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bioRxiv · 10.1101/2021.04.09.439230

The herpes simplex virus 1 protein ICP4 acts as both an activator and repressor of host genome transcription during infection

Rivas, T.·Goodrich, J.·Kugel, J.
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Abstract

Infection by Herpes simplex virus 1 (HSV-1) impacts nearly all steps of gene expression in the host cell. The regulatory mechanisms by which this occurs, and the interplay between host and viral factors, have yet to be fully elucidated. Here we investigated how the occupancy of RNA polymerase II (Pol II) on the host genome changes during HSV-1 infection and is impacted by the viral immediate early protein ICP4. Pol II ChIP-seq experiments revealed a reduction of Pol II occupancy across the bodies of hundreds of host genes that was dependent upon ICP4. Concomitantly, Pol II levels increased across the bodies of several hundred genes, the majority of which also depended on ICP4 for activation. Our data suggest ICP4 regulates repression of Pol II at host genes by inhibiting recruitment of Pol II, while it regulates activation by promoting release of Pol II from promoter proximal pausing into productive elongation. Consistent with this, relative levels of the pausing factors NELF-A and Spt5 were reduced on an HSV-1 activated gene in an ICP4 dependent manner. Exogenous expression of ICP4 revealed that ICP4 can activate, but not repress, transcription of some genes in the absence of infection in a manner that correlates with the chromatin state of the gene. Together our data support the model that ICP4 decreases promoter proximal pausing on host genes activated by infection, and ICP4 is necessary, but not sufficient, to repress transcription from host genes during viral infection.

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Rivas, T., Goodrich, J., Kugel, J.. 2021-04-11. The herpes simplex virus 1 protein ICP4 acts as both an activator and repressor of host genome transcription during infection. https://doi.org/10.1101/2021.04.09.439230

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