Activation of Toll-like receptors inhibits herpes simplex virus-1 infection of human neuronal cells

J Neurosci Res. 2009 Oct;87(13):2916-25. doi: 10.1002/jnr.22110.


Toll-like receptors (TLRs) play an essential role in initiating intracellular type I interferon (IFN)-mediated innate immunity against viral infections. We examined whether human neuronal cells (primary human neurons, NT2-N and CHP-212 cells) express TLRs and mount type I IFN-mediated innate immunity against herpes simplex virus-1 (HSV-1) infection. Human neuronal cells expressed TLR family members 1-10 and IFN-alpha/beta. The activation of TLR3 or TLR8 by double-stranded RNA (poly-I:C) or single-stranded RNA (ssRNA) induced IFN-alpha/beta expression. In addition, HSV-1 infection of human neuronal cells induced IFN-alpha expression. Investigation of the mechanisms showed that poly-I:C or ssRNA treatment enhanced the expression of several IFN regulatory factors. Importantly, the activation of TLR3 or TLR8 by poly-I:C or ssRNA prior to HSV-1 infection reduced the susceptibility of the neuronal cells to infection. These observations indicate that human neuronal cells possess intracellular TLR-mediated innate immune protection against HSV-1 infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / virology
  • Cells, Cultured / drug effects
  • Cells, Cultured / virology
  • Gene Expression Regulation / drug effects
  • Herpesvirus 1, Human / physiology*
  • Humans
  • Immunity, Innate
  • Interferon Inducers / pharmacology*
  • Interferon Regulatory Factors / biosynthesis
  • Interferon Regulatory Factors / genetics
  • Interferon-alpha / biosynthesis
  • Interferon-alpha / genetics
  • Interferon-beta / biosynthesis
  • Interferon-beta / genetics
  • Neuroblastoma / pathology
  • Neurons / drug effects
  • Neurons / virology*
  • Poly I-C / pharmacology*
  • RNA / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 3 / physiology*
  • Toll-Like Receptor 8 / physiology*
  • Toll-Like Receptors / biosynthesis
  • Toll-Like Receptors / genetics


  • Interferon Inducers
  • Interferon Regulatory Factors
  • Interferon-alpha
  • TLR3 protein, human
  • TLR8 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 8
  • Toll-Like Receptors
  • RNA
  • Interferon-beta
  • Poly I-C