Molecular Characterization of Rift Valley Fever Virus From the 2025 Outbreak in Northern Senegal Reveals Lineage H Persistence and Key Polymerase Mutations.

Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus that causes severe febrile and hemorrhagic illness in humans. In September 2025, an outbreak in northern Senegal led to 119 confirmed infections and 15 deaths as of October 7, 2025. We performed rapid genomic sequencing to characterize the virus responsible for this epidemic. RNA from RT-qPCR-confirmed samples was sequenced using the Twist Comprehensive Viral Research Panel on an Illumina iSeq 100 platform. Consensus genomes were analyzed with and compared with all complete RVFV genomes in GenBank. Nine genomes were recovered, including five complete tripartite sequences. All clustered within lineage H, sharing > 99% nucleotide identity with Senegalese isolates from 2020 to 2022. Alongside two conservative mutations (R137K and K1111R in S and M segments, respectively), a single nonconservative D11N substitution in the L polymerase may affect replication efficiency, while Gn and Gc epitopes remained conserved. Phylogenetic analyses confirmed strong genetic continuity with earlier West African isolates, indicating local persistence rather than reintroduction. Lineage H persistence in Senegal, combined with polymerase substitutions under purifying selection, suggests subtle viral adaptation that may affect replication. Conserved glycoprotein epitopes indicate maintained vaccine relevance. Sustained genomic surveillance integrated with clinical and ecological monitoring remains essential to anticipate viral evolution and guide Rift Valley fever control.