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Originally published in Science Express on 14 September 2006
Science 13 October 2006:
Vol. 314. no. 5797, pp. 308 - 312
DOI: 10.1126/science.1128346
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Reports

Herpes Simplex Virus Encephalitis in Human UNC-93B Deficiency

Armanda Casrouge,1* Shen-Ying Zhang,1,2* Céline Eidenschenk,1* Emmanuelle Jouanguy,1,2* Anne Puel,1 Kun Yang,1,2 Alexandre Alcais,1 Capucine Picard,1,3 Nora Mahfoufi,1 Nathalie Nicolas,1 Lazaro Lorenzo,1 Sabine Plancoulaine,1 Brigitte Sénéchal,4 Frédéric Geissmann,4 Koichi Tabeta,5{dagger} Kasper Hoebe,5 Xin Du,5 Richard L. Miller,6 Bénédicte Héron,7 Cyril Mignot,7 Thierry Billette de Villemeur,7 Pierre Lebon,8 Olivier Dulac,9 Flore Rozenberg,8 Bruce Beutler,5 Marc Tardieu,10 Laurent Abel,1 Jean-Laurent Casanova1,2,11{ddagger}

Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral encephalitis in western countries. Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority of HSV-1–infected individuals. Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in the intracellular protein UNC-93B, resulting in impaired cellular interferon-{alpha}/ß and -{lambda} 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.

1 Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes, INSERM, U550, Faculté de Médecine Necker, Paris 75015, France.
2 French-Chinese Laboratory of Genomics and Life Sciences, Rui-jin Hospital, Shanghai Jiaotong University, Shanghai 200025, China.
3 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.
6 3M Center, St. Paul, MN 55144, USA.
7 Service de Neurologie Pédiatrique, Hôpital Trousseau, Paris 75012, France.
8 Service de Virologie, Hôpital Saint-Vincent de Paul, Paris 75014, France.
9 Service de Neurologie Pédiatrique, Hôpital Necker, Paris 75015, France.
10 Service de Neurologie Pédiatrique et INSERM U802, Hôpital de Bicêtre, Kremlin-Bicêtre 94270, France.
11 Unité d'Immunologie et d'Hématologie Pédiatriques, Hôpital Necker, Paris 75015, France.

* These authors contributed equally to this work.

{dagger} Present address: Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.

{ddagger} To whom correspondence should be addressed. E-mail: casanova{at}necker.fr

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