Acyclovir or Aβ42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells

Walter J. Lukiw, Jian Guo Cui, Li Yuan Yuan, Partha S. Bhattacharjee, Madelyn Corkern, Christian Clement, Eli M. Kammerman, M. J. Ball, Yuhai Zhao, Patrick M. Sullivan, James M. Hill

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Human brains harbor herpes simplex virus type-1 (HSV-1) DNA, which normally remains quiescent throughout many decades of life. HSV-1 is associated with viral encephalopathy and with the amyloid beta 42 (Aβ42) peptide-enriched lesions that characterize Alzheimer's disease neuropathology. Here we report that infection of human neuronal-glial cells in primary co-culture with HSV-1 induces an irregular hypertrophy of human neuronal-glial cell bodies, an induction of HSV-1 DNA polymerase, and an up-regulation of micro-RNA-146a associated with altered innate-immune responses. Presence of the antiviral acyclovir or soluble Aβ42 peptide significantly attenuated these neuropathological responses. The inhibitory effects of Aβ42 peptide were also observed in an HSV-1-infected CV-1 cell-based viral plaque assay. The results suggest that soluble Aβ42 peptide can invoke non-pathological and anti-viral effects through inactivation of an HSV-1 challenge to human brain cells by simple viral sequestration, viral destruction, or by complex neurogenetic mechanisms.

Original languageEnglish (US)
Pages (from-to)922-927
Number of pages6
JournalNeuroreport
Volume21
Issue number14
DOIs
StatePublished - Oct 6 2010

Keywords

  • acyclovir
  • acyloguanosine
  • Alzheimer's disease
  • amyloid-beta 42 peptide
  • herpes simplex virus type-1
  • inflammation
  • innate immune response
  • miRNA-146a

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Lukiw, W. J., Cui, J. G., Yuan, L. Y., Bhattacharjee, P. S., Corkern, M., Clement, C., Kammerman, E. M., Ball, M. J., Zhao, Y., Sullivan, P. M., & Hill, J. M. (2010). Acyclovir or Aβ42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells. Neuroreport, 21(14), 922-927. https://doi.org/10.1097/WNR.0b013e32833da51a