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Journal of Virology, December 2005, p. 15226-15237, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15226-15237.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Modulation of HLA-G Expression in Human Neural Cells after Neurotropic Viral Infections

Monique Lafon,1* Christophe Prehaud,1 Françoise Megret,1 Mireille Lafage,1 Gaël Mouillot,2 Michèle Roa,1 Philippe Moreau,2 Nathalie Rouas-Freiss,2 and Edgardo D. Carosella2

Unité de Neuroimmunologie Virale, Institut Pasteur, Paris, France,1 Service de Recherche en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint Louis, IUH, Paris, France2

Received 30 June 2005/ Accepted 7 September 2005

HLA-G is a nonclassical human major histocompatibility complex class I molecule. It may promote tolerance, leading to acceptance of the semiallogeneic fetus and tumor immune escape. We show here that two viruses—herpes simplex virus type 1 (HSV-1), a neuronotropic virus inducing acute infection and neuron latency; and rabies virus (RABV), a neuronotropic virus triggering acute neuron infection—upregulate the neuronal expression of several HLA-G isoforms, including HLA-G1 and HLA-G5, the two main biologically active isoforms. RABV induces mostly HLA-G1, and HSV-1 induces mostly HLA-G3 and HLA-G5. HLA-G expression is upregulated in infected cells and neighboring uninfected cells. Soluble mediators, such as beta interferon (IFN-ß) and IFN-{gamma}, upregulate HLA-G expression in uninfected cells. The membrane-bound HLA-G1 isoform was detected on the surface of cultured RABV-infected neurons but not on the surface of HSV-1-infected cells. Thus, neuronotropic viruses that escape the host immune response totally (RABV) or partially (HSV-1) regulate HLA-G expression on human neuronal cells differentially. HLA-G may therefore be involved in the escape of certain viruses from the immune response in the nervous system.

* Corresponding author. Mailing address: Unité de Neuroimmunologie Virale, Institut Pasteur, 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.

Journal of Virology, December 2005, p. 15226-15237, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15226-15237.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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