DOWN-REGULATION OF VESICULAR STOMATITIS-VIRUS TRANSCRIPTION BY THE MATRIX PROTEIN OF INFLUENZA-VIRUS

The matrix (M1) protein isolated from influenza A/WSN/33 virus, when reconstituted with ribonucleoprotein (RNP) cores of vesicular stomatitis virus (VSV), resulted in inhibition of VSV transcription in vitro. The presence of endogenous wild-type (wt) or mutant (tsO23) VSV matrix (M) protein on RNP cores did not prevent down-regulation of VSV transcription by reconstituted influenza virus M1 protein. In fact, endogenous VSV wt M protein augmented transcription inhibition by M1 protein reconstituted with RNP/M protein cores, whereas mutant tsO23 M protein endogenous to RNP cores had no effect on down-regulation of VSV transcription by M1 protein. These data suggest that VSV M protein and influenza virus M1 protein recognize two different sites on RNP cores responsible for down-regulation of VSV transcription. Monoclonal antibodies (MAbs) directed to epitope 2 of M1 protein had been previously shown to reverse transcription inhibition by M1 protein on influenza virus RNP cores, but the same epitope 2-specific MAb had little effect on transcription inhibition by M1 protein reconstituted with VSV RNP cores. VSV M protein bears a striking resemblance biologically and genetically to the M1 protein, including, as shown here, their capacity to bind viral RNA. However, the VSV wt M protein exhibited no capacity to down-regulate transcription by influenza virus RNP cores. The significance of these studies is the identification on VSV RNP templates of at least two separate sites for recognition of protein factors that repress VSV transcription.