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Journal of Virology, October 2005, p. 12893-12904, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12893-12904.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Virus Infection Switches TLR-3-Positive Human Neurons To Become Strong Producers of Beta Interferon

Christophe Préhaud,{dagger} Françoise Mégret,{dagger} Mireille Lafage, and Monique Lafon*

Unité de Neuroimmunologie Virale, Institut Pasteur, Paris, France

Received 19 April 2005/ Accepted 18 July 2005

To study the capacity of human neurons to mount innate immunity responses to viral infections, we infected cells of a human postmitotic neuron-derivative cell line, NT2-N, with rabies virus (RABV) and herpes simplex type 1 (HSV-1). Changes in neuronal gene expression were analyzed by use of Affymetrix microarrays. Applying a twofold cutoff, RABV increased the transcription of 228 genes, and HSV-1 increased the transcription of 263 genes. The most striking difference between the two infections concerns genes involved in immunity. These genes represent 24% of the RABV-upregulated genes and only 4.9% of the HSV-1-upregulated genes. Following RABV infection, the most upregulated genes belong to the immunity cluster and included almost exclusively genes for beta interferon (IFN-ß) primary and secondary responses as well as genes for chemokines (CCL-5, CXCL-10) and inflammatory cytokines (interleukin 6 [IL-6], tumor necrosis factor alpha, interleukin 1 alpha). In contrast, HSV-1 infection did not increase IFN-ß gene transcripts and triggered the production of only IL-6 and interferon regulatory factor 1 mRNAs. The microarray results were confirmed by real-time PCR, immunocytochemistry, and enzyme-linked immunosorbent assay. Human neurons were found to express Toll-like receptor 3. They produced IFN-ß after treatment with poly(I:C) but not with lipopolysaccharide. Thus, human neurons can mount an innate immunity response to double-stranded RNA. These observations firmly establish that human neurons, in absence of glia, have the intrinsic machinery to sense virus infection.

* Corresponding author. Mailing address: 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33 1 45 68 87 52. Fax: 33 1 40 61 33 12. E-mail: mlafon{at}pasteur.fr.

{dagger} These authors contributed equally to this work.

Journal of Virology, October 2005, p. 12893-12904, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12893-12904.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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