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In this study, we analyzed the role of the immuno-inhibitory molecule B7-H1 in this virus strategy. We showed that in the brain and spinal cord of mice, rabies virus infection resulted in significant up-regulation of B7-H1 expression, which is specifically expressed in infected neurons. Correlatively, clinical rabies in B7-H1\u2212\/\u2212 mice is markedly less severe than in wild-type mice. B7-H1\u2212\/\u2212 mice display resistance to rabies. Virus invasion is reduced and the level of migratory CD8 T cells increases into the nervous system, while CD4\/CD8 ratio remains unchanged in the periphery. In vivo, neuronal B7-H1 expression is critically depending on TLR3 signaling and IFN-\u03b2, because TLR3\u2212\/\u2212 mice\u2014in which IFN-\u03b2 production is reduced\u2014showed only a limited increase of B7-H1 transcripts after infection. These data provide evidence that neurons can express the B7-H1 molecule after viral stress or exposure to a particular cytokine environment. They show that the B7-H1\/PD-1 pathway can be exploited locally and in an organ specific manner\u2014here the nervous system\u2014by a neurotropic virus to promote successful host invasion.<\/jats:p>","DOI":"10.4049\/jimmunol.180.11.7506","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:09:57Z","timestamp":1397848197000},"page":"7506-7515","source":"Crossref","is-referenced-by-count":93,"title":["Detrimental Contribution of the Immuno-Inhibitor B7-H1 to Rabies Virus Encephalitis"],"prefix":"10.1093","volume":"180","author":[{"given":"Monique","family":"Lafon","sequence":"first","affiliation":[{"name":"Viral Neuroimmunology, Institut Pasteur , Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc\u0327oise","family":"Me\u0301gret","sequence":"additional","affiliation":[{"name":"Viral Neuroimmunology, Institut Pasteur , Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G","family":"Meuth","sequence":"additional","affiliation":[{"name":"Department of Neurology, Julius-Maximilians-University of Wuerzburg , Wuerzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Julius-Maximilians-University of Wuerzburg , Wuerzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam L","family":"Velandia Romero","sequence":"additional","affiliation":[{"name":"Viral Neuroimmunology, Institut Pasteur , Paris"},{"name":"Instituto de Virologia, Universitad El Bosque , Bogota ,","place":["Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Lafage","sequence":"additional","affiliation":[{"name":"Viral Neuroimmunology, Institut Pasteur , Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Oncology, Johns Hopkins University School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Alexopoulou","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Flavell","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine , New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Prehaud","sequence":"additional","affiliation":[{"name":"Viral Neuroimmunology, Institut Pasteur , Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Wiendl","sequence":"additional","affiliation":[{"name":"Department of Neurology, Julius-Maximilians-University of Wuerzburg , Wuerzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,6,1]]},"reference":[{"key":"2026012809170388900_R1","first-page":"327","volume-title":"Curr. 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