title: Antiviral protection against enterovirus 71 mediated by autophagy induction following FLICE-inhibitory protein inactivation.
abstract: Even with the recent awareness of enterovirus 71 (EV71) as a major public health issue, there are no preventive or therapeutic agents that are effective against EV71 infection. Although FLICE-like inhibitory protein (FLIP) has been identified as a factor that modulates virus pathogenesis, there are no reports regarding its effects on EV71 infection. The aim of the present study was to identify whether FLIP influences EV71 pathogenesis and to understand the underlying mechanisms. Virus replication was markedly reduced in MRC5 cells preincubated with anti-FLIP peptides, and infected cells were rescued from the cytopathic effects of the virus. The anti-FLIP peptides induced autophagy by disrupting intrinsic FLIP functions. The antiviral activity of these peptides was reduced when autophagy was inhibited by treatment with siRNA targeted to beclin-1. Thus, the present study provides evidence that anti-FLIP peptides induce autophagy by inactivating cFLIP, and that this is associated with antiviral effects against EV71.
authors.affiliation: Department of Microbiology, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Minah
authors.initials: M
authors.lastname: Won
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Jun
authors.forename: Maria
authors.initials: M
authors.lastname: Khim
authors.forename: Sang Hyup
authors.initials: SH
authors.lastname: Hong
authors.forename: Nung Hwa
authors.initials: NH
authors.lastname: Park
authors.forename: Yoo Kyum
authors.initials: YK
authors.lastname: Kim
authors.forename: Heuiran
authors.initials: H
authors.lastname: Lee
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism; D001343:Autophagy; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D029821:Enterovirus A, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D010455:Peptides / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D010455:Peptides