RAPID: Collaborative Research: Bat goblet cells as immuno-hotspots for infection of coronavirus

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Why are bats so likely to carry coronaviruses, yet seem little affected by them? Many studies have focused on their immune system, but there is much to learn about the cells viruses attack upon entry. Acute respiratory symptoms, as well as the curious loss of the sense of smell in human patients with COVID-19 hint that cells in the nasal passage are afflicted first. Indeed, cells that produce mucus in the nose, known as goblet cells, have been shown to be “ground zero” for viral entry. Since these cells are also present in bat noses, there must be a difference in how coronaviruses attack goblet cells in bats versus humans. However, virtually nothing is known about immune-related proteins in bat goblet cells. This project proposes a new approach to understand how bats are resistant to respiratory viruses such as those related to SARS-CoV-2. By generating a multi-dimensional study of the anatomy and physiology of the upper respiratory tract —nose and pharynx— of bats, the proposed work will enable researchers to better understand how viruses enter the body and infect or fail to infect their hosts. This project will also allow health agencies around the world to better survey bat populations and prevent future pandemics similar to COVID-19. In addition, this proposal supports a graduate student and post-doctoral fellow to increase training in STEM fields. Researchers supported by this award will test the hypothesis that bats with nasal anatomy similar to humans have a specific composition of the lining of their respiratory tract, evolved to prevent viruses such as SARS-CoV-2, from infecting them. To understand how the lining, or epithelium, is modified in bats compared to humans, this grant will compare the proteins, DNA, and histology of bats to humans and mice. The proposed work will highlight the role of goblet cells, which do not only produce mucus, but also have immune and inflammatory functions, as critical for infection from- versus resistance to viral attack. The team will also integrate layers of data, from 3D imaging to proteomics, to build a complete picture of the inner and outer workings of the upper respiratory tracts of bats. By visualizing the anatomy in high resolution and uncovering which specific proteins are produced by the lining of the bat’s nasal passage, this project will produce the most thorough study of the upper respiratory tracts of bats yet. This will be critical for humanity’s fight against zoonotic viruses, and surveillance of wildlife populations. This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.