Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins

Wen Jun Liu, Xiang Ju Wang, Vladislav V. Mokhonov, Pei-Yong Shi, Richard Randall, Alexander A. Khromykh

Research output: Contribution to journalArticle

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Abstract

The interferon (IFN) response is the first line of defense against viral infections, and the majority of viruses have developed different strategies to counteract IFN responses in order to ensure their survival in an infected host. In this study, the abilities to inhibit IFN signaling of two closely related West Nile viruses, the New York 99 strain (NY99) and Kunjin virus (KUN), strain MRM61C, were analyzed using reporter plasmid assays, as well as immunofluorescence and Western blot analyses. We have demonstrated that infections with both NY99 and KUN, as well as transient or stable transfections with their replicon RNAs, inhibited the signaling of both alpha/beta IFN (IFN-α/β) and gamma IFN (IFN-γ) by blocking the phosphorylation of STAT1 and its translocation to the nucleus. In addition, the phosphorylation of STAT2 and its translocation to the nucleus were also blocked by KUN, NY99, and their replicons in response to treatment with IFN-α. IFN-α signaling and STAT2 translocation to the nucleus was inhibited when the KUN nonstructural proteins NS2A, NS2B, NS3, NS4A, and NS4B, but not NS1 and NS5, were expressed individually from the pcDNA3 vector. The results clearly demonstrate that both NY99 and KUN inhibit IFN signaling by preventing STAT1 and STAT2 phosphorylation and identify nonstructural proteins responsible for this inhibition.

Original languageEnglish (US)
Pages (from-to)1934-1942
Number of pages9
JournalJournal of Virology
Volume79
Issue number3
DOIs
StatePublished - Feb 2005
Externally publishedYes

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West Nile virus
interferons
Interferons
Proteins
proteins
Replicon
replicon
Phosphorylation
phosphorylation
Interferon-gamma
interferon-beta
Interferon-beta
Virus Diseases
Interferon-alpha
transfection
Fluorescent Antibody Technique
Transfection
interferon-gamma
infection
fluorescent antibody technique

ASJC Scopus subject areas

  • Immunology

Cite this

Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins. / Liu, Wen Jun; Wang, Xiang Ju; Mokhonov, Vladislav V.; Shi, Pei-Yong; Randall, Richard; Khromykh, Alexander A.

In: Journal of Virology, Vol. 79, No. 3, 02.2005, p. 1934-1942.

Research output: Contribution to journalArticle

Liu, Wen Jun ; Wang, Xiang Ju ; Mokhonov, Vladislav V. ; Shi, Pei-Yong ; Randall, Richard ; Khromykh, Alexander A. / Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins. In: Journal of Virology. 2005 ; Vol. 79, No. 3. pp. 1934-1942.
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