Naslov
A viral protein reveals a biological role for stat2 in IFNg receptor signaling

Autori
Hengel, Hartmut ; Zimmermann, Albert ; Wilborn, Manuel ; Wagner, Marcus ; Ziade, Toufic ; Bubic, Ivan ; Triling, Mirko ; Jonjić, Stipan ; Koszinowski, Ulrich ;

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, pregledni

Izvornik
28th International Herpesvirus Workshop / Compton, Teresa ; Sugden, Bill ; - Madison (WI), 2003

Skup
28th International Herpesvirus Workshop

Mjesto i datum
Madison (WI), Sjedinjene Američke Države, 26.07.2003. - 31.07.2003

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
stat2; signaling

Sažetak
Cytomegaloviruses (CMVs) inhibit type I and type II interferon (IFN) receptor signaling through the JAK/STAT pathway and IFN-dependent expression of antiviral target genes. Based on a forward genetic procedure involving screening of a library of CMV mutants derived from random transposon mutagenesis by cis-acting reporter genes we identified the gene m27 of mouse CMV (MCMV) to mediate this effect. Expression of m27 prevented nuclear accumulation of STAT2 in infected cells and resulted in a rapid proteasome-dependent degradation of STAT2 but not STAT1. Isolated expression of m27 was sufficient to mediate these effects. Deletion of m27 conferred susceptibility of MCMV replication to IFN-a/b. Unexpectedly, m27 had a much more drastic effect on IFN-g mediated antiviral activities which was strictly dependent on STAT2 and was also contingent on IFN-a/bR1 expression. Replication of the m27MCMV mutant was dramatically attenuated in wildtype mice but partly restored in IFN-a/bR-deficient as well as IFN-gR-deficient mice. The results establish a new mechanism for viral immune escape and document an unforeseen biological significance of STAT2 in IFN-gR signaling. The data support a model of molecular cross-talk between IFN-g and IFN-a/b signaling components which requires STAT2.

Izvorni jezik
Engleski

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