Herpes simplex virus type 1 suppresses the interferon signaling pathway byinhibiting phosphorylation of STATs and janus kinases during an early infection stage

We examined the influence on the interferon (IFN) signaling pathway of infe ction with herpes simplex virus type 1 (HSV-1 strain VR3. Data from reporte r gene assays showed that expression of both type I and type II IFN-inducib le genes was dramatically suppressed during the early stage of HSV-1 infect ion (2 to 3 h postinfection). During these periods, phosphorylation levels of janus kinases (JAKs) and STATs did not increase after treatment of HSV-1 -infected FL cells with IFN-alpha or IFN-gamma, although cellular protein l evels of the JAKs and the sTATs were not significantly changed. In contrast , the inhibitory effect of HSV-1 on phosphorylation of STAT1 was not observ ed in U937 cells, which show resistance to steady-state accumulation of RNA for HSV-1 immediate-early genes. The phosphorylation of STAT1 in FL cells was not inhibited by infection with a UV-inactivated virus. These results i ndicate that Viral gene expression or viral protein production is necessary for the inhibition of phosphorylation by HSV-1. (C) 2001 Academic Press.