Graduate student Baylor Col. of Med., United States
Disclosure(s):
Hanning Li, BS: No financial relationships to disclose
Introduction/Rationale: Respiratory syncytial virus (RSV) infects nearly all children by two years of age and causes up to 199,000 childhood deaths annually worldwide. A hallmark of RSV infection is its ability to cause recurrent disease throughout life, suggesting inadequate long-term cellular immunity. Current understanding of RSV-induced immune responses is largely derived from murine models, which are only semi-permissive to infection and resistant to reinfection, limiting their translational relevance. Although RSV has been shown to infect B cells and monocytes in mice, the full extent of RSV’s interaction with diverse human immune cell subsets remains unclear.
Methods: To address this gap, we are using human peripheral blood mononuclear cells (PBMCs) to define how T cells, B cells, monocytes, dendritic cells, and natural killer (NK) cells respond to RSV infection. We hypothesize that specific PBMC subsets become differentially infected and that their susceptibilities change over the course of infection due to cellular maturation and cytokine-driven modulation.
Results: Our data shows approximately 10% excess PBMC death during RSV infection, with 1–2% of cells identified as RSV-positive by flow cytometry. Infectious viral particles are detected predominantly within cells over a 6-day infection period. Imaging flow cytometry confirms that RSV actively infects all five immune cell subsets and induces distinct phenotypic changes. Among these, monocytes exhibit the highest susceptibility, showing markedly greater viral uptake than T cells and other subsets.
Conclusion: These findings provide the first comprehensive evidence that RSV targets multiple human immune cell populations ex vivo, leading to cell-type–specific alterations. The insights gained from this study will set the stage for developing a novel co-culture system integrating adult human nasal organoids with isolated human immune cells to establish a more physiologically relevant model for studying cell-mediated immune responses to RSV infection.
