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PMID: 12133999 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Bunyamwera bunyavirus nonstructural protein NSs counteracts the induction of alpha/beta interferon.

Journal of virology ·Vol. 76 ·No. 16 ·2002-08-00 ·Pages 7949-55

Weber F, Bridgen A, Fazakerley JK, Streitenfeld H, Kessler N, Randall RE, Elliott RM

Abstract

Production of alpha/beta interferons (IFN-alpha/beta) in response to viral infection is one of the main defense mechanisms of the innate immune system. Many viruses therefore encode factors that subvert the IFN system to enhance their virulence. Bunyamwera virus (BUN) is the prototype of the Bunyaviridae family. By using reverse genetics, we previously produced a recombinant virus lacking the nonstructural protein NSs (BUNdelNSs) and showed that NSs is a nonessential gene product that contributes to viral pathogenesis. Here we demonstrate that BUNdelNSs is a strong inducer of IFN-alpha/beta, whereas in cells infected with the wild-type counterpart expressing NSs (wild-type BUN), neither IFN nor IFN mRNA could be detected. IFN induction by BUNdelNSs correlated with activation of NF-kappaB and was dependent on virally produced double-stranded RNA and on the IFN transcription factor IRF-3. Furthermore, both in cultured cells and in mice lacking a functional IFN-alpha/beta system, BUNdelNSs replicated to wild-type BUN levels, whereas in IFN-competent systems, wild-type BUN grew more efficiently. These results suggest that BUN NSs is an IFN induction antagonist that blocks the transcriptional activation of IFN-alpha/beta in order to increase the virulence of Bunyamwera virus.

MeSH Terms
Animals Bunyamwera virus/genetics,immunology,pathogenicity,physiology Bunyaviridae Infections/genetics,immunology,metabolism Cells, Cultured Chlorocebus aethiops DNA-Binding Proteins/metabolism Female Gene Deletion Genes, Viral Humans Interferon Regulatory Factor-3 Interferon-alpha/biosynthesis,genetics Interferon-beta/biosynthesis,genetics Membrane Proteins Mice Mice, Knockout NF-kappa B/metabolism Promoter Regions, Genetic RNA, Double-Stranded/genetics,metabolism RNA, Messenger/genetics,metabolism Receptor, Interferon alpha-beta Receptors, Interferon/deficiency,genetics Transcription Factors/metabolism Transcriptional Activation Vero Cells Viral Nonstructural Proteins/genetics,immunology Virulence Virus Replication
Chemicals
DNA-Binding Proteins IRF3 protein, human Interferon Regulatory Factor-3 Interferon-alpha Irf3 protein, mouse Membrane Proteins NF-kappa B NSs protein, Bunyamwera bunyavirus RNA, Double-Stranded RNA, Messenger Receptors, Interferon Transcription Factors Viral Nonstructural Proteins Receptor, Interferon alpha-beta Interferon-beta
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Weber Friedemann
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Germany.
Bridgen Anne
Fazakerley John K
Streitenfeld Hein
Kessler Nina
Randall Richard E
Elliott Richard M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.16.7949-7955.2002
Published
2002-08-00
Pages
7949-55
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC155133
Subset
IM
External Links
PubMed source DOI: 10.1128/jvi.76.16.7949-7955.2002 PMC Full Text View journal details
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