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

107 Citations (Scopus)

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
StatePublished - Oct 1 2006

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Astrocytes
Antiviral Agents
Ligation
HIV-1
RNA Interference
Acids
Interleukin-1
Interferon Regulatory Factor-3
Genes
Viruses
Protein Array Analysis
Vesicular Stomatitis
Virus Replication
Chemokines
Innate Immunity
Virion
Nucleic Acids
Up-Regulation
HIV
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

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.

TLR3 ligation activates an antiviral response in human fetal astrocytes : A role for viperin/cig5. / Rivieccio, Mark A.; Suh, Hyeon Sook; Zhao, Yongmei; Zhao, Meng Liang; Chin, Keh Chuang; Lee, Sunhee C.; Brosnan, Celia F.

In: Journal of Immunology, Vol. 177, No. 7, 01.10.2006, p. 4735-4741.

Research output: Contribution to journalArticle

Rivieccio, MA, Suh, HS, Zhao, Y, Zhao, ML, Chin, KC, Lee, SC & Brosnan, CF 2006, 'TLR3 ligation activates an antiviral response in human fetal astrocytes: A role for viperin/cig5', Journal of Immunology, vol. 177, no. 7, pp. 4735-4741.
Rivieccio MA, Suh HS, Zhao Y, Zhao ML, Chin KC, Lee SC et al. TLR3 ligation activates an antiviral response in human fetal astrocytes: A role for viperin/cig5. Journal of Immunology. 2006 Oct 1;177(7):4735-4741.
Rivieccio, Mark A. ; Suh, Hyeon Sook ; Zhao, Yongmei ; Zhao, Meng Liang ; Chin, Keh Chuang ; Lee, Sunhee C. ; Brosnan, Celia F. / TLR3 ligation activates an antiviral response in human fetal astrocytes : A role for viperin/cig5. In: Journal of Immunology. 2006 ; Vol. 177, No. 7. pp. 4735-4741.
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