Infection by Herpes Simplex Virus 1 Causes Near-Complete Loss of RNA Polymerase II Occupancy on the Host Cell Genome

• Published in: Journal of virology 2016-03, Vol.90 (5), p.2503-2513
• Main Authors: Abrisch, Robert G, Eidem, Tess M, Yakovchuk, Petro, Kugel, Jennifer F, Goodrich, James A
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Cellular Response to Infection; Chromatin Immunoprecipitation; DNA - metabolism; Herpesvirus 1, Human - growth & development; Herpesvirus 1, Human - physiology; High-Throughput Nucleotide Sequencing; Host-Pathogen Interactions; Mice; Promoter Regions, Genetic; Protein Binding; RNA Polymerase II - metabolism; Sequence Analysis, DNA; Virus Replication
• ISSN: 0022-538X; 1098-5514; 1098-5514
• DOI: 10.1128/JVI.02665-15

Lytic infection by herpes simplex virus 1 (HSV-1) triggers a change in many host cell programs as the virus strives to express its own genes and replicate. Part of this process is repression of host cell transcription by RNA polymerase II (Pol II), which also transcribes the viral genome. Here, we describe a global characterization of Pol II occupancy on the viral and host genomes in response to HSV-1 infection using chromatin immunoprecipitation followed by deep sequencing (ChIP-seq). The data reveal near-complete loss of Pol II occupancy throughout host cell mRNA genes, in both their bodies and promoter-proximal regions. Increases in Pol II occupancy of host cell genes, which would be consistent with robust transcriptional activation, were not observed. HSV-1 infection induced a more potent and widespread repression of Pol II occupancy than did heat shock, another cellular stress that widely represses transcription. Concomitant with the loss of host genome Pol II occupancy, we observed Pol II covering the HSV-1 genome, reflecting a high level of viral gene transcription. Interestingly, the positions of the peaks of Pol II occupancy at HSV-1 and host cell promoters were different. We investigated the effect of herpes simplex virus 1 (HSV-1) infection on transcription of host cell and viral genes by RNA polymerase II (Pol II). The approach we used was to determine how levels of genome-bound Pol II changed after HSV-1 infection. We found that HSV-1 caused a profound loss of Pol II occupancy across the host cell genome. Increases in Pol II occupancy were not observed, showing that no host genes were activated after infection. In contrast, Pol II occupied the entire HSV-1 genome. Moreover, the pattern of Pol II at HSV-1 genes differed from that on host cell genes, suggesting a unique mode of viral gene transcription. These studies provide new insight into how HSV-1 causes changes in the cellular program of gene expression and how the virus coopts host Pol II for its own use.