Differential genotypic signatures of Toll-like receptor polymorphisms among dengue-chikungunya mono- and co-infected Eastern Indian patients
| Autor: | Anusri Tripathi, Siddhartha Sengupta, Saikat Mukherjee, Nemai Bhattacharya |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Microbiology (medical) Adolescent Genotype viruses 030106 microbiology India Single-nucleotide polymorphism Biology Virus Replication medicine.disease_cause Polymorphism Single Nucleotide Dengue fever Dengue Young Adult 03 medical and health sciences 0302 clinical medicine medicine Humans Genetic Predisposition to Disease 030212 general & internal medicine Chikungunya Child Toll-Like Receptors virus diseases General Medicine Middle Aged TLR8 medicine.disease Virology Infectious Diseases Viral replication Child Preschool Chikungunya Fever Female Signal peptidase complex Viral load |
| Zdroj: | European Journal of Clinical Microbiology & Infectious Diseases. 40:1369-1381 |
| ISSN: | 1435-4373 0934-9723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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