Naslov
Novel Functions of Tyrosine Kinase 2 in the Antiviral Defence against Murine Cytomegalovirus

Autori
Strobl, Birgit ; Bubić, Ivan ; Bruns, Ute ; Steinborn, Ralf ; Lajko, Robert ; Kolbe, Thomas ; Karaghiosoff, Marina ; Kalinke, Ulrich ; Jonjić, Stipan ; Müller, Mathias

Izvornik
The Journal of Immunology (0022-1767) 175 (2005), 6; 4000-4008

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Tyk2; MCMV; IFN

Sažetak
We have recently reported that Tyk2-deficient mice have a selective defect in the in vivo defense against certain viruses. In our current study, we show that Tyk2 is essential for the defense against Murine Cytomegalovirus (MCMV). In vivo challenges with MCMV revealed impaired clearance of virus from organs and decreased survival of mice in the absence of Tyk2. Our in vitro studies demonstrate that MCMV replicates to dramatically higher titers in Tyk2-deficient macrophages as compared to wildtype cells. We show an essential role of type I interferon (IFN-ab) in the control of MCMV replication with a prominent role of IFN-b. MCMV infection leads to the activation of signal transducer and activator of transcription (STAT) 1 and 2 in an IFN-ab receptor 1 (IFNAR1) dependent manner. Consistent with the role of Tyk2 in IFN-ab signaling, activation of STAT1 and STAT2 is reduced in Tyk2-deficient cells. However, lack of Tyk2 results in impaired MCMV-mediated gene induction for a selective subset of MCMV-induced IFN-ab responsive genes. Taken together our data demonstrate a requirement for Tyk2 in the in vitro and in vivo antiviral defense against MCMV infection. In addition to the classical role of Tyk2 to amplify Jak/Stat signaling upon IFN-ab stimulation, we provide evidence for a novel role of Tyk2 for the modification of host responses.

Izvorni jezik
Engleski

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