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-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.
Division of Virology, Wuhan Centers for Disease Control and Prevention, Wuhan, China.
Yu
Y
Zhou
Li
L
Ye
Qi
Q
Wan
Lin
L
Zhou
Xu
X
Wang
Jieliang
J
Li
Shuxian
S
Hu
Dunjin
D
Zhou
Wenzhe
W
Ho
D045744:Cell Line, Tumor / Q000187:drug effects / Q000821:virology; D002478:Cells, Cultured / Q000187:drug effects / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007369:Interferon Inducers / Q000494:pharmacology*; D050835:Interferon Regulatory Factors / Q000096:biosynthesis / Q000235:genetics; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000821:virology*; D011070:Poly I-C / Q000494:pharmacology*; D012313:RNA / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000502:physiology*; D051200:Toll-Like Receptor 8 / Q000502:physiology*; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics
D007369:Interferon Inducers; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; C495344:TLR3 protein, human; C495349:TLR8 protein, human; D051196:Toll-Like Receptor 3; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors; D012313:RNA; D016899:Interferon-beta; D011070:Poly I-C