Control of Simian Virus 40 Gene Expression in Adenovirus-Simian Virus 40 Hybrid Viruses Synthesis of Hybrid Adenovirus 2-Simian Virus 40 RNA Molecules in Cells Infected with a Nondefective Adenovirus 2-Simian Virus 40 Hybrid Virus

Abstract

The effect of interferon on simian virus 40 (SV40) and adenovirus 2 (Ad2) T antigen synthesis has been examined in cells infected with SV40, with Ad2, and with a nondefective Ad2-SV40 hybrid virus, Ad2+ND4. The induction of SV40 T antigen by SV40 was highly sensitive to interferon, whereas the induction of Ad2 T-antigen by Ad2 was resistant. This difference in interferon sensitivity was also noted in cells simultaneously infected with both viruses. However, the induction of SV40 T antigen by Ad2+ND,, which contains covalently linked SV40 and Ad2 DNAs, was as resistant to interferon as the induction of Ad2 T antigen. This change in the interferon sensitivity of SV40 T antigen synthesis suggests that the expression of at least this portion of the SV40 genetic information in Ad2+ND4 is under Ad2 genetic control. When RNA extracted from Ad2+ND4-infected cells was examined by means of sequential hybridization with Ad2 DNA, elution, and rehybridization with SV40 DNA, 27% of the SV40-specific RNA was found to be linked to Ad2 RNA. No such linkage was detected in control mixtures of Ad2 and SV40 RNAs. The presence of Ad2 and SV40 nucleotide sequences in the same RNA molecule implies that, in Ad2+ND4 infection, transcription is initiated in the DNA of one virus (Ad2 or SV40) and continues without interruption across the point of junction into the DNA of the other virus. Furthermore, the interferon resistance of Ad2+ND4induced SV40 T antigen synthesis suggests that transcription of the genetic information for SV40 T antigen is initiated in a region of Ad2 DNA.

Antiviral activity of interferons.

“…There is strong independent evidence that the SV40 genome is covalently linked to the adenovirus genome in the hybrid (104) or to cellular DNA in SV40-transformed cells (115). The mRNA produced by the integrated SV40 genome contains host sequences (84), and the mRNA of the hybrid contains both adenovirus and SV40 sequences (104). The resistance of SV40 T-antigen production to interferon treatment in the case of integrated genomes may indicate that the primary sequence of nucleotides in the genome does not determine sensitivity to interferon.…”

Evidence for Simian Virus 40 (SV40) Coding of SV40 T-Antigen and the SV40-Specific Proteins in HeLa Cells Infected with Nondefective Adenovirus Type 2-SV40 Hybrid Viruses

“…The results of others suggest that there are covalently linked Ad2-SV40 RNA molecules in cells infected by Ad2+ND1 (3, 15), Ad2+ND3 (15), and Ad2+ND4 (3,46). Hybridization of cytoplasmic RNA to SV40 DNA-Sepharose will select for hybrid Ad2-SV40 RNA molecules as well as for RNA containing only SV40 sequences.…”

New chimeric splice junction in adenovirus type 2-simian virus 40 hybrid viral mRNA

“…From our pres-ent knowledge of SV40, it seems highly improbable that ND,, ND2, or ND4 contains an SV40 transciptional promoter (6,38). Consistent with this view is the finding that most, if not all, of the SV40-specific RNA molecules in nondefective hybrid virus-infected cells contain adenoviral sequences at the 5' end of the transcipts (13,16,36,44).…”