Document text
Principal Investigator: Chien-Ting Wu
Organization: UT SOUTHWESTERN MEDICAL CENTER
Fiscal Year: 2024
Award: $499,989
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Human respiratory tissues have a unique cellular architecture and a mucus-based clearance system that,
together, constitute an impressive barrier to viruses that use the airway epithelium as their portal of entry. The
mucus-based clearance system acts as a physical, innate defense mechanism. Nasal epithelial cells have two
classes of protrusions on their surfaces—long motile cilia and short microvilli. Motile cilia are specialized
organelles that extend from the cell into the airway to drive mucociliary clearance. However, the mechanisms
used by respiratory viruses to breach this barrier and infect the respiratory epithelium are not well understood.
Our previous work has highlighted the crucial role of cilia in respiratory virus infection. Using cultured human
primary nasal epithelial cells, we have demonstrated that SARS-CoV-2 and RSV specifically attach to motile cilia
during infection. Importantly, inhibiting the interaction between SARS-CoV-2 or RSV and cilia can effectively
suppress viral infections, indicating the critical role of the virus-cilia interaction. Furthermore, treatment with an
inhibitor of ciliary protein trafficking significantly decreased SARS-CoV-2 infection in nasal epithelial cells. These
findings underscore the critical role of cilia during viral entry. Based on these findings, we propose specific aims
to understand how RSV and SARS-CoV-2 hijack nasal cilia for viral entry using the primary nasal epithelium as
a model. By comparing the infection mechanisms of RSV and SARS-CoV-2, we aim to gain a clearer
understanding of the differences between these viruses and the significance of nasal cilia in their respective
contexts.
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