Abstract
Chikungunya virus (CHIKV) caused more than 10,000 infections in Foshan, Guangdong, in 2025. Using plasma from acute-phase patients, we successfully isolated infectious CHIKV, confirmed by focus-forming assay and transmission electron microscopy. Whole-genome sequencing revealed that all isolates belonged to the ECSA-2 sub-lineage and were closely related to strains circulating on Réunion Island in 2024-2025, carrying adaptive mutations including C:T143A, E1:A226 V, and E2:I211 T/L210Q. Based on Foshan's 2025 population (∼9.6 million), the outbreak corresponded to a cumulative incidence of ∼104 cases per 100,000 inhabitants, highlighting intense transmission. Integrated virological, genomic, and epidemiological analyses characterize the rapid expansion of a single ECSA-2 genotype and underscore the need for strengthened arbovirus and genomic surveillance in southern China.