The transcription and state of herpes simplex virus DNA in productive infection and in human cervical cancer tissue.

TLDR: The transcriptional program of herpes simplex viruses 1 and 2 in productive infection in human epidermoid cells and on the transcription and the stat e of HSV-2 DNA in a human cervical tumor suggest that the abundant RNA specifies structural proteins of the virus.

Abstract: Summary We are reporting on the transcriptional program of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) in productive infection in human epidermoid (HEp-2) cells and on the transcription and the stat eof HSV-2 DNA in a human cervical tumor. Our results may be summarized as follows. In productive infection, a total of 48% of HSV-1 DNA is transcribed. Analysis of the transcripts shows two kinds of controls. “Off-on” control of transcription is evident from the fact that early, before the onset of viral DNA synthesis, the transcripts arise from 44% of the DNA whereas late in infection the transcripts present in the infected cell arise from 48% of the DNA. The extent of transcription of the HSV-1 DNA early in infection is not affected by cycloheximide, an inhibitor of protein synthesis. Control of RNA abundance is evident from the observation that the transcripts present both early and late in infection form two classes differing in molar ratios. The abundant RNA is complementary to 14 and 19% of viral DNA early and late in infection, respectively, whereas the scarce RNA is complementary to 30 and 28%, respectively, of the DNA at the same time intervals. Several lines of evidence suggest that the abundant RNA specifies structural proteins of the virus. The transcriptional program of HSV-2 DNA differs from that of HSV-1 DNA in two respects. First, the amount of DNA transcribed early and late in infection corresponds to 21 and 50%, respectively. Second, while the viral RNA present late in infection also forms two classes differing in abundance, that present early in infection forms only one abundance class. Cycloheximide does affect transcription of HSV-2 DNA in that in the presence of the drug 45% of viral DNA is transcribed by 2 hr postinfection indicating that at least one “off-on” control of transcription is mediated by protein synthesis. HSV-1 and HSV-2 DNA9s share in common approximately 50% of their sequences with good matching of base pairs. Analysis of the transcription of the DNA sequences shared in common indicates that they are about evenly distributed among the templates for abundant and scarce RNA. However, the common sequences form 71% of the total sequences specifying abundant RNA and only 39% of the sequences specifying scarce RNA. A cervical tumor free of virus or viral antigen was analyzed by DNA-RNA hybridization techniques for the presence of viral RNA transcripts. The cervical tumor contained viral RNA transcripts complementary to 5% of HSV-2 DNA, and preliminary studies show that they correspond to both early and late transcripts. Analysis of the cervical DNA for the presence of HSV-2 DNA sequences led to three conclusions, i.e., first, only a fragment representing 40% of HSV-2 DNA was present; second, the fragment was present at concentrations of 1 mole/mole of cell DNA and, third, at least parts of this fragment are covalently linked to host DNA.