Kinetics of Facultative Heterochromatin and Polycomb Group Protein Association with the Herpes Simplex Viral Genome during Establishment of Latent Infection

Abstract

The human pathogen herpes simplex virus (HSV) hides for the lifetime of the host in peripheral neurons. The mechanism by which HSV is able to shut off its gene expression and persist in neurons is not known. Here we show that the HSV DNA first associates with histone H3, with later recruitment of Polycomb repressor complex 2 (PRC2) and trimethylation of the lysine 27 residue of histone H3 (H3K27me3), a modification associated with heterochromatin. This work indicates that the initial silencing of HSV gene expression is not correlated with enrichment of H3K27me3 and that PRC2 may be recruited to already-silenced genes to further silence gene expression and/or maintain gene silencing. We demonstrate that recruitment of PRC2 is not dependent upon expression of the noncoding HSV latency-associated transcripts, indicating the presence of unknown triggers for PRC2 recruitment during the establishment of latent infection.