Defective TLR3 does not bind viral dsRNA

Stable Identifier
Reaction [transition]
Homo sapiens
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Toll like receptor 3 (TLR3) is one of the innate immunity sensors that can be activated by viral double-stranded RNA (dsRNA) to induce interferon (IFN) production by host cells including cells of the central nervous system (CNS) (e.g., neurons, astrocytes, oligodendrocytes, and microglial cells) (Bsibsi M et al. 2002; Jack CS et al. 2005; Farina C et al. 2005; Prehaud et al. 2005; Zhou Y et al. 2009). The defective TLR3 function is associated with a greater susceptibility to herpes simplex virus type 1 (HSV-1) encephalitis (HSE) in otherwise healthy individuals (Zhang SY et al. 2007; Guo Y et al. 2011). HSE is a rare life-threatening complication during HSV-1 infection of the CNS. TLR3 deficiency was found to be an autosomal dominant immunodeficiency caused by the heterozygous TLR3 gene mutation (P554S) reported for 2 unrelated patients or autosomal recessive immunodeficiency due to compound heterozygous mutation (P554S, E746*) in TLR3 gene reported for one patient (Zhang SY et al. 2007; Guo Y et al. 2011). The functional defect in HSE patients with TLR3 deficiency is probably due to a failure to initiate response to viral dsRNA resulting in impaired induction of type I and III interferons (IFN) by the cells of CNS (Zhang SY et al. 2007; Guo Y et al. 2011; Lafaille FG et al. 2012).
Literature References
PubMed ID Title Journal Year
17872438 TLR3 deficiency in patients with herpes simplex encephalitis

Hovnanian, A, Abel, L, Casrouge, A, von Bernuth, H, Lebon, P, Elain, G, Zhang, XX, Vallée, L, Lorenzo, L, Barreiro, L, Leonard, J, Plancoulaine, S, Quintana-Murci, L, Cognet, C, Rozenberg, F, Romero, P, Sancho-Shimizu, V, Smahi, A, Chapgier, A, Geissmann, F, Héron, B, Hamilton, C, Ku, CL, Jouanguy, E, Ugolini, S, Titeux, M, Puel, A, Picard, C, Zhang, SY, Vivier, E, Segal, D, Casanova, JL, Tardieu, M

Science 2007
21911422 Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity

Abel, L, Doireau, V, Lebon, P, Lorenzo, L, Plancoulaine, S, Alsina, L, Cardon, A, Rozenberg, F, Sancho-Shimizu, V, Azevedo, J, Ciancanelli, M, Chaussabel, D, Geissmann, F, Philippe, PB, Pérez de Diego, R, Herman, M, Jouanguy, E, Vogt, G, Andrianirina, ZZ, Picard, C, Zhang, SY, Pauwels, E, Anguiano, E, Guo, Y, Audry, M, Casanova, JL, Tardieu, M

J. Exp. Med. 2011
Normal reaction
Functional status

Loss of function of TLR3 variants [endosome membrane]

Name Identifier Synonyms
primary immunodeficiency disease DOID:612 immune deficiency disorder, immunodeficiency syndrome, hypoimmunity
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