Skip to main content
European Commission logo
Deutsch Deutsch
CORDIS - Forschungsergebnisse der EU
CORDIS
CORDIS Web 30th anniversary CORDIS Web 30th anniversary
Inhalt archiviert am 2024-06-18

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

Ziel

"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."

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2010-RG
Andere Projekte für diesen Aufruf anzeigen

Koordinator

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
EU-Beitrag
€ 30 000,00
Adresse
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ LONDON
Vereinigtes Königreich

Auf der Karte ansehen

Region
London Inner London — West Westminster
Aktivitätstyp
Higher or Secondary Education Establishments
Kontakt Verwaltung
Tatjana Palalic (Ms.)
Links
Gesamtkosten
Keine Daten