Document Detail


Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency.
MedLine Citation:
PMID:  22105173     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Herpes simplex encephalitis (HSE) is the most common sporadic viral encephalitis of childhood. Autosomal recessive (AR) UNC-93B and TLR3 deficiencies and autosomal dominant (AD) TLR3 and TRAF3 deficiencies underlie HSE in some children. We report here unrelated HSE children with AR or AD TRIF deficiency. The AR form of the disease was found to be due to a homozygous nonsense mutation that resulted in a complete absence of the TRIF protein. Both the TLR3- and the TRIF-dependent TLR4 signaling pathways were abolished. The AD form of disease was found to be due to a heterozygous missense mutation, resulting in a dysfunctional protein. In this form of the disease, the TLR3 signaling pathway was impaired, whereas the TRIF-dependent TLR4 pathway was unaffected. Both patients, however, showed reduced capacity to respond to stimulation of the DExD/H-box helicases pathway. To date, the TRIF-deficient patients with HSE described herein have suffered from no other infections. Moreover, as observed in patients with other genetic etiologies of HSE, clinical penetrance was found to be incomplete, as some HSV-1-infected TRIF-deficient relatives have not developed HSE. Our results provide what we believe to be the first description of human TRIF deficiency and a new genetic etiology for HSE. They suggest that the TRIF-dependent TLR4 and DExD/H-box helicase pathways are largely redundant in host defense. They further demonstrate the importance of TRIF for the TLR3-dependent production of antiviral IFNs in the CNS during primary infection with HSV-1 in childhood.
Authors:
Vanessa Sancho-Shimizu; Rebeca Pérez de Diego; Lazaro Lorenzo; Rabih Halwani; Abdullah Alangari; Elisabeth Israelsson; Sylvie Fabrega; Annabelle Cardon; Jerome Maluenda; Megumi Tatematsu; Farhad Mahvelati; Melina Herman; Michael Ciancanelli; Yiqi Guo; Zobaida AlSum; Nouf Alkhamis; Abdulkarim S Al-Makadma; Ata Ghadiri; Soraya Boucherit; Sabine Plancoulaine; Capucine Picard; Flore Rozenberg; Marc Tardieu; Pierre Lebon; Emmanuelle Jouanguy; Nima Rezaei; Tsukasa Seya; Misako Matsumoto; Damien Chaussabel; Anne Puel; Shen-Ying Zhang; Laurent Abel; Saleh Al-Muhsen; Jean-Laurent Casanova
Related Documents :
15964103 - Live-attenuated intranasal parainfluenza virus type 2 vaccine candidates developed by r...
2369733 - Molecular nature of in vivo mutations in human cells at the autosomal hla-a locus.
17121793 - Mutually exclusive t-cell receptor induction and differential susceptibility to human i...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-21
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-02     Completed Date:  2012-01-31     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4889-902     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Necker Medical School, Paris, France. vanessa.sancho-shimizu@inserm.fr
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE32390
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Vesicular Transport / deficiency*,  genetics,  physiology
Amino Acid Sequence
Child, Preschool
Codon, Nonsense
Consanguinity
DEAD-box RNA Helicases / physiology
Encephalitis, Herpes Simplex / genetics*
Female
Genes, Dominant
Genes, Recessive
Genetic Heterogeneity
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Herpesvirus 1, Human*
Humans
Infant
Interferon-alpha / biosynthesis,  genetics
Male
Molecular Sequence Data
Mutation, Missense
Pedigree
Saudi Arabia
Sequence Alignment
Sequence Homology, Amino Acid
Signal Transduction / physiology
Toll-Like Receptor 3 / physiology
Toll-Like Receptor 4 / physiology
Grant Support
ID/Acronym/Agency:
5UL1RR024143-03/RR/NCRR NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Vesicular Transport; 0/Codon, Nonsense; 0/Interferon-alpha; 0/TICAM1 protein, human; 0/TLR3 protein, human; 0/TLR4 protein, human; 0/Toll-Like Receptor 3; 0/Toll-Like Receptor 4; EC 3.6.1.-/DEAD-box RNA Helicases
Comments/Corrections

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


Previous Document:  Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration.
Next Document:  Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with condi...