TLR3 and TLR4 are innate antiviral immune receptors in human microglia: Role of IRF3 in modulating antiviral and inflammatory response in the CNS

Abstract In the CNS, microglia are the primary targets of HIV infection. In this study, we investigated the effect of activation of the innate antiviral receptors TLR3 and TLR4 on HIV infection of primary human microglia, as well as microglial cell signaling and gene expression. Ligands for both TLR...

Full description

Saved in:
Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2009-09, Vol.392 (2), p.246-259
Main Authors: Suh, Hyeon-Sook, Zhao, Meng-Liang, Choi, Namjong, Belbin, Thomas J, Brosnan, Celia F, Lee, Sunhee C
Format: Article
Language:English
Subjects:
Cells, Cultured
Cytokines
Gene Expression Profiling
HIV
HIV - physiology
HIV Infections - immunology
Human immunodeficiency virus
Humans
Infectious Disease
Interferon Regulatory Factor-3 - immunology
Interferon-beta - immunology
IRF3
Microglia
Microglia - immunology
Microglia - virology
Oligonucleotide Array Sequence Analysis
RNA Interference
Toll-like receptor
Toll-Like Receptor 3 - immunology
Toll-Like Receptor 4 - immunology
Virus Replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract In the CNS, microglia are the primary targets of HIV infection. In this study, we investigated the effect of activation of the innate antiviral receptors TLR3 and TLR4 on HIV infection of primary human microglia, as well as microglial cell signaling and gene expression. Ligands for both TLR3 and TLR4 potently inhibited HIV replication in microglia through a pathway requiring IRF3. Surprisingly, a remarkably similar pattern of cell signaling and gene expression was observed in TLR3- and TLR4-activated microglia, suggesting a relatively minor role for MyD88 following TLR4 activation in these cells. HIV did not activate IRF3 but rather decreased IRF3 protein, indicating that HIV does not activate TLR3 or RIG-like helicases in microglia. Taken together, these results indicate that activation of TLR3 or TLR4 will elicit antiviral immunity, in addition to inducing proinflammatory responses. We suggest that a balanced expression between inflammatory and innate immune genes might be achieved by IRF3 over-expression.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2009.07.001