Immunological landscape of human lymph nodes during ex vivo measles virus infection

Abstract

ABSTRACTLymph nodes are the primary site of replication for measles virus (MeV). Here, we modeled MeV infection in human tonsil explants, utilizing a clinical strain of MeV that expresses GFP. We show that MeV replicates efficiently in this tissue as measured by increasing infectious virus production and GFP+ cells (>10% of tonsillar cells by day 8). Using scRNA-Seq, we identified 29 cell populations, all of which were susceptible to MeV. While T cells were the most abundant cell type in the lymphoid explants, B cells were the dominant infected population. Flow cytometry analysis revealed that the preferential infection of B cells was associated with higher CD150 expression. We found that while germinal center B cells were the largest population of infected B cells, there were no differences in susceptibility to MeV among individual B cell subsets. Among CD3+ T cells, infection in both the CD4+ and CD8+ compartments displayed bias towards antigen experienced subsets and away from naive cells, consistent with relative CD150 expression. Differential gene expression analysis revealed that the host response to MeV was dominated by the potent induction of interferon stimulated genes within both T and B cells. These data provide new insights into how MeV infection progresses in lymph nodes, a critical launching point for pathogenesis.Author SummaryMeasles virus (MeV) is a re-emerging pathogen that has dramatic disease outcomes in children. Immunological amnesia is a dangerous disease outcome that is caused by MeV infection of lymphocytes. Here, we infect human tonsil explants with a GFP-expressing clinical isolate of MeV to assess the immunological events that occur during infection of this critical site. Using single-cell RNA sequencing, we identified 29 distinct populations of tonsillar cells that are susceptible to MeV infection. Further immunophenotyping revealed a preferential infection of B cell lineages compared to T cell lineages, and that among T cells, memory cells are preferential targets of infection compared to naïve counterparts. Taken together, our data thoroughly characterize the infectious and immunological events that shape disease progression in lymph nodes and identify cellular susceptibilities to MeV infection which may be critical in the development of antivirals for MeV.CONFLICTS OF INTERESTThe authors have declared that no conflict of interest exists.