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Although parainfluenza virus 5 (simian virus 5 [SV5]) circumvents the interferon (IFN) response by blocking IFN signaling and by reducing the amount of IFN released by infected cells, its ability to circumvent the IFN response is not absolute. The effects of IFN on SV5 infection were examined in Vero cells, which do not produce but can respond to IFN, using a strain of SV5 (CPI-) which does not block IFN signaling. Thus, by infecting Vero cells with CPI- and subsequently treating the cells with exogenous IFN, it was possible to observe the effects that IFN had on SV5 infection in the absence of virus countermeasures. IFN rapidly (within 6 h) induced alterations in the relative levels of virus mRNA and protein synthesis and caused a redistribution of virus proteins within infected cells that led to the enhanced formation of virus cytoplasmic inclusion bodies. IFN induced a steeper gradient of mRNA transcription from the 3' to the 5' end of the genome and the production of virus mRNAs with longer poly(A) tails, suggesting that the processivity of the virus polymerase was altered in cells in an IFN-induced antiviral state. Additional evidence is presented which suggests that these findings also apply to the replication of strains of SV5, parainfluenza virus type 2, and mumps virus that block IFN signaling when they infect cells that are already in an IFN-induced antiviral state.

Some of the human prostatic cells in culture apparently produce oncornavirus-like particles. Bromodeoxyuridine does not enhance the production of these particles. On the contrary, this drug depresses such production. This depression is likely to be due to the cytotoxic effects of bromodeoxyuridine for these cells. These results can be interpreted to suggest that the human prostatic cells used in this study do not contain endogenous oncornavirus genetic information that is inducible. Purified human interferon inhibits the production of oncornavirus-like particles by these prostatic cells. It is also inhibits the rate of cellular DNA synthesis in these cells. These results are consistent with the notion that the inhibitory effects of interferon are mediated through its effect on cellular biosynthetic machinery.

Several factors affected the interferon sensitivity of human cytomegalovirus in human foreskin fibroblast cultures. An inoculum of infected cells was up to 300-fold less sensitive than a cell-free inoculum of equivalent input multiplicity. A 10-fold increase in the dose of infectious units of either type of inoculum was associated with a 10-fold or greater decrease in interferon sensitivity. Several aspects of the virus-cell interaction were examined and parameters indicative of cell infection were less inhibited by interferon than were those for virus replication.

X-ray transformed mouse C3H/10T1/2 cells were cultivated and passaged in the continuous presence of partially purified mouse interferon. This prolonged interferon treatment resulted in a stepwise progressive reversion of the transformed phenotype to the non-transformed phenotype. Thus interferon-treated cells displayed an epithelioid morphology, grew to a lower cell density, and were no longer tumorigenic. Reversion to the non-transformed phenotype was, however, stable only as long as interferon was continuously present in the culture medium. When interferon was removed, the cells "back reverted" to the transformed phenotype. Our results suggest that interferon induced a reversion of the transformed phenotype in the entire cell population rather than a selection of an interferon resistant cell population. C-type viral particles and significant levels of reverse transcriptase were present in transformed cells, but neither present in the parental 10T1/2 cells nor in interferon-treated cells. When interferon was removed form the culture medium, viral particles and reverse transcriptase activity were again detected. It is possible, therefore, that interferon induces reversion through its antiviral activity, or that it induces reversion by its effects on cell function and structure, independently of any antiviral effect. Inhibition of cell multiplication per se does no appear to be sufficient to induce reversion, since cycloheximide inhibited cell multiplication; however, even after ten passages, it did not affect tumorigenicity. Our results suggest the possibility that interferon may act in vivo not only by inhibiting tumor cell multiplication but also by inducing a reversion. Patients with some tumors may therefore benefit from long-term interferon treatment.