of mice. Such effect was not extended to other enteroviruses including coxsackievirus A24, B2, B3, and echovirus 9, as mice infected with these viruses retained type I IFN responsiveness upon poly (I:C) challenge. In addition, EV 71-infected RAW264.7 cells produced significantly lower amount of type I IFNs than non-infected cells upon poly (I:C) stimulation. The inhibitory effect of EV 71 on type I IFN production was attributed to the viral protein 3C, which was confirmed using over-expression systems in both mice and RAW264.7 cells. The 3C over-expression, however, did not interfere with poly (I:C)-induced proinflammatory cytokine production. These findings indicate that EV 71 can hamper the host innate defense by blocking selectively type I IFN synthesis through the 3C viral protein.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Lee
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Wang
authors.forename: Jen-Ren
authors.initials: JR
authors.lastname: Wang
authors.forename: Szu-Wei
authors.initials: SW
authors.lastname: Huang
authors.forename: Chun-Keung
authors.initials: CK
authors.lastname: Yu
mesh_terms: D000086042:3C Viral Proteases; D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D029821:Enterovirus A, Human / Q000276:immunology* / Q000472:pathogenicity*; D057131:Immune Evasion; D007108:Immune Tolerance; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D014764:Viral Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D014764:Viral Proteins; D037521:Virulence Factors; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases