title: Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Laboratory of Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale, Paris, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sancho-Shimizu
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Marc
authors.initials: M
authors.lastname: Tardieu
authors.forename: Flore
authors.initials: F
authors.lastname: Rozenberg
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jouanguy
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020803:Encephalitis, Herpes Simplex / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology
chemical_list: C491731:IKBKG protein, human; D007370:Interferon Type I; D026901:Membrane Transport Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; C454130:UNC93B1 protein, human; D007371:Interferon-gamma; D051550:I-kappa B Kinase