Involvement of herpes simplex virus type 1 UL13 protein kinase in the induction of SOCS genes, the negative regulator of cytokine signaling

The suppressor of cytokine signaling (SOCS) family consists of 8 members and suppresses various cytokine signaling pathways including interferon (IFN) signaling. Therefore, some viruses have evolved molecular mechanisms to induce SOCS proteins in order to escape from host immunity. Herpes simplex virus type 1 (HSV-1) has a mechanism for escaping from type I IFN by induction of SOCS1 and SOCS3 as well. In this study, expression of 8 members of the SOCS family by HSV-1 infection was comparatively analyzed by quantitative reverse transcription PCR. The result showed that SOCS1 and SOCS3 were induced by HSV-1-infection at 4 h post infection. However, this induction was not observed in UL13 deficient virus-infected cells, therefore, UL13 protein kinase was thought to participate in the induction of both genes. The transcription factor Sp1-binding sites of SOCS3 promoter/enhancer region were identified as the regulatory elements for the induction of SOCS3 in HSV-1 infected cells. The accumulation of activated Sp1 was actually detectable in the nuclei of HSV-1-infected cells before induction of SOCS3. Taken together, these results suggest that HSV-1 has a potent mechanism for escaping from the IFN system.