Figure 2.
Gammaherpesviruses inhibit MHC-II-restricted antigen presentation. SOCS3 expression is upregulated by KSHV infection, which inhibits IFN-γ-induced phosphorylation of STAT1, thereby downregulating the transactivation of CIITA gene. BZLF1 and vIRF3 bind to the promoters of CIITA genes and thus interfere with its transactivation. BZLF1 reduces IFN-γR α expression at both the mRNA and protein level, and in that way shuts down the entire IFN-γ-induced CIITA signaling cascade. gp42 blocks TCR and MHC-II engagement. vIL-10 reduces IFN-γ synthesis and inhibits both basal and IFN-γ-induced expressions of MHC-II.