The patterns of accumulation of cellular RNAs in cells infected with a wild-type and a mutant herpes simplex virus 1 lacking the virion host shutoff gene

Brunella Taddeo, Audrey Esclatine, Bernard Roizman

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Cellular RNA extracted from quiescent human foreskin fibroblasts harvested at 1, 3, 7, or 12 h after infection was profiled on Affymetrix HG-U95Av2 arrays designed to detect 12,626 unique human transcripts. We also profiled RNA extracted from cells harvested at 1 and 7 h after infection with a mutant lacking the gene (ΔEL41) encoding a protein (vhs) brought into cells by the virus and responsible for nonselective degradation of RNA early in infection. We report the following: (t) of the 12 tested genes, up-regulated at least 3-fold relative to the values of mock infected cells, 9 were confirmed by real-time PCR. The microchip assays analyses indicate that there were 475 genes up-regulated ≥3-fold. The up-regulated genes were clustered into 15 groups with respect to temporal pattern of transcript accumulation, and classified into 20 groups on the basis of their function. The preponderance of cellular genes up-regulated early in infection play a predominant role in transcription, whereas those upregulated at later times respond to intracellular stress or concern themselves with the cell cycle and apoptosis. (ii) The number of genes up-regulated early in infection was higher in cells infected with the ΔUL41 mutant. Conversely, more genes were downregulated late in infection with wild-type virus than with mutant viruses. Both observations are compatible with the known function of the UL41 gene product early in infection and with degradation of cellular RNAs in the absence of replenishment by de novo transcription of cellular genes.

Original languageEnglish
Pages (from-to)17031-17036
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number26
DOIs
StatePublished - 24 Dec 2002

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