Single-cell RNA Sequencing reveals impaired antiviral responses following PFOA exposure during acute viral infection 3143

Description Per- and polyfluoroalkyl substances (PFAS) exposure through contaminated drinking water is a serious environmental concern, linked to increased susceptibility to infections and adverse health outcomes. Here, we investigated the impact of perfluorooctanoic acid (PFOA) on the immune response during acute viral infection. C57BL/6 (B6) mice were exposed to PFOA via oral gavage for 2 weeks, and subsequently infected with lymphocytic choriomeningitis virus (LCMV) Cl13. Intracellular flow cytometry analysis of splenic T cells revealed that PFOA exposure significantly impaired multi-functional antiviral T cell responses, as evident from reduction in virus-specific CD8+ T cells and cytokines (IFN-γ and TNF-α). This compromised immune function was accompanied by elevated serum levels of ALT and ALP, suggesting exacerbation of LCMV-induced liver injury due to PFOA exposure. Notably, PFOA-treated mice exhibited a dramatic increase in viral load in the liver. Single-cell RNA sequencing of splenocytes highlighted impaired anti-viral signaling pathways (IFN-γ, TNF-α, IL-6/JAK/STAT3 signaling) in CD8+ effector T cells and plasma cells. Overall, our findings provide evidence that PFAS exposure disrupts antiviral immunity, leading to impaired viral clearance and exacerbated tissue damage during acute infection. These results underscore the urgent need for addressing PFAS contamination as a significant risk factor for increased severity of viral infections in exposed populations.