Herpes simplex virus-induced changes in cellular and adenovirus RNA metabolism in an adenovirus type 5-transformed human cell line

Abstract

We used the viral transcripts (designated Ad-RNA) that accumulated in the cytoplasm of adenovirus type 5-transformed human embryonic kidney cells (cell line 293-31) as models for cellular RNAs to examine how herpes simplex virus modifies cellular RNA metabolism. Infection of 293-31 cells with herpes simplex virus type 1 strain 17 led to extensive inhibition of Ad-RNA accumulation by 4 h postinfection. The major part of this inhibition was due to an immediate early or alpha gene function, which reduced the rate of transcription of Ad-RNA within the nuclei of the infected cells. In addition, host polyadenylic acid-containing RNA accumulation and rRNA accumulation were affected, but to a lesser extent and at a slower rate than Ad-RNA accumulation. In conjunction with previous data, our experimental data allowed us to propose a general scheme for how herpes simplex virus type 1 alters the metabolism of cellular RNA, the possible mechanisms for these changes, and how they correlate with the regulation of herpes simplex virus gene expression.

Repression of host RNA polymerase II transcription by herpes simplex virus type 1

“…Our observation that repression of host gene transcription depends upon IE gene expression is in agreement with the results of an earlier study that examined the effects of HSV-1 infection on transcription of adenovirus-specific RNAs in a cell line transformed by adenovirus (52). Adenovirus-specific transcription is inhibited by 75% after infection of cells with either wild-type HSV-1 or an ICP4 mutant virus.…”

“…Transcription of adenovirus RNA in cells transformed by adenovirus type 5 is inhibited by more than 70% following infection with HSV. This inhibition of adenovirus transcription requires expression of HSV IE genes (52). Similarly, polyomavirus-specific RNA synthesis declines to less than 10% of uninfected levels when polyomavirus-transformed cells are infected with HSV (34).…”

Herpes simplex virus types 1 and 2 induce shutoff of host protein synthesis by different mechanisms in Friend erythroleukemia cells

“…Wagner and Roizman (37) have shown that HSV-1 disrupts the synthesis and processing of cellular rRNA. HSV-1 has also been shown to inhibit the synthesis and accumulation of adenovirus-specific polyadenylated RNAs in adenovirus-transformed cell lines (31,32). Nishioka and Silverstein (17,19) provided evidence that HSV-1 produces an immediate early viral function which degrades cellular mRNA, and Stenberg and Pizer (32) also identified an HSV-1 function which degrades adenovius-specific transcripts in HSV-1-infected, adenovirus-transformed cells.…”

“…Shortly after infection with either HSV-1 or HSV-2, cellular polysomes disaggregate (10,19,34,35), and host protein synthesis begins an irreversible decline (10,18,23,34). In addition, HSV-1 causes the dissociation of cellular mRNA from the polysomes (19), degrades host RNA (17,19,32), inhibits the synthesis of cellular DNA (24) and RNA (32), and reduces glycosylation of cellular proteins (30).…”

Regulation of Protein Synthesis in Virus-Infected Animal Cells

“…Herpes simpler: (1) Pereira et al (1977). (2) Fenwick and Walker (1978); Stenberg and Pizer (1982). (3) Stage 1-see text; stage 2- Inglis (1982); Nishioka and Silverstein (1978b).…”