Journalartikel

Bunyamwera Virus Nonstructural Protein NSs Counteracts Interferon Regulatory Factor 3-Mediated Induction of Early Cell Death


AutorenlisteKohl, A; Clayton, RF; Weber, F; Bridgen, A; Randall, RE; Elliott, RM

Jahr der Veröffentlichung2003

Seiten7999-8008

ZeitschriftJournal of Virology

Bandnummer77

Heftnummer14

ISSN0022-538X

DOI Linkhttps://doi.org/10.1128/JVI.77.14.7999-8008.2003

VerlagAmerican Society for Microbiology


Abstract
The genome of Bunyamwera virus (BUN; family Bunyaviridae, genus Orthobunyavirus) consists of three segments of negative-sense RNA. The smallest segment, S, encodes two proteins, the nonstructural protein NSs, which is nonessential for viral replication and transcription, and the nucleocapsid protein N. Although a precise role in the replication cycle has yet to be attributed to NSs, it has been shown that NSs inhibits the induction of alpha/beta interferon, suggesting that it plays a part in counteracting the host antiviral defense. A defense mechanism to limit viral spread is programmed cell death by apoptosis. Here we show that a recombinant BUN that does not express NSs (BUNdeINSs) induces apoptotic cell death more rapidly than wild-type virus. Screening for apoptosis pathways revealed that the proapoptotic transcription factor interferon regulatory factor 3 (IRF-3) was activated by both wild-type BUN and BUNdeINSs infection, but only wild-type BUN was able to suppress signaling downstream of IRF-3. Studies with a BUN minireplicon system showed that active replication induced an IRF-3-dependent promoter, which was suppressed by the NSs protein. In a cell line (P2.1) defective in double-stranded RNA signaling due to low levels of IRF-3, induction of apoptosis was similar for wild-type BUN and BUNdeINSs. These data suggest that the BUN NSs protein can delay cell death in the early stages of BUN infection by inhibiting IRF-3-mediated apoptosis.



Zitierstile

Harvard-ZitierstilKohl, A., Clayton, R., Weber, F., Bridgen, A., Randall, R. and Elliott, R. (2003) Bunyamwera Virus Nonstructural Protein NSs Counteracts Interferon Regulatory Factor 3-Mediated Induction of Early Cell Death, Journal of Virology, 77(14), pp. 7999-8008. https://doi.org/10.1128/JVI.77.14.7999-8008.2003

APA-ZitierstilKohl, A., Clayton, R., Weber, F., Bridgen, A., Randall, R., & Elliott, R. (2003). Bunyamwera Virus Nonstructural Protein NSs Counteracts Interferon Regulatory Factor 3-Mediated Induction of Early Cell Death. Journal of Virology. 77(14), 7999-8008. https://doi.org/10.1128/JVI.77.14.7999-8008.2003


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