Raphaelle Klitting, Mathilde Gondard, Laura Pezzi, Camille Victoire Migné, Rachel Bellone, Grégory L’Ambert, Teheipuaura Helle, Antoine Mignotte, Raquel Gutiérrez-Climente, Guillaume Lacour, Julien Mocq, Nazli Ayhan, Federico Lucchese, Géraldine Piorkowski, Marine Dumarest, Rayane Amaral, Karine Bolloré, Jeanne Hanin, Olivier Courot, Edouard Hirchaud, Véronique Béven, Yannick Blanchard, Anaïs Karch, Georges Jakerian, Guillaume André Durand, Gilda Grard, N. Herbreteau, A. Duvignaud, Serafín Gutiérrez, L. Aubert, Arnaud Cannet, Marion Parisey, Yannick Simonin, Malvy Denis, M. Paty, Nelly Fournet, F. Franke, Syria Laperche, Pierre Gallian, Anna-Bella Failloux, Xavier de Lamballerie, Albin Fontaine, Gaëlle Gonzalez
Importance: West Nile virus (WNV), a mosquito-borne orthoflavivirus, represents an increasing public health threat in Europe. In July 2025, WNV lineage 2 (WNV-L2) was associated with the first autochthonous cases ever detected in the metropolitan area around Paris, France; understanding the dispersal dynamics and geographic origin of these emergence events is critical for public health preparedness. Objectives: To characterize the spatial and temporal dynamics of WNV circulation in France from 2022 to 2025 and to determine the origin of the virus lineages responsible for the 2025 emergence in the Paris metropolitan area. Design, Setting, and Participants: This study was a genomic epidemiology assessment combining human, veterinary, and entomological monitoring, with viral genome sequencing and time-resolved, bayesian phylogenetic analysis. Surveillance was conducted across metropolitan France, with a focus on areas with documented WNV circulation (Eastern and Western Mediterranean, South Atlantic, and Paris). Surveillance included patients with confirmed WNV infection, avian and equine cases, and mosquito collections. Exposures: Natural exposure to WNV through mosquito vectors in affected areas. Main Outcomes and Measures: Phylogenetic relationships between emergence events across regions in France were inferred using a bayesian approach. Results: Genomic data from this epidemiological assessment encompassed 52 WNV-positive samples (6 human, 21 veterinary, and 25 entomological samples). WNV-L2 was the only lineage detected in France between 2022 and 2025. In 2024, Western Mediterranean strains were closely related to those from 2023 from the French South Atlantic area, suggesting west-to-south introduction, whereas Eastern Mediterranean strains represented genetically distinct clades associated with Northern Italy. The phylogenetic analysis of 2025 WNV sequences from the Paris area revealed that the outbreak virus strains all grouped together and originated from the L2 clade of sequences from the South Atlantic area in the 2023 to 2024 period. Conclusions and Relevance: In this study, genomic data from an epidemiologic assessment of 52 WNV-positive samples highlight the combined influence of local virus maintenance and long-distance dispersal in shaping WNV circulation in France. Strengthened genomic surveillance across ecological and administrative boundaries would be essential to anticipate further viral spread, inform response strategies, and protect populations at risk.