Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection
Marziah Hashimi, Thomas A. Sebrell, Jodi F. Hedges, Deann T. Snyder, Katrina Lyon, Stephanie D. Byrum, Samuel G. Mackintosh, Dan Crowley, Michelle D. Cherne, David Skwarchuk, Amanda Robison, Barkan Sidar, Anja Kunze, Emma K. Loveday, Matthew P. Taylor, Connie B. Chang, James N. Wilking, Seth T. Walk, Tony Schountz, Mark A. Jutila, Diane Bimczok
Abstract
Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat (JFB, Artibeus jamaicensis) intestinal organoid model of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Upon infection with SARS-CoV-2, increased viral RNA and subgenomic RNA was detected, but no infectious virus was released, indicating that JFB organoids support only limited viral replication but not viral reproduction. SARS-CoV-2 replication was associated with significantly increased gene expression of type I interferons and inflammatory cytokines. Interestingly, SARS-CoV-2 also caused enhanced formation and growth of JFB organoids. Proteomics revealed an increase in inflammatory signaling, cell turnover, cell repair, and SARS-CoV-2 infection pathways. Collectively, our findings suggest that primary JFB intestinal epithelial cells mount successful antiviral interferon responses and that SARS-CoV-2 infection in JFB cells induces protective regenerative pathways.