Biology subjects

Comas-Garcia, M.

Publications and source records attributed to Comas-Garcia, M..

2 recordsLinked to original sources

bioRxiv2025

Multiple protein-protein interactions drive the assembly and budding of the Chikungunya virion

The assembly of enveloped viruses is a highly orchestrated process that depends on the coupling of multiple protein-protein interactions within a membrane environment. To gain mechanistic insight into this process, we use Chikungunya virus as a model system to study Alphavirus assembly, focusing on the interplay between core-spike and spike-spike interactions. We begin with coarse-grained molecular dynamics simulations to systematically explore how the symmetry of the nucleocapsid core, together with the relative strengths of spike-core and spike- spike interactions, influences budding efficiency and the emergence of icosahedral particle symmetry. Building on these computational predictions, we perform site-directed mutagenesis on Chikungunya virus 181/25 and examine the consequences for particle assembly and budding in cultured cells, as well as the impact of these mutations during in-cellulo assembly. Our results reveal that canonical core-spike interactions, while necessary, are not sufficient for successful assembly. Instead, lateral interactions among glycoproteins emerge as critical determinants of efficient budding, particle stability, and the maintenance of icosahedral symmetry. Together, these findings provide an integrated computational and experimental framework for understanding the molecular principles governing Alphavirus assembly.

biophysics↗

bioRxiv2025

Highly Conserved Core Residues Define Old-World Alphaviruses and Trace Early Evolutionary Divergence

Alphaviruses are positive-sense, single-stranded RNA viruses that assemble into striking double-icosahedral particles. During budding, their nucleocapsid core forms in the cytoplasm and adopts a T=4 icosahedral symmetry, a hallmark of Alphaviruses. Here, we combine structural and phylogenetic analyses to identify the amino acids most likely to govern capsomer formation (pentamers and hexamers) and core organization. We find that these residues are highly conserved in present-day Old-World alphaviruses but are divergent in New-World lineages. This suggests that the common ancestor of both groups likely assembled cores using the same molecular interactions seen in present-day Old-World viruses. We propose that early divergence in these interactions weakened core assembly efficiency, potentially contributing to the attenuation observed in encephalitic New-World alphaviruses. This attenuation may reflect an adaptive trade-off, in which reduced assembly efficiency lowers viral replication and virulence, supporting long-term persistence in enzootic cycles. Revealing how specific residues control capsid architecture and tracing their evolutionary history, this study provides key insights into alphavirus assembly mechanisms, opening new avenues for antiviral strategies and rational vaccine design.

evolutionary biology↗