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European Journal of Clinical Microbiology & Infectious Diseases

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01-07-2021 | Original Article

Differential genotypic signatures of Toll-like receptor polymorphisms among dengue-chikungunya mono- and co-infected Eastern Indian patients

Authors: Siddhartha Sengupta, Saikat Mukherjee, Nemai Bhattacharya, Anusri Tripathi

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 7/2021

Abstract

Dengue (DENV) and chikungunya (CHIKV) viral infections trigger high patient morbidity and mortality. Mono-/co-infection of these viruses activates innate immune response, triggering Toll-like receptor (TLR) pathways. The present study investigated the differential role of TLR3, 7 and 8 single-nucleotide polymorphisms (SNPs) between mono- and co-infected Eastern Indian patients. Interaction of TLR polymorphic variants with signal peptidase complex (SPC18) was explored which might affect immune signalling against DENV/CHIKV infections. Out of 550 febrile symptomatic patients, 128 DENV-CHIKV co-infected samples were genotyped for eight SNPs of TLR3 (rs3775290-chr4:186083063), TLR7 (rs179008-chrX:12885540, rs5741880-chrX:12869297, rs179010-chrX:12884766, rs3853839-chrX:12889539) and TLR8 (rs5744080-chrX:12919685, rs3764879-chrX:12906578, rs3764880-chrX:12906707) by PCR-RFLP along with 157 healthy individuals. Statistical analysis established genotypic association of TLR SNPs with DENV-CHIKV co-infection, and difference between mono- and co-infected patients and their role in determining high viral load (HVL) during competitive viral replication among co-infected patients. In silico protein-protein docking evaluated interactive effect of TLR variants with SPC18. The findings revealed patients with CC genotypes of TLR7 and 8 SNPs were significantly susceptible towards co-infection, whereas specific genotypes of TLR7 and 8 imparted protection against co-infection. Differential analysis between mono-/co-infected patients revealed distinct genotypic distribution of TLR3, 7 and 8 SNPs. Co-infected patients with TT-rs179010 exhibited DENV-HVL, whereas CHIKV-HVL was detected among patients with other genotypes. Molecular docking of TLR7-rs179008 Q variant and TLR8-rs3764880 V variant with SPC18 generated better free binding energy. This study underlined the importance of TLR7 and 8 SNPs towards mono-/co-infection of DENV/CHIKV, with certain genotypes associated with co-infection susceptibility. Moreover, it suggested a probable role of specific genotypes of TLR7 and 8 polymorphisms imparting high dengue/chikungunya viral load among co-infected patients.

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Title: Differential genotypic signatures of Toll-like receptor polymorphisms among dengue-chikungunya mono- and co-infected Eastern Indian patients
Authors: Siddhartha Sengupta
Saikat Mukherjee
Nemai Bhattacharya
Anusri Tripathi
Publication date: 01-07-2021
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Clinical Microbiology & Infectious Diseases / Issue 7/2021
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI: https://doi.org/10.1007/s10096-020-04125-x

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