P35 Ultraviolet radiation remodels the skin to increase susceptibility to mosquito-borne virus infection
Ailish McCafferty-Brown, Yonca Keskek Turk, Andrew Durham, Kosar Babani, Abd Alhadi Abou Swid, Amani M Alhazmi, Lewis Kajtar, Daniella A Lefteri, Steven R Bryden, Kave Shams, Clive McKimmieAbstract
Introduction and aims
The skin is the essential first site of infection for all mosquito-borne viruses. Events occurring in the skin immediately after mosquito transmission critically shape viral replication and disease outcome. Environmental factors that modify cutaneous immunity therefore have the potential to alter host susceptibility to infection. Ultraviolet (UV) radiation is a common and clinically relevant skin stressor that induces inflammation and tissue remodelling, yet its impact on arbovirus infection is poorly understood. The aim of this study was to determine how prior UV exposure alters the cutaneous immune environment to influence arbovirus susceptibility, and to define the cellular mechanisms and UV wavelengths (UVA vs. UVB) responsible.
Methods
We used an immunocompetent mouse model of arbovirus infection incorporating transmission by Aedes aegypti mosquito bite. Mice were exposed to erythemal or nonerythemal doses of UV radiation prior to infection. Skin immune responses were assessed by flow cytometry, histology and gene expression analysis. Myeloid cell recruitment was manipulated using depletion approaches. Stromal fibroblast proliferation was assessed in vivo, and complementary in vitro infections were performed using primary mouse skin fibroblasts under proliferative or quiescent conditions. Ongoing studies directly compare UVA and UVB exposure.
Results
Prior UV exposure significantly enhanced arbovirus infection in the skin for several weeks. UV rapidly induced chemokine expression and leucocyte infiltration. By 1 week post-UV exposure, the virus targeted proliferating skin fibroblasts. Preliminary in vitro data indicate that replicating fibroblasts are more permissive to viral infection than nondividing cells.
Conclusions
UV-induced skin inflammation and tissue remodelling create defined windows of heightened susceptibility to mosquito-borne virus infection. These findings highlight the central role of the cutaneous immune environment in shaping early infection and identify UV exposure as a modifiable risk factor influencing arboviral disease.