Binding Evolution of the Dengue Virus Envelope Against DC-SIGN: A Combined Approach of Phylogenetics and Molecular Dynamics Analyses Over 30 Years of Dengue Virus in Brazil

• Published in: Journal of molecular biology 2024-06, Vol.436 (11), p.168577-168577, Article 168577
• Main Authors: Penteado, André Berndt, de Oliveira Ribeiro, Geovani, Lima Araújo, Emerson Luiz, Kato, Rodrigo Bentes, de Melo Freire, Caio Cesar, de Araújo, Joselio Maria Galvão, da Luz Wallau, Gabriel, Salvato, Richard Steiner, de Jesus, Ronaldo, Bosco, Geraldine Goés, Franz, Helena Ferreira, da Silva, Pedro Eduardo Almeida, de Souza Leal, Elcio, Goulart Trossini, Gustavo Henrique, de Lima Neto, Daniel Ferreira
• Format: Article
• Language: English
• Subjects: Brazil; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Dengue - virology; dengue envelope protein; dengue virus; Dengue Virus - genetics; Dengue Virus - metabolism; Evolution, Molecular; Host-Pathogen Interactions - genetics; Humans; Lectins, C-Type - chemistry; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Molecular Dynamics Simulation; Phylogeny; Protein Binding; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Virus - chemistry; Receptors, Virus - genetics; Receptors, Virus - metabolism; Red Queen Hypothesis; Viral Envelope - metabolism; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; viral evolution; viral phylogeny
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2024.168577

[Display omitted] •The Red Queen Hypothesis in virus-host interactions; viruses adapt proteins, hosts alter receptors.•Mutual adaptation shapes receptor interactions, informing disease unpredictability and interventions.•The article utilizes phylogenetics, modeling, and dynamics, focusing on Brazilian Dengue strains.•Viral quasispecies explores mutational space elegantly,linking genotype mutations to phenotype variations.•Energetic decomposition analyses identifies critical amino acids, highlighting Phe 313 in DC-SIGN interactions. The Red Queen Hypothesis (RQH), derived from Lewis Carroll's “Through the Looking-Glass”, postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.