Dados do Trabalho

Título

Unveiling the Evolutionary Journey of DENV in Brazil: A 30-Year Phylogenomic and Structural Biology Study on Receptor Interactions and Circulating Strains

Introdução

The Red Queen theory explains the ongoing race between RNA viruses and hosts, impacting human and animal health. Dengue virus (DENV), a mosquito-borne pathogen, evolves rapidly, hindering vaccine development. Its high mutation rate and recombination generate new variants, posing challenges for disease control and vaccine efficacy. Understanding DENV evolution is crucial for effective prevention. Interaction between DENV envelope protein domain 2 and DC-SIGN receptor on dendritic cells is vital for immune response. Insights into these interactions can guide antiviral strategies. This study combines multiple analyses to explore Brazilian DENV strains' characteristics and binding interactions over time and implications for DENV strain evolution.

Objetivo (s)

Explore the influence of the mutations on circulating lineage of DENV versus its interactions with a known receptor to all four serotypes via phylogenomics and structural biology.

Material e Métodos

We retrieved all Brazilian dengue virus sequences from the ViPR database. Phylogenetic analysis and genotyping were conducted to explore the evolutionary relationships. Structural modeling and molecular dynamics were performed to examine the interactions between the dengue virus envelope protein and the DC-SIGN receptor. Docking and MM/GBSA analyses provided insights into the binding interactions.

Resultados e Conclusão

Our study investigated Dengue serotypes' interactions with DC-SIGN. DENV1 and DENV2 exhibited distinct configurations in the ED2 domain, affecting interactions. DENV2 showed increasing negative interactions over time. Only DENV2 had an interaction between Cys74 and PHE313, indicating improved interaction. DENV4 had limited interactions. The conserved region 101WGN103 showed diverse interactions with PHE313. Conformational epitopes and selective pressure analyses revealed no significant effects. Electrostatic potential predictions supported conservation with slight changes. Certain residues played significant roles in the interaction. Single nucleotide polymorphisms affected protein-protein interactions. The relationship between genotype mutations and phenotype variations in DENV is complex. Arboviruses, like DENV, are subject to evolutionary constraints. DENV-2 cosmopolitan showed improved interactions. Further studies are needed to understand this trend and develop antiviral strategies, considering the Red Queen Hypothesis's effect on DENV evolution.

Palavras-chave

Red Queen hypothesis, molecular docking

Agradecimentos

OPAS, General-Coordination of Public Health Laboratories.