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J Virol. 2016 Sep 7. pii: JVI.01220-16. [Epub ahead of print]

Canonical and variant forms of histone H3 are deposited onto the human cytomegalovirus genome during lytic and latent infections.

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Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison WI 53716 USA.
Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison WI 53716 USA


Chromatin is the nucleoprotein complex that protects and compacts eukaryotic genomes. It is responsible for a large part of the epigenetic control of transcription. The genomes of DNA viruses such as human cytomegalovirus (HCMV) are devoid of histones within virions but are chromatinized and epigenetically regulated following delivery to the host cell nucleus. How chromatin is initially assembled on viral genomes, and which variant forms of the core histone proteins are deposited is incompletely understood. We monitored the deposition of both ectopically expressed and endogenous histone H3.1/2 and H3.3 during lytic and latent HCMV infections. Here we show both are deposited on HCMV genomes during lytic and latent infections suggesting similar mechanisms of viral chromatin assembly during the different infection types and indicating both canonical and variant core histones may be important modulators of infecting viral genomes. We further show that association of both H3.1/2 and H3.3 occurs independent of viral DNA synthesis or de novo viral gene expression, implicating cellular factors and/or virion components in the formation of chromatin on virion-delivered genomes during both lytic and latent infections.


It is well established that infecting herpesvirus genomes are chromatinized upon entry into the host cell nucleus. Why or how this occurs is a mystery. It is important to know why they are chromatinized in order to better understand cellular pathogen recognition (DNA sensing) pathways, viral fate determinations (lytic or latent), and to anticipate how artificially modulating chromatinization may impact viral infections. It is important to know how they are chromatinized in order to potentially modulate the process for therapeutic effect. Our work showing HCMV genomes are loaded with canonical and variant H3 histones during both lytic and latent infections strengthens the hypothesis that chromatinization pathways are similar between the two infection types, implicates virion or cellular factors in this process, and exposes the possibility that histone variants, in addition to post-translational modification, may impact viral gene expression. These revelations are important to understanding and intelligently intervening in herpesvirus infections.

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