A neuron-specific host microRNA targets herpes simplex virus-1 ICP0 expression and promotes latency.

Journal Article (Journal Article)

After infecting peripheral sites, herpes simplex virus (HSV) invades the nervous system and initiates latent infection in sensory neurons. Establishment and maintenance of HSV latency require host survival, and entail repression of productive cycle ("lytic") viral gene expression. We find that a neuron-specific microRNA, miR-138, represses expression of ICP0, a viral transactivator of lytic gene expression. A mutant HSV-1 (M138) with disrupted miR-138 target sites in ICP0 mRNA exhibits enhanced expression of ICP0 and other lytic proteins in infected neuronal cells in culture. Following corneal inoculation, M138-infected mice have higher levels of ICP0 and lytic transcripts in trigeminal ganglia during establishment of latency, and exhibit increased mortality and encephalitis symptoms. After full establishment of latency, the fraction of trigeminal ganglia harboring detectable lytic transcripts is greater in M138-infected mice. Thus, miR-138 is a neuronal factor that represses HSV-1 lytic gene expression, promoting host survival and viral latency.

Full Text

Duke Authors

Cited Authors

  • Pan, D; Flores, O; Umbach, JL; Pesola, JM; Bentley, P; Rosato, PC; Leib, DA; Cullen, BR; Coen, DM

Published Date

  • April 9, 2014

Published In

Volume / Issue

  • 15 / 4

Start / End Page

  • 446 - 456

PubMed ID

  • 24721573

Pubmed Central ID

  • PMC4142646

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2014.03.004


  • eng

Conference Location

  • United States