title: Inhibition of interleukin-6 expression by the V protein of parainfluenza virus 5.
abstract: The V protein of parainfluenza virus 5 (PIV5) plays an important role in the evasion of host immune responses. The V protein blocks interferon (IFN) signaling in human cells by causing degradation of the STAT1 protein, a key component of IFN signaling, and blocks IFN-beta production by preventing nuclear translocation of IRF3, a key transcription factor for activating IFN-beta promoter. Interleukin-6 (IL-6), along with tumor necrosis factor (TNF)-alpha and IL-1beta, is a major proinflammatory cytokine that plays important roles in clearing virus infection through inflammatory responses. Many viruses have developed strategies to block IL-6 expression. Wild-type PIV5 infection induces little, if any, expression of cytokines such as IL-6 or TNF-alpha, whereas infection by a mutant PIV5 lacking the conserved C-terminal cysteine rich domain (rPIV5VDeltaC) induced high levels of IL-6 expression. Examination of mRNA levels of IL-6 indicated that the transcription activation of IL-6 played an important role in the increased IL-6 expression. Co-infection with wild-type PIV5 prevented the activation of IL-6 transcription by rPIV5VDeltaC, and a plasmid encoding the full-length PIV5 V protein prevented the activation of IL-6 promoter-driven reporter gene expression by rPIV5VDeltaC, indicating that the V protein played a role in inhibiting IL-6 transcription. The activation of IL-6 was independent of IFN-beta even though rPIV5VDeltaC-infected cells produced IFN-beta. Using reporter gene assays and chromatin immunoprecipitation (ChIP), it was found that NF-kappaB played an important role in activating expression of IL-6. We have proposed a model of activating and inhibiting IL-6 transcription by PIV5.
authors: Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors: Yuan
authors: Y
authors: Lin
authors: Minghao
authors: M
authors: Sun
authors: Sandra M
authors: SM
authors: Fuentes
authors: Celia D
authors: CD
authors: Keim
authors: Terri
authors: T
authors: Rothermel
authors: Biao
authors: B
authors: He
mesh_terms: D000818:Animals; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D045402:Parainfluenza Virus 5 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; C097019:V protein, Simian parainfluenza virus 5; D015678:Viral Structural Proteins
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