Loss of TLR3 aggravates CHIKV replication and pathology

 due to an altered virus-specific neutralizing antibody response

Zhisheng Her, Terk-Shin Teng, Jeslin JL Tan1, Teck-Hui Teo, Yiu-Wing Kam, Fok-Moon Lum, Wendy WL Lee, Christelle Gabriel1, Rossella Melchiotti, Anand K Andiappan1, Valeria Lulla,Aleksei Lulla, Mar K Win, Angela Chow, Subhra K Biswas1, Yee-Sin Leo, Marc Lecuit, Andres Merits, Laurent Rénia & Lisa FP Ng

EMBO Molecular Medicine Vol 7 | No 1 | 2015

Speaker: Shih-Chuan Li (李世詮)                        Time: 154:0000~165:00, JuneDec 103, 20145

Commentator: Dr. Pin Ling (凌斌 博士)             Place: Room 601

Abstract:

       Chikungunya Virus, or (CHIKV) has become one ofan important emerging disease to nowadays, it doesn’t not only eaffects the people in where it is originated,the place of originplace of this virus origin from, which is Africa, but also eaffects the people worldwideof wide place over world which is ranging from the south-east Asia to the Caribbean. Till todaynow, we haven’t developed any effectivespecific anti-virus vaccine or treatment, the only way to treat  help the patients suffer from severe Chikungunya fever (CHIKF) is supportive therapy. Since CHIKV and the disease it causesChikungunya fevers caused b is becoming a majory it have been public health issue world widewild. S, the scientist had have put more effort to understand the mechanism of CHIKV pathogenesis. Toll-like receptor 3 (TLR3) is athe frontier defense mechanismline of the human immune systembody to the RNA viruses; TLR3 can senses the double stranded RNA in the cell which almost stands for the entry of RNA virus and subsequently activates the interferon (IFN) pathway downstream. From the pPrevious reports have shown, that TLR3 might play important role in protecting against CHIKV infection (1). Here the authors try to precisely figure outdepict how the TLR3 affects host immunity to against CHIKV and correlate to the pathogenesis of CHIKF. In the By the experiments the authors process showeds that TLR3 is critical in both viral clearance and disease development. Using aIn the mice model, the mice without TLR3 expression have defect in virus limitation and show more severe joint inflammation. While Tthe CD4+ T-cells wereasshould be responsible for the infiltration of neutrophil into the jointsand the followeding by inflammation, however, these cells don’t show any involvement inwith the virus control and that. In additionHowever, it’s the TLR3-expressing hematopoietic cells playscritical role in viral clearanceclearance. Furthermore;. Tthe author also showedidentify that TLR3-/- mice would havehad diminished CHIKV-specific antibody expression,. and tThe natural target of antibody againstto fight CHIKV recognized by this specific antibody is the was dominantly themight be E2 glycoproteinglycoprotein; and the domains of E2 like E2EP3 could be athepotential target strategy for of anti-CKIKV drug/vaccine development. Finally, according to the clinical reports the authors found that a single nuclear polymorphism (SNP) of human TLR3 (rs6552950) could be crucial to severe CHIKF. What interesting is that pPeople carrying with the infrequent genotype GG of SNP rs6552950 would have inefficient antibody againstto CHIKV. According to discover of this report, we can have picture  of how TLR3 affects innate and adaptive immunity against CHIKV. In summary, this report sheds light on our understanding of the innate and adaptive immune system and how it interacts with CHIKV, identifying crucial information on TLR3 and potential targeting candidates.

Reference:

1.     Rudd PA, Wilson J, Gardner J, Larcher T, Babarit C, Le TT, Anraku I, Kumagai Y, Loo YM, Gale M et al (2012) Interferon response factors 3 and 7 protect against Chikungunya virus hemorrhagic fever and shock. J Virol 86: 9888 – 9898