Human parainfluenza virus type 3 inhibits gamma interferon-induced major histocompatibility complex class II expression directly and by inducing alpha/beta interferon

Human parainfluenza virus type 3 (HPIV3) is one of the major causes of bron chiolitis, pneumonia, and croup in newborns and infants. Cellular immunity involving major histocompatibility complex (MHC) class I and class II molec ules plays an important role in controlling virus infection. Several viruse s have been shown to down-regulate gamma interferon (IFN-gamma)-mediated MH C class II expression. In this communication, we show that HPIV3 strongly i nhibits the IFN-gamma -induced MHC class II expression in HT1080 human fibr osarcoma cells. The culture supernatant of HPIV3-infected cells also inhibi ted IFN-gamma -induced MHC class II expression, a phenomenon that was found to be due, in large part, to alpha/beta interferon (IFN-alpha/beta). Expre ssion of MHC class I and intercellular adhesion molecule 1 occurred efficie ntly in cells simultaneously infected with HPIV3 and treated with IFN-gamma , indicating that the inhibitory effect of HPIV3 was specific to MHC class II, STAT1 activation was not affected by HPIV3 at early postinfection times but was partially inhibited at later times. These data suggested that the potent Inhibition of MHC class II expression was, in major part, due to a d efect downstream of STAT1 activation in the IFN-gamma -induced MHC class II expression pathway. Class II transactivator (CIITA) is the unique mediator of IFN-gamma -induced transcription from the MHC class II promoter, By RNa se protection analysis, CIITA expression was found to be strongly inhibited in HPIV3-infected cells. The culture supernatant containing IFNII-alpha/be ta, on the other hand, inhibited MHC class II expression without affecting STAT1 and CIITA expression. These data indicate that HPIV3 inhibits IFN-gam ma -induced MHC class II expression primarily by the viral gene products ta rgeting CIITA and additionally by inducing IFN-alpha/beta to target one or more steps further downstream.