Synthesis and metabolism of cellular transcripts in HSV-1 infected cells

Abstract

The effects of productive herpes simplex virus infection on host gene expression were examined by measuring the rates of synthesis and subsequent fates of several Vero cell mRNAs. The rates of transcription of actin, beta-tubulin, and histone-3 and -4 RNAs were measured by pulse-labeling of intact cells as well as by run-on transcription in isolated nuclei. At both early (2 hr) and late (6 hr) times, the relative rates of transcription of these RNAs were greater than in uninfected cells. Kinetic labeling experiments performed at late times also revealed increased turnover rates of nuclear RNAs. That the rate of appearance of these RNAs in the cytoplasm was also reduced suggests that these cellular RNAs are being specifically retained and degraded in the nucleus. Levels of pre-existing cytoplasmic RNAs as measured by Northern blot analysis declined rapidly after infection though the nuclear steady-state levels of these RNAs increased up to 3 hr postinfection and then declined between 3 and 10 hr postinfection. At no time was the accumulation of processing intermediates detectable. Finally, we also determined that, consistent with the decline in levels of histone mRNA, rates of histone protein synthesis declined rapidly after infection.