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

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‐α/β. The activation of TLR3 or TLR8 by double‐stranded RNA (poly‐I:C) or single‐stranded RNA (ssRNA) induced IFN‐α/β expression. In addition, HSV‐1 infection of human neuronal cells induced IFN‐α 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. © 2009 Wiley‐Liss, Inc.