SARS-CoV-2 Receptor ACE2 Is Enriched in a Subpopulation of Mouse Tongue Epithelial Cells in Nongustatory Papillae but Not in Taste Buds or Embryonic Oral Epithelium.

As a result of the COVID-19 pandemic, evidence revealed that SARS-CoV-2 infection caused taste loss at a rate higher than that of influenza. ACE2, the entry receptor of SARS-CoV-2, has been identified in the oral epithelium; however, it is unclear at what developmental stage ACE2 expression emerges and whether ACE2 is expressed in taste buds. To identify the specific developmental stage, we analyzed RNA-Seq data from embryonic and newborn mouse oral tissue. We found that robust ACE2 expression was observed in the newborn oral epithelium. In contrast, only extremely low levels, if any, of ACE2 transcripts in the embryonic stage oral tissue were found (E12.5 and E14.5). Analyses of three public scRNA-seq data sets of adult mouse tongue epithelial cells showed that receptors for various viruses were enriched in distinct clusters of tongue epithelial cells. ACE2 was enriched in a subpopulation of epithelial cells in the basal region of nongustatory filiform papillae but not in the taste papillae or taste buds. Expression of ACE2 was detected in a small proportion of type III taste cells. Our results indicate that when applied across species, nongustatory papilla epithelial cells are the prime targets for SARS-CoV-2 infection in the tongue; thus, taste loss in COVID-19 patients is likely not caused by a direct infection of SARS-CoV-2 to taste bud cells. Additionally, fetuses at different stages of development may have distinct susceptibility to SARS-CoV-2 infection.