Mechanism of Sindbis Virus-Induced Intrinsic Interference with Vesicular Stomatitis Virus Replication

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Abstract
Heterologous viral interference is induced by Sindbis virus against vesicular stomatitis virus (VSV) in a manner analogous to intrinsic interference with Newcastle disease virus replication. Interference in both systems (i) depends upon early expression of the inducing virus genome, (ii) shows similar kinetics of induction, (iii) does not involve interferon action, and (iv) appears to be manifest as an all-or-none effect. VSV can be added to the list of viruses blocked by intrinsic interference. Sindbis virus-induced intrinsic interference with VSV replication is not mediated through homotypic interference by defective interfering particles; rather, T-particle and B-particle synthesis is inhibited. Significantly, intrinsic interference has no effect on primary transcription directed by the virion-associated transcriptase in VSV-challenged cells. However, Sindbis virus appears to induce interference with the VSV-RNA synthesized subsequent to primary transcription, namely, that which is dependent on protein synthesis. Thus, the target of intrinsic interference appears to be a reaction subsequent to primary transcription but prior to the appearance of protein synthesis-dependent VSV RNA, secondary transcription.