TLR3 ligation activates an antiviral response in human fetal astrocytes: A role for viperin/cig5

Mark A. Rivieccio, Hyeon Sook Suh, Yongmei Zhao, Meng Liang Zhao, Keh Chuang Chin, Sunhee C. Lee, Celia F. Brosnan

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

TLR3 functions as a viral nucleic acid sentinel activated by dsRNA viruses and virus replication intermediates within intracellular vesicles. To explore the spectrum of genes induced in human astrocytes by TLR3, we used a microarray approach and the analog polyriboinosinic polyribocytidylic acid (pIC) as ligand. As expected for TLR activation, pIC induced a wide array of cytokines and chemokines known for their role in inflammatory responses, as well as up-regulation of the receptor itself. The data also showed activation of a broad spectrum of antiviral response genes. To determine whether pIC induced an antiviral state in astrocytes, a pseudotyped HIV viral particle, vesicular stomatitis virus g-env-HIV-1, was used. pIC significantly abrogated HIV-1 replication, whereas IL-1, which also potently activates astrocytes, did not. One of the most highly up-regulated genes on microarray was the protein viperin/cig5. We found that viperin/cig5 expression was dependent on IFN regulatory factor 3 and NF-κB signaling, and that repetitive stimulation with pIC, but not IL-1, further increased expression. Viperin induction could also be substantially inhibited by neutralizing Abs to IFN-β, as could HIV-1 replication. To explore a role for viperin in IFN-β-mediated inhibition of HIV-1, we used an RNA interference (RNAi) approach. RNAi directed against viperin, bat not a scrambled RNAi, significantly inhibited viperin expression, and also significantly reversed pIC-induced inhibition of HIV-1 replication. We conclude that viperin contributes to the antiviral state induced by TLR3 ligation in astrocytes, supporting a role for astrocytes as part of the innate immune response against infection in the CNS.

Original languageEnglish (US)
Pages (from-to)4735-4741
Number of pages7
JournalJournal of Immunology
Volume177
Issue number7
DOIs
StatePublished - Oct 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rivieccio, M. A., Suh, H. S., Zhao, Y., Zhao, M. L., Chin, K. C., Lee, S. C., & Brosnan, C. F. (2006). TLR3 ligation activates an antiviral response in human fetal astrocytes: A role for viperin/cig5. Journal of Immunology, 177(7), 4735-4741. https://doi.org/10.4049/jimmunol.177.7.4735