Earlier we reported a reduction to 1/30th-1/100th of the original number of infectious particles in the infectious vesicular stomatitis virus (VSV) released from L cells treated with 10 or 30 reference units of interferon per ml. However, in these cultures virus particle production, as measured by VSV particle-associated viral RNA, virus nucleocapsid protein, and viral transcriptase, was inhibited by less than 10%. Data reported in this paper show that there was a significant reduction in glycoprotein and membrane protein of VSV particles released from interferon-treated cells. Evidence supporting the deficiency of glycoprotein in VSV released from interferon-treated cells was derived from electron microscopic studies. Under conditions where glycoprotein spikes or projections were clearly detectable on the surface of VSV released from cells not treated with interferon, very few spikes were observed on VSV released from interferon-treated cells. These results suggested that interferon-treated cells produced VSV particles with low infectivity and that this low infectivity may be related to the reduced amount of glycoprotein and membrane protein incorporated into such particles. Interferon inhibits the replication of a wide variety of viruses. In most systems studied, virus-directed translation or transcription was inhibited (1); however, an unusual inhibitory effect of interferon treatment on the replication of RNA tumor viruses has been reported. Inhibition of RNA tumor virus production was not correlated with inhibition of any of the intracellular steps in virus replication that were tested (2-6). Inhibition of virus production was not correlated with inhibition of the accumulation of viral RNA (7) or of viral proteins (8). In interferon-treated AKR cells there was decreased production of both endogenous murine leukemia virus (MLV) particles and infectious MLV; however, the intracellular concentration of viral p30 antigen was increased (8). Studies on the action of interferon in Moloney MLV infection of mouse bone marrow/thymus (TB) cells showed that in interferon-treated cells there was a decrease in the production of infectious MLV to 1/2000th the original number, a decrease in the level of virus-specific reverse transcriptase activity to 1/lOth-1/20th the original activity, and only a 2-fold difference in the number of budding viral particles observed on the plasma membrane as determined by scanning electron microscopy studies (9). These results suggested that in these systems, either the release of virus from the plasma membrane or the production of infectious virus particles was inhibited by treatment with interferon.One important question about this work is whether such findings are restricted to RNA tumor virus systems. We have studied the effect of low concentrations of interferon (10 or 30 reference units/ml) on vesicular stomatitis virus (VSV) infection of L cells in contrast to previous studies, which used much higher interferon concentrations and reported inhibition of VSV-directed translatio...
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