Human outbreaks of a novel reassortant Oropouche virus in the Brazilian Amazon region.

The Brazilian western Amazon is experiencing its largest laboratory-confirmed Oropouche virus (OROV) outbreak, with more than 6,300 reported cases between 2022 and 2024. Here, we sequenced and analyzed 382 OROV genomes from human samples collected in Amazonas, Acre, Rondônia, and Roraima states, between August 2022 and February 2024, to uncover the origin and genetic evolution of OROV in the current outbreak. Genomic analyses revealed that the upsurge of OROV cases in the Brazilian Amazon coincides with spread of a novel reassortant lineage containing the M segment of viruses detected in the eastern Amazon region (2009-2018) and the L and S segments of viruses detected in Peru, Colombia, and Ecuador (2008-2021). The novel reassortant likely emerged in the Amazonas state between 2010 and 2014 and spread through long-range dispersion events during the second half of the 2010s. Phylodynamics reconstructions showed that the current OROV spread was mainly driven by short-range (< 2 km) movements consistent with the flight range of vectors. Nevertheless, a substantial proportion (22%) of long-range (> 10 km) OROV migrations were also detected, consistent with viral dispersion by humans. Our data provides a view of the unprecedented spread and evolution of OROV in Brazilian western Amazon region.