Mapping host responses in the nasal mucosa during respiratory viral infections to identify cellular determinants of severe disease (360G-Wellcome-329701_Z_25_Z)

Respiratory viruses impose a significant burden on healthcare systems worldwide, with the greatest impact on children in low- and middle-income countries (LMICs). While previous studies, primarily in high-income settings, have characterized virally-induced mucosal cell states, their relevance in LMIC populations, where genetic diversity, environmental exposures, and nutritional factors differ, remains unknown. We aim to uncover the full spectrum of respiratory virus-induced epithelial and immune cell states in the nasal mucosa of children in Bangladesh. Our primary focus will be studying the response to Respiratory Syncytial Virus (RSV) in children under the age of two years at two sites (one community, one clinical) in Bangladesh, representing diverse demographic and environmental contexts. Using single-cell transcriptomics, cell culture models including air-liquid interface, and flow cytometry assays, we will define pathogenic cell states linked to severe disease by RSV, gradually expanding to other viruses, and investigate viral and host factors driving these states. We will also assess demographic and socioeconomic risk factors underlying severe respiratory disease in children in LMICs. This work will be a collaboration between research groups in Bangladesh and the USA and will generate critical insights into respiratory viral pathogenesis and foster capacity for cutting-edge cellular and molecular research in Bangladesh.