Shams, K. | Search bioRxiv

bioRxiv2026

Ultraviolet exposure remodels skin to enhance arbovirus infection and mosquito biting behaviour

AbstractMosquito-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 blurbMcCafferty-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.

microbiology↗

bioRxiv2019

Pan-viral protection against arboviruses by targeting inoculation site-based skin macrophages

Arthropod-borne viruses (arboviruses) are important human pathogens for which there are no specific antiviral medicines. The large number of genetically-distinct arbovirus species, coupled with the unpredictable nature of their outbreaks, has made developing virus-specific anti-viral medicines challenging. Instead, we have defined and targeted a key aspect of the host innate immune response to virus at the arthropod bite that is common to all arbovirus infections, potentially circumventing the need for virus-specific therapies at this site. Using mouse models and human skin explants, we identify innate immune responses by dermal macrophages in the skin as a key determinant of disease severity. Post-exposure treatment of the inoculation site by a topical innate immune agonist significantly suppressed both the local and subsequent systemic course of infection and improved clinical outcome in mice to infection with a variety of arboviruses from the Alphavirus, Flavivirus and Orthobunyavirus genuses. In the absence of treatment, anti-viral interferon expression to virus in the skin was restricted to dermal dendritic cells. In contrast, targeting the more populous skin-resident macrophages with an immune agonist elicited protective responses in key cellular targets of virus that otherwise replicated virus to high levels. By defining and targeting a key aspect of the innate immune response to virus at the mosquito bite site, we have shown that it is possible to improve outcome to infection by targeting pathways activated at the site of inoculation, and thereby identified a putative new strategy for limiting disease following infection with a variety of genetically-distinct arboviruses.\n\nOne-sentence summaryWe demonstrate that activation of innate immune responses to arbovirus at the mosquito bite is a limiting factor for preventing efficient systemic dissemination of virus and that therapeutic targeting of skin-resident macrophages can have defining inhibitory effects on the later systemic course.

immunology↗