Class I MHC molecule-mediated inhibition of Sindbis virus replication

The threshold for systemic viral infection relies on the amplification of v irus at a primary infection site. We have identified that class I MHC molec ules can trigger the inhibition of replication of Sindbis virus in a haplot ype- and allele-specific manner. Class I MHC molecules of H-2(d) haplotypes exhibit a strong inhibitory effect whereas H-2(k) haplotypes show minimal inhibition of Sindbis viral replication, By a single gene transfection of H -2(d) class I MHC molecules, into cells that express class I MHC molecules of H-2(k) haplotype and are susceptible to viral replication, these cells b ecame resistant to viral replication. The inhibition of viral replication b y class I MHC molecules occurs neither during the stage of virus entry/endo cytosis nor during virus maturation. Rather, viral-specific RNA replication , as well as viral gene expression, are inhibited in cells expressing inhib itory class I MHC molecules, This class I MHC molecule-mediated inhibition requires newly synthesized host gene products, implying the activation of a n intracellular signaling mechanism that is triggered by specific class I N MC molecules.