Phylogenomics and structural modelling feature accelerated evolution of Oropouche virus: 1955 to 2024.

A large multi-country outbreak of Oropouche virus (OROV), a segmented negative-sense RNA virus, is emerging in Latin America. By analyzing publicly available whole-genome sequences spanning 1955 to 2024, this study reveals accelerated spatiotemporal evolution of OROV, cooperatively driven by genome mutagenesis and segment reassortment. The strains responsible for the 2023-2024 outbreak are universally reassortants, but form two divergent lineages, namely the Brazil and western Amazon basin lineages. This epidemic spreading is primarily fueled by localized transmission within countries and cross-border spread. Phylogenomic analysis further suggests that the S segment of the viral genome originated in Brazil around the 1740s, underwent diversification into five distinct clusters by the 1970s, and experienced rapid proliferation during 2020-2024. In contrast, the L segment originated in Peru around the 1630s and evolved into two independent clusters by the 1850s. Divergent evolutionary pressures have driven distinct patterns of amino acid changes in viral proteins between the Brazil and the western Amazon basin lineages. These mutations are predicted to alter the protein structures and bear functional consequences for viral fitness and transmission. These findings provide critical insights into the evolutionary dynamics of OROV and underscore the necessity of genome surveillance to track the transmission pathways and spatiotemporal evolution.