MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs.

Journal Article (Journal Article)

Herpesviruses are characterized by their ability to maintain life-long latent infections in their animal hosts. However, the mechanisms that allow establishment and maintenance of the latent state remain poorly understood. Herpes simplex virus 1 (HSV-1) establishes latency in neurons of sensory ganglia, where the only abundant viral gene product is a non-coding RNA, the latency associated transcript (LAT). Here we show that LAT functions as a primary microRNA (miRNA) precursor that encodes four distinct miRNAs in HSV-1 infected cells. One of these miRNAs, miR-H2-3p, is transcribed in an antisense orientation to ICP0-a viral immediate-early transcriptional activator that is important for productive HSV-1 replication and thought to have a role in reactivation from latency. We show that miR-H2-3p is able to reduce ICP0 protein expression, but does not significantly affect ICP0 messenger RNA levels. We also identified a fifth HSV-1 miRNA in latently infected trigeminal ganglia, miR-H6, which derives from a previously unknown transcript distinct from LAT. miR-H6 shows extended seed complementarity to the mRNA encoding a second HSV-1 transcription factor, ICP4, and inhibits expression of ICP4, which is required for expression of most HSV-1 genes during productive infection. These results may explain the reported ability of LAT to promote latency. Thus, HSV-1 expresses at least two primary miRNA precursors in latently infected neurons that may facilitate the establishment and maintenance of viral latency by post-transcriptionally regulating viral gene expression.

Full Text

Duke Authors

Cited Authors

  • Umbach, JL; Kramer, MF; Jurak, I; Karnowski, HW; Coen, DM; Cullen, BR

Published Date

  • August 7, 2008

Published In

Volume / Issue

  • 454 / 7205

Start / End Page

  • 780 - 783

PubMed ID

  • 18596690

Pubmed Central ID

  • PMC2666538

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature07103


  • eng

Conference Location

  • England