HSEPID

Investigating the genetic architecture and pathogenesis of of Herpes Simplex encephalitis susceptibility

 Coordinatore IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE 

 Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ

contact info
Titolo: Ms.
Nome: Tatjana
Cognome: Palalic
Email: send email
Telefono: +44 207 594 3866

 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 30˙000 €
 EC contributo 30˙000 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-2010-RG
 Funding Scheme MC-ERG
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-01-12   -   2014-01-11

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE

 Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ

contact info
Titolo: Ms.
Nome: Tatjana
Cognome: Palalic
Email: send email
Telefono: +44 207 594 3866

UK (LONDON) coordinator 30˙000.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

viral    simplex    pathogenesis    cells    patients    hope    herpes    dsrna    tested    virus    encephalitis    children    infection    single    hse    immunity    gene    genes    childhood    cns    ifn    mutations    hsv    tlr    cellular   

 Obiettivo del progetto (Objective)

'Childhood herpes simplex encephalitis (HSE) is a potentially life-threatening complication of primary infection by herpes simplex virus-1 (HSV-1), a common virus that is innocuous in most children. HSE is the most common sporadic viral encephalitis in Western countries and acyclovir-treated patients often suffer from severe neurological sequels. The pathogenesis of HSE remained unknown until the recent discoveries of Mendelian single-gene mutations specifically impairing immunity to HSV-1 at least in a subset of children suffering from HSE. We have identified mutations in TLR3, UNC93B, TRIF and TRAF3 in patients with isolated HSE, suggesting that impaired type I interferon (IFN) production upon stimulation of TLR3 by dsRNA viral intermediates in the CNS underlies the pathogenesis of HSE in these patients. Despite the identification of these genes, only a minority of the patients tested carried these genetic defects. Hence we hypothesize that childhood HSE is a genetically heterogeneous disease and that other single gene inborn errors of immunity may explain HSE in other patients. As a first objective, we hope to identify novel HSE-causing genes following a candidate gene approach in patients with a cellular phenotype. The TLR3-IFN pathway will be tested and the known genes sequenced. For those without any mutations in known genes, alternative approaches such as cDNA complementation and RNA sequencing will be carried out. In addition, we also aim to understand the cellular basis of the pathogensis of HSE as most our studies have been carried out on patients’ fibroblasts. We hope to characterize the TLR3-dependent type I IFN production in response to dsRNA and HSV-1 in CNS resident cells by differentiating patient-derived fibroblast induced pluripotent stem (iPS) cells into neurons, oligodendrocytes, and astrocytes. Investigating the anti-HSV-1 immunity in the relevant CNS cells types will be important in furthering our understanding of HSE pathogenesis.'

Introduzione (Teaser)

Human herpes simplex virus-1 (HSV-1) is probably one of the most common childhood infections and results in cold sores. An EU-funded research project has looked into the genes that prevent the virus developing into a brain infection.

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