The V proteins of simian virus 5 and other paramyxoviruses inhibit induction of interferon-beta.
In this article we show that the paramyxovirus SV5 is a poor inducer of interferon-beta (IFN-beta). This inefficient induction is a consequence of the expression of an intact viral V protein. In the absence of the viral V protein cysteine-rich C-terminal domain, IFN-beta mRNA is strongly induced and the transcription factors NF-kappaB and IRF-3 are activated significantly. The V protein can work in isolation from SV5 to block intracellular dsRNA signaling. The mechanism of block to dsRNA signaling is distinct from that previously observed for blocking IFN signaling in that proteolysis of candidate factors cannot be detected, and furthermore, the respective blocks require distinct protein domains. Blocking of the induction of IFN-beta by dsRNA requires the C-terminal cysteine-rich domain, a feature that is highly conserved among paramyxoviruses. We demonstrate that the V proteins from other paramyxoviruses have equivalent functions and speculate that limiting the yield of IFN-beta during infection may be a general property of paramyxoviruses.
Poole
Emma
E
Department of Biochemistry and Immunology, St. George's Hospital Medical School, University of London, London, SW17 0RE, United Kingdom.
He
Biao
B
Lamb
Robert A
RA
Randall
Richard E
RE
Goodbourn
Stephen
S
D000818:Animals; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D018108:Respirovirus / Q000276:immunology / Q000502:physiology*; D010253:Respirovirus Infections / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D015678:Viral Structural Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012367:RNA, Viral; D014157:Transcription Factors; C097019:V protein, Simian parainfluenza virus 5; D015678:Viral Structural Proteins; D016899:Interferon-beta; D003545:Cysteine