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PMID: 16501120 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibition of interferon signaling by the Kaposi's sarcoma-associated herpesvirus full-length viral interferon regulatory factor 2 protein.

Journal of virology ·Vol. 80 ·No. 6 ·2006-03-00 ·Pages 3092-7

Fuld S, Cunningham C, Klucher K, Davison AJ, Blackbourn DJ

Abstract

Interferon (IFN) signal transduction involves interferon regulatory factors (IRF). Kaposi's sarcoma-associated herpesvirus (KSHV) encodes four IRF homologues: viral IRF 1 (vIRF-1) to vIRF-4. Previous functional studies revealed that the first exon of vIRF-2 inhibited alpha/beta interferon (IFN-alpha/beta) signaling. We now show that full-length vIRF-2 protein, translated from two spliced exons, inhibited both IFN-alpha- and IFN-lambda-driven transactivation of a reporter promoter containing the interferon stimulated response element (ISRE). Transactivation of the ISRE promoter by IRF-1 was negatively regulated by vIRF-2 protein as well. Transactivation of a full-length IFN-beta reporter promoter by either IRF-3 or IRF-1, but not IRF-7, was also inhibited by vIRF-2 protein. Thus, vIRF-2 protein is an interferon induction antagonist that acts pleiotropically, presumably facilitating KSHV infection and dissemination in vivo.

MeSH Terms
Cell Line Herpesvirus 8, Human/genetics,metabolism,pathogenicity Humans Interferon Regulatory Factor-2/genetics,metabolism,pharmacology Interferon-alpha/antagonists & inhibitors,metabolism Interferon-beta/antagonists & inhibitors,metabolism Interferon-gamma/antagonists & inhibitors,metabolism Interferons/antagonists & inhibitors,metabolism Promoter Regions, Genetic Signal Transduction Transfection Viral Proteins/genetics,metabolism,pharmacology
Chemicals
Interferon Regulatory Factor-2 Interferon-alpha Viral Proteins Interferon-beta Interferon-gamma Interferons
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Fuld Suzanne
Lab22 Limited, Unit 184, The Science Park, Cambridge, United Kingdom.
Cunningham Charles
Klucher Kevin
Davison Andrew J
Blackbourn David J
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.80.6.3092-3097.2006
Published
2006-03-00
Pages
3092-7
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1395420
Subset
IM
Grants
Medical Research Council · MC_U130184136 · United Kingdom
Medical Research Council · MC_UU_12014/3 · United Kingdom
Wellcome Trust · 059008/Z/99/Z · United Kingdom
External Links
PubMed source DOI: 10.1128/JVI.80.6.3092-3097.2006 PMC Full Text View journal details
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