Class I MHC molecule-mediated inhibition of Sindbis virus replication

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