title: Cellular defense against latent colonization foiled by human cytomegalovirus UL138 protein.
abstract: Intrinsic immune defenses mediated by restriction factors inhibit productive viral infections. Select viruses rapidly establish latent infections and, with gene expression profiles that imply cell-autonomous intrinsic defenses, may be the most effective immune control measure against latent reservoirs. We illustrate that lysine-specific demethylases (KDMs) are restriction factors that prevent human cytomegalovirus from establishing latency by removing repressive epigenetic modifications from histones associated with the viral major immediate early promoter (MIEP), stimulating the expression of a viral lytic phase target of cell-mediated adaptive immunity. The viral UL138 protein negates this defense by preventing KDM association with the MIEP. The presence of an intrinsic defense against latency and the emergence of a cognate neutralizing viral factor indicate that "arms races" between hosts and viruses over lifelong colonization exist at the cellular level.
authors.affiliation: Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Song Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Albright
authors.affiliation: Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Derek
authors.identifier: 0000-0003-0676-8064
authors.initials: D
authors.lastname: Jacobs
authors.affiliation: Institute for Molecular Virology and McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Kalejta
keywords: Epigenetics; cytomegalovirus; herpes; restriction; transcription