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

Authors
  • Pan, Dongli1
  • Flores, Omar2
  • Umbach, Jennifer L2
  • Pesola, Jean M1
  • Bentley, Peris1
  • Rosato, Pamela C3
  • Leib, David A3
  • Cullen, Bryan R2
  • Coen, Donald M4
  • 1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • 2 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
  • 3 Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. , (Lebanon)
  • 4 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell host & microbe
Publication Date
Apr 09, 2014
Volume
15
Issue
4
Pages
446–456
Identifiers
DOI: 10.1016/j.chom.2014.03.004
PMID: 24721573
Source
Medline
License
Unknown

Abstract

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.

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