Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency

Sancho‐Shimizu, Vanessa; Diego, Rebeca Pérez de; Lorenzo, Lazaro; Halwani, Rabih; Alangari, Abdullah; Israelsson, Elisabeth; Fabrega, Sylvie; Cardon, Annabelle; Maluenda, Jérôme; Tatematsu, Megumi; Mahvelati, F.; Herman, Melina; Ciancanelli, Michael J.; Guo, Yiqi; Alsum, Zobaida; Alkhamis, Nouf; Al-Makadma, Abdulkarim S.; Ghadiri, Ataallah; Boucherit, Soraya; Plancoulaine, Sabine; Pïcard, Capucine; Rozenberg, Flore; Tardieu, Marc; Lebon, Pierre; Jouanguy, Emmanuelle; Rezaei, Nima; Seya, Tsukasa; Matsumoto, Misako; Chaussabel, Damien; Puel, Anne; Zhang, Shen-Ying; Abel, Laurent; Al‐Muhsen, Saleh; Casanova, Jean‐Laurent

doi:10.1172/jci59259

Cited by 269 publications

(242 citation statements)

References 50 publications

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“…These findings were supported by subsequent analysis of patients with defects in genes encoding the TLR3 signalling components TRIF, TBK-1 and IRF3 [35][36][37]. An impaired TLR3-inducible type-1 IFN response to HSV-1 in neurons and oligodendrocytes in the central nervous system (CNS) was subsequently linked with this condition [32][33][34][35][36][37]. These findings are also consistent with studies in mouse models of DNA virus infections.…”

Section: Role Of Tlr3 In Host Defencesupporting

confidence: 66%

The toll-like receptor 3 pathway in homeostasis, responses to injury and wound repair

Ramnath

Powell

Scholz

et al. 2017

Seminars in Cell & Developmental Biology

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In addition to their established roles in host defence, Tolllike Receptors (TLRs) have emerging roles in control of homeostasis, injury and wound repair. The dsRNA-sensing receptor, TLR3, has been particularly implicated in such processes in several different tissues including the skin, intestine and liver, as well as in the control of reparative mechanisms in the brain, heart and kidneys, following ischemia reperfusion injury. In this review, we provide an overview of TLR3 signalling and functions in inflammation, tissue damage and repair processes, as well as therapeutic opportunities that may arise in the future from knowledge of such pathways.

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Section: Role Of Tlr3 In Host Defencesupporting

confidence: 66%

The toll-like receptor 3 pathway in homeostasis, responses to injury and wound repair

Ramnath

Powell

Scholz

et al. 2017

Seminars in Cell & Developmental Biology

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“…Furthermore the proband (V:3) experienced primary HSV infection as gingivostomatitis, whereas one of the STAT1-deficient individuals described by Dupuis et al died of HSV encephalitis (12), and severe susceptibility to herpesviral disease appears general in complete STAT1 deficiency (13). HSV encephalitis susceptibility in humans has also been linked to mutations that specifically impair viral IFN induction (26)(27)(28)(29). The fact that herpesvirus disease severity appears relatively normal in STAT2 deficiency implies that loss of ISGF3-dependent signaling is unlikely to represent the sole mechanism for herpesviral susceptibility in these disorders.…”

Section: Resultsmentioning

confidence: 99%

STAT2 deficiency and susceptibility to viral illness in humans

Hambleton

Goodbourn

Young

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Severe infectious disease in children may be a manifestation of primary immunodeficiency. These genetic disorders represent important experiments of nature with the capacity to elucidate nonredundant mechanisms of human immunity. We hypothesized that a primary defect of innate antiviral immunity was responsible for unusually severe viral illness in two siblings; the proband developed disseminated vaccine strain measles following routine immunization, whereas an infant brother died after a 2-d febrile illness from an unknown viral infection. Patient fibroblasts were indeed abnormally permissive for viral replication in vitro, associated with profound failure of type I IFN signaling and absence of STAT2 protein. Sequencing of genomic DNA and RNA revealed a homozygous mutation in intron 4 of STAT2 that prevented correct splicing in patient cells. Subsequently, other family members were identified with the same genetic lesion. Despite documented infection by known viral pathogens, some of which have been more severe than normal, surviving STAT2-deficient individuals have remained generally healthy, with no obvious defects in their adaptive immunity or developmental abnormalities. These findings imply that type I IFN signaling [through interferon-stimulated gene factor 3 (ISGF3)] is surprisingly not essential for host defense against the majority of common childhood viral infections.measles vaccine | viruses | rare diseases

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“…This finding led us to hypothesize that HSE in otherwise healthy children might be caused by inborn errors of antiviral IFN-α/β immunity. We analyzed genome-wide linkage data and both blood and fibroblastic responses to herpes simplex virus and various viral intermediates in children with isolated HSE from this IFN-α/β-based angle, and we discovered mutations affecting five genes governing the TLR3-mediated IFN-α/β pathway (116)(117)(118)(119)(120)(121). Another group recently identified a mutation in a sixth gene (122).…”

Section: Hse: a Genetic Diseasementioning

confidence: 99%

Severe infectious diseases of childhood as monogenic inborn errors of immunity

Casanova

2015

Proc. Natl. Acad. Sci. U.S.A.

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202

163

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This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.

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Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency

Cited by 269 publications

References 50 publications

The toll-like receptor 3 pathway in homeostasis, responses to injury and wound repair

The toll-like receptor 3 pathway in homeostasis, responses to injury and wound repair

STAT2 deficiency and susceptibility to viral illness in humans

Severe infectious diseases of childhood as monogenic inborn errors of immunity

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