Inhibition of SV40 T antigen formation by interferon.

Abstract

Pretreatment of mouse fibroblast (3T3) cells with interferon reduced the number of cells that produced SV40 T antigen after infection with SV40 virus and resulted in a delay of T antigen formation in ultimately positive cells. This sensitivity to interferon was lost by 4 hr. after viral infection. Transformation of 3T3 cells by SV40 was as sensitive to the inhibitory action of interferon as T antigen formation, suggesting that interferon inhibits a single function necessary for both of these expressions of the SV40 viral genome. The results indicate that interferon acts by inhibiting an early function of the input viral DNA. The SV40 T antigen was found to be stable in nondividlng and transformed cells, but was lost with division in nontransformed cells. The hypothesis was advanced that 2 alternative virus-cell associations may exist in SV40-lnfected 3T3 cells, with the SV40 genome coding for T antigen in both. In one case the viral genome is 2integrated and interferon-resistant, resulting in transformation and perpetuation of T antigen formation through succeeding generations. In the other, the SV40 genome is not integrated and remains interfer on-sensitive; transformation does not occur and T antigen formation is lost with cell division.