Document Detail


Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans.
MedLine Citation:
PMID:  17989525     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Herpes simplex encephalitis is a rare complication of herpes simplex virus 1 infection that strikes otherwise healthy individuals. Its pathogenesis has long remained elusive. We highlight the investigations dealing with the genetic basis of herpes simplex encephalitis in mice and humans. RECENT FINDINGS: Mouse models have revealed the impact of various host genes on protective immunity to herpes simplex encephalitis through strain-dependent variability (forward genetics) and via targeted knockouts (reverse genetics). These studies established in particular the crucial role of IFNalpha/beta in immunity to herpes simplex virus 1, paving the way towards the elucidation of the genetic cause of human herpes simplex encephalitis. Two children with rare, specific STAT1 or NEMO mutations displayed a broad impairment of IFNalpha/beta and IFNlambda-mediated immunity and predisposition to several infectious diseases including herpes simplex encephalitis. In contrast, children with UNC93B1 and TLR3 mutations displayed a selective impairment of dsRNA-induced IFNalpha/beta and IFNlambda production and predisposition to isolated herpes simplex encephalitis. SUMMARY: Herpes simplex encephalitis results from a series of monogenic primary immunodeficiencies that impair the TLR3 and UNC-93B-dependent production of IFNalpha/beta and IFNlambda in the central nervous system, at least in a fraction of children. This is not only crucial for the understanding of immunity to herpes simplex virus 1, but also for the diagnosis and treatment of herpes simplex encephalitis.
Authors:
Vanessa Sancho-Shimizu; Shen-Ying Zhang; Laurent Abel; Marc Tardieu; Flore Rozenberg; Emmanuelle Jouanguy; Jean-Laurent Casanova
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in allergy and clinical immunology     Volume:  7     ISSN:  1528-4050     ISO Abbreviation:  Curr Opin Allergy Clin Immunol     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-08     Completed Date:  2008-03-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100936359     Medline TA:  Curr Opin Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  495-505     Citation Subset:  IM    
Affiliation:
Laboratory of Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Encephalitis, Herpes Simplex / genetics*,  immunology
Genetic Predisposition to Disease
Herpesvirus 1, Human / genetics,  immunology*
Humans
I-kappa B Kinase / genetics,  immunology
Interferon Type I / immunology
Interferon-gamma / immunology
Membrane Transport Proteins / genetics,  immunology
Mice
STAT1 Transcription Factor / genetics,  immunology
Toll-Like Receptor 3 / genetics,  immunology
Chemical
Reg. No./Substance:
0/IKBKG protein, human; 0/Interferon Type I; 0/Membrane Transport Proteins; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/TLR3 protein, human; 0/Toll-Like Receptor 3; 0/UNC93B1 protein, human; 82115-62-6/Interferon-gamma; EC 2.7.11.10/I-kappa B Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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