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Submitted on April 5, 2006
Accepted on September 1, 2006
Herpes Simplex Virus Encephalitis in Human UNC-93B Deficiency
Armanda Casrouge 1, Shen-Ying Zhang 2, Céline Eidenschenk 1, Emmanuelle Jouanguy 2, Anne Puel 1, Kun Yang 2, Alexandre Alcais 1, Capucine Picard 3, Nora Mahfoufi 1, Nathalie Nicolas 1, Lazaro Lorenzo 1, Sabine Plancoulaine 1, Brigitte Sénéchal 4, Frédéric Geissmann 4, Koichi Tabeta 5, Kasper Hoebe 6, Xin Du 6, Richard L. Miller 7, Bénédicte Héron 8, Cyril Mignot 8, Thierry Billette de Villemeur 8, Pierre Lebon 9, Olivier Dulac 10, Flore Rozenberg 9, Bruce Beutler 6, Marc Tardieu 11, Laurent Abel 1, Jean-Laurent Casanova 12*
1 Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes-INSERM U550, Faculté de Médecine Necker, Paris 75015, France. 2 Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes-INSERM U550, Faculté de Médecine Necker, Paris 75015, France; French-Chinese Laboratory of Genomics and Life Sciences, Rui-jin Hospital, Shanghai Jiaotong University, Shanghai 200025, China. 3 Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes-INSERM U550, Faculté de Médecine Necker, Paris 75015, France; Centre d'Etude des Déficits Immunitaires, Hôpital Necker, Paris 75015, France. 4 Laboratoire d'Etude des Cellules Mononucléées, Hôpital Necker, Paris 75015, France. 5 Scripps Research Institute, La Jolla, CA 92037, USA; Present address: Niigata University Graduate School of Medical & Dental Sciences, Niigata 951-8514, Japan. 6 Scripps Research Institute, La Jolla, CA 92037, USA. 7 3M Center, St. Paul, MN 55144, USA. 8 Service de Neurologie Pédiatrique, Hôpital Trousseau, Paris 75012, France. 9 Service de Virologie, Hôpital Saint-Vincent de Paul, Paris 75014, France. 10 Service de Neurologie Pédiatrique, Hôpital Necker, Paris 75015, France. 11 Service de Neurologie Pédiatrique et INSERM U802, Hôpital de Bicêtre, Kremlin-Bicêtre 94270, France. 12 Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes-INSERM U550, Faculté de Médecine Necker, Paris 75015, France; French-Chinese Laboratory of Genomics and Life Sciences, Rui-jin Hospital, Shanghai Jiaotong University, Shanghai 200025, China; Unité d'Immunologie et d'Hématologie Pédiatriques, Hôpital Necker, Paris 75015, France.
* To whom correspondence should be addressed.
Jean-Laurent Casanova , E-mail: casanova{at}necker.fr
Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the mostcommon form of sporadic viral encephalitis in western countries.Its pathogenesis remains unclear, as it affects otherwise healthypatients and only a small minority of HSV-1-infected individuals.Here, we elucidate a genetic etiology for HSE in two childrenwith autosomal recessive deficiency in the intracellular proteinUNC-93B, resulting in impaired cellular interferon (IFN)-/ and- antiviral responses. HSE can result from a single-gene immunodeficiencythat does not compromise immunity to most pathogens, unlikemost known primary immunodeficiencies. Other severe infectiousdiseases may also reflect monogenic disorders of immunity thatdo not predispose to multiple infections.
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antiviral responses. HSE can result from a single-gene immunodeficiency that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Other severe infectious diseases may also reflect monogenic disorders of immunity that do not predispose to multiple infections.
