Interferon Type I Downregulates Human Parainfluenza Virus Type 3-Induced Major Histocompatibility Complex Class II Expression

Abstract

Human parainfluenza virus type 3 (HPIV3) induces major histocompatibility complex (MHC) class II expression in a signal transducer and activator of transcription-1 (STAT1)- and class II transactivator (CIITA)-independent manner. Interferon (IFN)-γ, the potent inducer of MHC class II, on the other hand, requires both STAT1 and CIITA in the induction process. IFN-α/β has been shown to inhibit the IFN-γ-induced expression of MHC class II by targeting a step(s) downstream of CIITA. Here we report that IFN-α/β also inhibits the CIITA-independent expression of HPIV3-induced MHC class II. The inhibitory role of IFN-α/β on HPIV3-induced MHC class II was confirmed by using anti-IFN-α/β antibody and mutant cell lines defective in the IFN signaling components STAT1 and STAT2. IFN-α/β inhibits virus-induced MHC class II expression just as it does IFN-γ-induced MHC class II. The inhibition by IFN-α/β of MHC class II expression may play a regulatory role in virus induced autoimmune disease mediated by MHC class II aberrant expression.