Studies of adenovirus-SV40 hybrid viruses, VI. Differential effects of interferon on SV40 and adenovirus T antigen formation in cells infected with SV40 virus, adenoviruses, and adenovirus-SV40 hybrid viruses.

Abstract

Both genetic and biophysical studies have indicated linkage between adenovirus and SV40 DNA in the adenovirus (Ad.) 7-SV40 virus E46+ (Ad. 7+).1-6 First, of the SV40 T antigen-inducing capacity from Ad. 7+ to other adenovirus types is regularly accompanied by the of a gene coding for an Ad. 7-specific T antigen.5 Second, by means of nucleic acid homology techniques, it was shown that the SV40 DNA in Ad. 7+ could not be separated from Ad. 7 DNA under conditions of centrifugation which readily separated the two nonhybrid DNA's when present in an artificial mixture. Since the same result was obtained after alkali denaturation of the Ad. 7+ DNA, it was concluded that the DNA's of the virus particles are covalently linked.6 Thus, the adenovirus-SV40 hybrids may offer a unique opportunity to study the effects of linkage on the function of these unrelated viral genes. One potentially useful tool for the study of the expression of viral genetic function is interferon. The antiviral action of interferon appears to be mediated by an induced intracellular protein that blocks the translation of viral, but inot host cell, messenger RNA (mRNA).7-11 It has been demonstrated previously that T antigen formation by SV40 is sensitive to interferon in a nonlytic system (the 3T3 mouse cell line),12 and more recent findings (reported here) have indicated that SV40 is initerferon-sensitive in monkey and human cells as well. In contrast, we have found the formation of adenovirus T antigens to be relatively resistant to interferon. Therefore, we have compared the interferon sensitivity of adenovirus and SV40 T antigen formation in cells infected with the adenovirus-SV40 viruses, SV40 virus, nonhybrid adenoviruses, and mixtures of SV40 and nonhybrid adenoviruses. In addition to Ad. 7+ other strains were used-the transfer hybrids, which contain the genetic material of Ad. 7+ in capsids of heterologous adenovirus types,5' 13 and a type of hybrid which yields infectious SV40 virus. 14 The studies reported here provide evidence for an interaction between the adellovirus and SV40 genes in hybrid-infected cells, but not in cells coinfected by SV40 and nonhybrid adenoviruses.