Research ArticleVIROLOGY

Cellular defense against latent colonization foiled by human cytomegalovirus UL138 protein

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Science Advances  27 Nov 2015:
Vol. 1, no. 10, e1501164
DOI: 10.1126/sciadv.1501164


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.

  • cytomegalovirus
  • herpes
  • Epigenetics
  • transcription
  • restriction

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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