Modulation of major histocompatibility class II protein expression by varicella-zoster virus

We sought to investigate the effects of varicella-zoster virus (VZV) infect ion on gamma interferon (IFN-gamma)-stimulated expression of cell surface m ajor histocompatibility complex (MHC) class II molecules on human fibroblas ts, IFN-gamma treatment induced cell surface MHC class II expression on 60 to 86% of uninfected cells, compared to 20 to 30% of cells which had been i nfected with VZV prior to the addition of IFN-gamma. In contrast, cells tha t were treated with IFN-gamma before VZV infection had profiles of MWC clas s II expression similar to those of uninfected cell populations. Neither IF N-gamma treatment nor VZV infection affected the expression of transferrin receptor (CD71). In situ and Northern blot hybridization of MHC II (MHC cla ss II DR-alpha) RNA expression in response to IFN-gamma stimulation reveale d that MBC class II DR-alpha mRNA accumulated in uninfected cells but not i n cells infected with VZV. When skin biopsies of varicella lesions were ana lyzed by in situ hybridization, MHC class II transcripts were detected in a reas around lesions but not in cells that were infected with VZV. VZV infec tion inhibited the expression of Stat 1 alpha and Jak2 proteins but had lit tle effect on Jak1. Analysis of regulatory events in the IFN-gamma signalin g pathway showed that VZV infection inhibited transcription of interferon r egulatory factor 1 and the MHC class II transactivator. This is the first r eport that VZV encodes an immunomodulatory function which directly interfer es with the IFN-gamma signal transduction via the Jak/Stat pathway and enab les the virus to inhibit IFN-gamma induction of cell surface MHC class II e xpression. This inhibition of MRC class II expression on VZV-infected cells in vivo may transiently protect cells from CD4(+) T-cell immune surveillan ce, facilitating local virus replication and transmission during the first few days of cutaneous lesion formation.