The ACE2 receptor from common vampire bat (Desmodus rotundus) and pallid bat (Antrozous pallidus) support attachment and limited infection of SARS CoV-2 viruses in cell culture

Authors: Bakre, Abhijeet; Sweeney, Ryan; Espinoza, Edna; Suarez, David; BLEHERT, DAVID - Us Geological Survey (USGS); Kapczynski, Darrell

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/28/2025
Publication Date: 3/31/2025
Citation: Bakre, A.A., Sweeney, R.P., Espinoza, E., Suarez, D.L., Blehert, D.J., Kapczynski, D.R. 2025. The ACE2 receptor from common vampire bat (Desmodus rotundus) and pallid bat (Antrozous pallidus) support attachment and limited infection of SARS CoV-2 viruses in cell culture. Virology. 17(4), 507. https://doi.org/10.3390/v17040507.
DOI: https://doi.org/10.3390/v17040507

Interpretive Summary: Bats are known to harbor and or transmit viruses that can cause diseases in humans and animals. Previously, we developed a SARS-CoV-2 infection model using a cell line expressing virus receptor genes from various animals. The model allows for prediction of an animal's susceptibility to infection that could not otherwise be tested in the laboratory. In this study, chicken cells were engineered to express the receptor genes from the common vampire bat or the pallid bat to predict whether these animals could be infected and potentially spread the SARS-CoV-2 virus or its variants. Data demonstrate that receptors from both bat species support infection and replication of the original Washington isolate and delta lineage of SARS-CoV-2 variants. Both of the bat receptors allowed infection by the lambda and omicron variant but no replication was observed over time.

Technical Abstract: During the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SC2) infection was confirmed in various animal species demonstrating a wide host range of the virus. Prior studies have shown that the ACE2 protein is the primary receptor used by the virus to gain cellular entry and begin the replication cycle. In previous studies, we demonstrate that human and various bat ACE2 proteins can be utilized by SC2 viruses for entry. Bats are a suspected natural host of SC2 because of genetic homology with other bat coronaviruses. In this work, we demonstrate that expression of ACE2 genes from the common vampire bat (CVB) (Desmodus rotundus) and the pallid bat (PB) (Antrozous pallidus), supports infection and replication of some SC2 viruses in cell culture. Two cell lines were produced, CVB-ACE2 and PB-ACE2, expressing ACE2 from these bat species along with human TMPRSS2, in a model previously established using a non-permissive chicken DF-1 cell line. Results demonstrate that the original Wuhan lineage (WA1) virus, and the Delta variant, were able to infect and replicate in either of the bat ACE2 cell lines. In contrast, the Lambda and Omicron variant viruses infected both cell lines, but viral titers did not increase following infection. Viral detection using immunofluorescence demonstrated abundant S protein staining for the WA1 and Delta variants but little signal for the Lambda and Omicron variants. These studies demonstrate that while ACE2 from CVB and PB can be utilized by SC2 viruses to gain entry for infection, later variants (Lambda and Omicron) replicate poorly in these cell lines. These observations may favor more efficient human adaption in later SC2 variants that become less fit for replication in other animal species.