Measles virus (MeV) is the most contagious human respiratory virus, but within natural hosts MeV infections are largely cell-associated. We recently documented how virus-elicited intercellular pores facilitate rapid MeV spread in well-differentiated primary airway epithelia from human donors. Here we seek to characterize the mechanisms that promote airway epithelium entry and rapid cell-to-cell spread. Our central hypothesis is that MeV developed cell-based strategies for both processes. In aim 1 we will characterize which myeloid cells transfer infectivity to airway epithelia, and how. In aim 2 we will identify the cytoskeletal structures and processes co-opted by MeV to promote its rapid epithelial spread. Our studies will reveal how MeV spreads more rapidly than other viruses in human airway epithelia, which accounts for its exceptional contagion efficiency.
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