Herpes simplex virus type 1 infection leads to loss of serine-2 phosphorylation on the carboxyl-terminal domain of RNA polymerase II

Kathryn A Fraser, Stephen A Rice

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22 Scopus citations

Abstract

Previous studies have shown that herpes simplex virus type 1 (HSV-1) infection alters the phosphorylation of the carboxyl-terminal domain (CTD) of RNA polymerase II (RNAP II), creating a new form of the enzyme known as RNAP III. However, the specific phosphorylation changes induced by HSV-1 have not been characterized. In this study, we used phospho-specific anti-CTD antibodies to probe the structure of the postinfection RNAP II. We find that RNAP III is phosphorylated on serine-5 (Ser-5) of the CTD consensus repeat but generally lacks phosphorylation on serine-2 (Ser-2). Since Ser-2 phosphorylation is normally associated with efficient transcriptional elongation and the recruitment of pre-mRNA processing factors, our results suggest that RNAP III may have altered elongation properties and decreased interactions with the mRNA processing machinery. The viral factors responsible for the reduction in Ser-2 CTD phosphorylation were studied. We found that viral immediate-early (IE) gene expression is required and sufficient, in the context of infection, for loss of Ser-2 phosphorylation. However, studies with viral mutants failed to implicate a single IE protein (among ICP0, ICP4, ICP22, and ICP27) in this process. Although most Ser-2-phosphorylated RNAP II is lost after infection, our immunofluorescence analyses identified a small subfraction that escapes loss and relocalizes to splicing antigen-rich nuclear speckles. A similar phenomenon is seen in uninfected cells after various treatments that inhibit RNAP II transcription. We hypothesize that the HSV-1-induced relocalization of residual Ser-2-phosphorylated RNAP II to nuclear speckles reflects a host response to the inhibition of cellular gene transcription.

Original languageEnglish (US)
Pages (from-to)11323-11334
Number of pages12
JournalJournal of virology
Volume79
Issue number17
DOIs
StatePublished - Sep 2005

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