BioProject

Within the first 15 minutes of infection, herpes simplex virus 1 (HSV-1) immediate early proteins repurpose cellular RNA polymerase (Pol II) for viral transcription. More...

Within the first 15 minutes of infection, herpes simplex virus 1 (HSV-1) immediate early proteins repurpose cellular RNA polymerase (Pol II) for viral transcription. An important role of the viral infected cell protein 27 (ICP27) is to facilitate viral pre-mRNA processing and export of viral mRNA to the cytoplasm. Here, we use precision nuclear run-on followed by deep sequencing (PRO-seq) to characterize transcription of a viral ICP27 null mutant. At 1.5 and 3 hours post infection (hpi) we observed Increased total levels of Pol II on the mutant viral genome and accumulation of Pol II downstream of poly A sites indicating increased levels of initiation and processivity. By 6 hpi Pol II accumulation on specific mutant viral genes was higher than wt virus either at or upstream of poly A signals, depending on the gene. The PRO-seq profile of the ICP27 mutant on late genes at 6 hpi was similar but not identical to that caused by treatment with flavopiridol, a known inhibitor of RNA processivity. This pattern was different from PRO-seq profiles of other α gene mutants, and upon inhibition of viral DNA replication with PAA. Together, these results indicate that ICP27 contributes to the repression of aberrant viral transcription at 1.5 and 3 hpi by inhibiting initiation and decreasing RNA processivity. However, ICP27 is needed to enhance processivity on most late genes by 6 hpi in a mechanism distinguishable from its role in viral DNA replication. Overall design: To investigate how HSV-1 ICP27 cooperatively functions to alter RNA polymerase processivity during lytic infection before the onset of viral DNA replication Less...