Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection in a Bat Gastrointestinal Organoid Model

Abstract

Abstract The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is thought to have originated in bats, since multiple viruses with a high level of genetic similarity have been identified in bats. In addition to respiratory symptoms, COVID-19 frequently involves gastrointestinal symptoms such as diarrhea and vomiting, indicating the SARS-CoV-2 can target the gastrointestinal (GI) tract. However, there is no robust in vitro model for assessing the SARS-CoV-2 infection in the bat GI tract. Here, we established gastrointestinal organoid cultures from Jamaican fruit bats (JFB),( Artibeus jamaicensis), which replicated the characteristic morphology of the gastrointestinal epithelium and showed tissue specific gene expression patterns and cell differentiation. To analyze whether JFB intestinal epithelial cells are susceptible to SARS-CoV-2, we performed in vitro infection experiments. While increased SARS-CoV-2 RNA was detected in both cell lysates and supernatants from the infected organoids after 48 h, there was no evidence of active viral replication, and no infectious virus was produced. However, the JFB distal organoids significantly upregulated anti-viral and pro-inflammatory genes in response to SARS-CoV-2. Unexpectedly, SARS-CoV-2 infected JFB organoids had a decreased incidence of apoptotic cell death. Collectively, our data suggest that primary intestinal epithelial cells from JFBs are resistant to SARS-CoV-2 infection and cell damage, likely because they are able to mount a strong antiviral interferon response.