VESICULAR STOMATITIS-VIRUS MESSENGER-RNA AND INHIBITION OF TRANSLATION OF CELLULAR MESSENGER-RNA MESSENGER-RNA - IS THERE A P FUNCTION IN VESICULAR STOMATITIS-VIRUS

Infection of animal cells by vesicular stomatitis virus (VSV) results in inhibition of translation of cellular mRNA. In BHK (baby hamster kidney) cells infected by the Glasgow isolate of VSV Indiana, this is due to competition during the initiation step of protein synthesis of viral and cellular mRNA for a constant, limiting number of ribosomes. Infection of the same cells with the San Juan isolate of VSV resulted in a more rapid shutoff of host protein synthesis and this was paralleled by a more rapid accumulation of viral mRNA. Extending the conclusion that shutoff is due to mRNA competition, it is shown that the average size of polysomes translating viral and cellular mRNA was 3-fold smaller in cells infected by VSV San Juan than by VSV Glasgow, which, in turn, was .apprx. 1/2 that of uninfected cells. In all cases, cellular and viral mRNA which encoded the same-sized polypeptides were found on the same-sized polysomes, a result indicating that the efficiency of translation of both types of mRNA is about the same in the infected cell. Also, there was no preferential sequestration of viral or cellular mRNA in ribonucleoprotein particles. Additional correlations between the levels of viral mRNA and the inhibition of protein synthesis came from studies of 3 other wild-type VSV strains and also from studies with Vero [African green monkey kidney] and L [mouse fibroblast] cells. The rate of shutoff of L cell protein synthesis after infection by any VSV isolate was slower than that in BHK cells and this was correlated with a slower rate of accumulation of viral mRNA. VSV temperature-sensitive mutants which synthesized, at the nonpermissive temperature, no VSV mRNA failed to inhibit synthesis of cellular proteins. Stanners et al. claimed that VSV mutant R1 inhibited synthesis of L cell protein synthesis less rapidly than did its parent wild-type strain HR and that this effect was due to a mutation in an unspecified VSV protein, P. In L and BHK cells, R1 infection resulted in a slightly slower inhibition of cellular mRNA translation than did HR infection and this was correlated with a slightly reduced accumulation of VSV mRNA. The level of VSV mRNA, rather than any specific VSV protein, appeared to be the key factor in determining the rate of shutoff of host protein synthesis.