Modulation of HLA-G expression in human neural cells after neurotropic viral infections.
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-beta) 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.
Lafon
Monique
M
Unité de Neuroimmunologie Virale, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. mlafon@pasteur.fr
Prehaud
Christophe
C
Megret
Françoise
F
Lafage
Mireille
M
Mouillot
Gaël
G
Roa
Michèle
M
Moreau
Philippe
P
Rouas-Freiss
Nathalie
N
Carosella
Edgardo D
ED
D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D059951:HLA-G Antigens; D018259:Herpesvirus 1, Human / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009420:Nervous System / Q000473:pathology / Q000821:virology*; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis; D011820:Rabies virus / Q000502:physiology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger