Interferon inhibits establishment of fibroblast infection with avian retroviruses.

Pretreatment of chick embryo fibroblasts (CEF) with low doses of homologous interferon (16 u/ml) drastically inhibits cell transformation by, and replication of Rous sarcoma virus (RSV). Treatment of chick cells with 16 u/ml of interferon before de novo infection with a transformation defective (td) mutant-RSV, also resulted in a reduction of extracellular virus particles. This was determined by infectivity titrations, virus associated reverse transcriptase (RT) activity and measurement of metabolically radioactively labelled virus particles. The viral proteins pr 180, pr 76, p 27, p 19 and p 12 were still synthesized in interferon-treated cells in an unaltered form, although at slightly reduced levels. No difference in the pattern of structural proteins could be detected between virus particles harvested from cells treated with interferon and from control cells. In contrast to de novo infected cells, concentrations of interferon as high as 200 u/ml had no influence on the reversible transformation of cloned fibroblasts infected with a temperature sensitive mutant of RSV. In addition, fibroblasts infected with td-SR-RSV-D before addition of interferon showed only a marginal effect on formation of infectious virus even after treatment with 200-500 u/ml of interferon. This was not caused by interferon-resistance of the td-SR-RSV-D infected cells since viral protein synthesis by superinfecting Vesicular stomatitis virus (VSV) was as sensitive to interferon as in cells not preinfected with retrovirus. Our results support the notion that exogenous infection of fibroblasts with avian retrovirus is inhibited by interferon during an early phase of the replication cycle.