VSV Functions that Affect Protein Synthesis Inhibition

Inhibitors of VSV Functions that Affect Protein Synthesis Inhibition 

A variety of chemical and physical agents have been used in an attempt to dissect and identify the VSV function(s) that inhibit cellular protein synthesis. 

Yamazaki and Wagner (1970) found that pretreatment of primary rabbit kidney cells with highly purified rabbit interferon greatly reduced VSV replication and inhibited synthesis of virus-specific proteins despite this inhibition of viral protein synthesis, interferon did not prevent the switch-off by VSV of cellular protein synthesis. This observation was interpreted, in retrospect erroneously, to be due to an input virion component rather than a newly synthesized viral product. It was originally thought that primary transcription of VSV is inhibited in interferon-treated cells (Marcus et al., 1971 Manders et al., 1972), but it now seems clear that only secondary transcription and not primary transcription is inhibited in interferon-pretreated cells (Repik et al., 1974). There is now quite convincing evidence that the interferon-induced inhibitor of VSV replication functions at the translational level (Sen, 1982). These circumstantial data point to the hypothesis that a VSV transcription product, alone or in association with another factor, is the inhibitor of cellular protein synthesis. 

Use of the general protein synthesis inhibitor, cycloheximide, led to the hypothesis that de novo VSV protein synthesis is required for inhibiting cellular protein synthesis because, when cycloheximide was removed from infected cells, viral protein synthesis preceded suppression of cellular protein synthesis inhibition (Wertz and Young-ner, 1972). In our experience, experiments such as these are difficult to interpret because cycloheximide has many side effects, such as inhibition of cellular RNA synthesis (Week and Wagner, unpublished data). 

RNA and N gene mRNA in tightly controlled cell-free translation systems. 

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