FROM STRUCTURE TO STRATEGY: MAPPING MAYARO VIRUS CAPSID INTERACTIONS TO REVEAL MOLECULAR MECHANISMS

Mayaro virus (MAYV), an emerging arbovirus of Togaviridae family, is endemic in Latin America. Responsible for febrile illness often followed by long-lasting arthralgia. In severe cases, MAYV infection can lead to complications such as myocarditis and neurological manifestations. Despite its impact, fundamental aspects of MAYV biology remail unclear, particularly the protein-protein interactions (PPIs) that drive viral replication. In this study, we investigate the viral capsid protein, a key factor in viral particle assembly and one of the most conserved components among alphaviruses, with special emphasis on its N-terminal region. While the external structure of MAYV is well described, little is known about the internal organization of the capsid and its interface with host factors. To address this gap, we performed affinity purification coupled with mass spectrometry (AP-MS) which revealed 123 host proteins interacting with capsid. These proteins are mainly linked to RNA metabolism, nucleocytoplasmic transport, and stress responses pathways. To validate these associations, we are employing FLAG-tagged infectious clones for immunoprecipitation under native conditions. Combining functional proteomics with structural approaches rooted in biophysics, this work provides new insights into molecular organization of the MAYV capsid and its interactions with host cell machinery. These findings contribute to a broader understanding of alphavirus assembly and replication mechanisms and may support future investigations into other neglected arboviruses.