During lytic
infection, herpes simplex virus type 1 (HSV-1) represses host transcription, recruits
RNA polymerase II (RNAP II) to viral replication compartments, and alters the phosphorylation state of the RNAP II large subunit. Host transcription repression and RNAP II modifications require expression of viral immediate-early (IE) genes. Efficient modification of the RNAP II large subunit to the intermediately phosphorylated (IIi) form requires expression of ICP22 and the UL13
kinase. We have further investigated the mechanisms by which HSV-1 effects global changes in RNAP II transcription by analyzing the RNAP II
holoenzyme. We find that the RNAP II
general transcription factors (GTFs) remain abundant after
infection and are recruited into viral replication compartments, suggesting that they continue to be involved in viral gene transcription. However,
virus infection modifies the composition of the RNAP II
holoenzyme, in particular triggering the loss of the essential GTF,
TFIIE. Loss of
TFIIE from the RNAP II
holoenzyme requires viral IE gene expression, and viral IE
proteins may be redundant in mediating this effect. Although viral IE
proteins do not associate with the RNAP II
holoenzyme, they interact with RNAP II in complexes of lower molecular mass. As the RNAP II
holoenzyme containing
TFIIE is necessary for activated transcription initiation and RNAP II large subunit phosphorylation in uninfected cells, virus-induced modifications to the
holoenzyme may affect both of these processes, leading to aberrant phosphorylation of the RNAP II large subunit and repression of host gene transcription.