RAPID: Adaptive immunity in bats: foundational knowledge for assessing specific pathogen responses in natural coronavirus reservoirs

In recent years a number of infections have passed from non-human animals to humans causing numerous different diseases and creating significant burdens on public health and the economy. In particular, the current COVID-19 pandemic is caused by SARS-CoV-2, a coronavirus whose ancestors likely evolved in a non-human animal. In general, bats host a wide diversity of coronaviruses. Indeed, SARS-CoV-2, like its relative SARS-CoV, the virus that causes SARS, is hypothesized to have its origins in bat hosts. The proposed research seeks to understand how the natural hosts of viruses respond to these infections with a specific focus on bat immunity. Bats are a hugely diverse group that have been linked to numerous emerging human infections but also provide critical ecosystem services such as pest control, seed dispersal and pollination. The research will clarify how bat immunity has shaped the evolution of these viruses. This will yield insights into how to potentially prevent, manage or treat infections in people, as well as protect and better understand bats. The research will also facilitate the training of undergraduate students in genomic laboratory techniques and bioinformatic analysis, training the next generation of scientists.

Currently, there is a limited understanding of bat immunity, hampered in part by the diversity of bat species and lack of immunological reagents for studying them. In particular, most research has focused on innate immunity in a few species; almost nothing is known about the immunoglobulins and T cells that form the basis of adaptive immunity. The proposed research overcomes these obstacles by using genomic methods to understand adaptive immunity in multiple bat species. Specifically, the proposed research will 1) analyze the germline and rearranged immunoglobulin and T cell receptor repertoires in multiple, diverse bat species, including known coronavirus hosts, using a mix of gene capture, long-read sequencing, and targeted amplification and sequencing; 2) characterize the cells involved in adaptive immunity using single-cell transcriptomics; and 3) test for coronaviruses in wild bats and compare the immunoglobulin repertoire between infected and uninfected bats. The results will provide foundational knowledge of adaptive immunity of an important reservoir group, clarifying the bat-pathogen relationship in multiple species. These findings can be leveraged by others to characterize the responses of bats to specific pathogens, to predict whether certain species are better equipped to respond to infection, and to guide prevention and intervention efforts for zoonotic disease. 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.