Activation of Toll-like receptor-3 induces interferon-λ expression in human neuronal cells

L. Zhou, X. Wang, Y. J. Wang, Y. Zhou, S. Hu, L. Ye, W. Hou, H. Li, W. Z. Ho

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

We examined the gene expression and regulation of type III human interferon (IFN), IFN-λ, in human neuronal cells. Human neuronal cells expressed endogenous IFN-λ1 but not IFN-λ2/3. Upon the activation of Toll-like receptor (TLR)-3 expressed in the neuronal cells by polyriboinosinic polyribocytidylic acid (PolyI:C), both IFN-λ1 and IFN-λ2/3 expression was significantly induced. The activation of TLR-3 also exhibited antiviral activity against pseudotyped human immunodeficiency virus (HIV)-1 infection of the neuronal cells. Human neuronal cells also expressed functional IFN-λ receptor complex, interleukin-28 receptor α subunit (IL-28Rα) and IL-10Rβ, as evidenced by the observations that exogenous IFN-λ treatment inhibited pseudotyped HIV-1 infection of the neuronal cells and induced the expression of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)3G/3F, the newly identified anti-HIV-1 cellular factors. These data provide direct and compelling evidence that there is intracellular expression and regulation of IFN-λ in human neuronal cells, which may have an important role in the innate neuronal protection against viral infections in the CNS.

Original languageEnglish (US)
Pages (from-to)629-637
Number of pages9
JournalNeuroscience
Volume159
Issue number2
DOIs
StatePublished - Mar 17 2009

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health grants DA025477, DA12815 and DA022177 (to W.Z.H.) and the Foerderer Fund from the Children's Hospital of Philadelphia. Lin Zhou is the scholarship recipient of the China Scholarship Council.

Keywords

  • HIV
  • NT2-N
  • Toll-like receptor
  • interferon
  • neuron
  • virus

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