Ultraviolet exposure conditions skin to enhance arbovirus infection and mosquito probing

Abstract Mosquito-borne viruses are inoculated into skin, yet how environmental exposures shape susceptibility remains unclear. We identify ultraviolet (UV) exposure as an unrecognised determinant of mosquito-borne virus infection. In mice, prior UV exposure increased Semliki Forest virus replication, viraemia and mortality, and also enhanced Zika virus infection. Early susceptibility was driven by recruited CCR2-dependent myeloid cells that were preferentially infected and amplified virus. This phase was transient: by one week, infection shifted toward proliferating fibroblasts within repairing skin, accompanied by a glycolytic tissue signature. In primary human dermal fibroblasts, viral replication was governed by metabolic state rather than proliferation alone, suggesting that repair-associated metabolic reprogramming underlies stromal permissiveness. Topical steroids partially alleviated UV-conditioned enhancement of virus susceptibility. UV also warmed skin and increased mosquito probing. Together, these findings establish UV exposure as a driver of conditioned states that determine arbovirus susceptibility, identifying sunlight as a modifiable determinant of vector-borne disease risk. In Brief / eTOC blurb McCafferty-Brown et al. show that ultraviolet exposure conditions skin to enhance mosquito-borne virus infection. Susceptibility shifts from infected myeloid cells early after UV to proliferating fibroblasts with a glycolytic tissue signature during repair, while UV-exposed skin also increases Aedes aegypti probing.