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Human Type II Taste Cells Express Angiotensin-Converting Enzyme 2 and Are Infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

ABSTRACT: Chemosensory changes are well-reported symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The virus targets cells for entry by binding of its spike protein to cell-surface angiotensin-converting enzyme 2 (ACE2). It is not known whether ACE2 is expressed on taste receptor cells (TRCs), or whether TRCs are infected directly. in situ hybridization probe and an antibody specific to ACE2 indicated presence of ACE2 on a subpopulation of TRCs (namely, type II cells in taste buds in taste papillae). Fungiform papillae of a SARS-CoV-2⁺ patient exhibiting symptoms of coronavirus disease 2019 (COVID-19), including taste changes, were biopsied. Presence of replicating SARS-CoV-2 in type II cells was verified by in situ hybridization. Therefore, taste type II cells provide a potential portal for viral entry that predicts vulnerabilities to SARS-CoV-2 in the oral cavity. The continuity and cell turnover of a patient's fungiform papillae taste stem cell layer were disrupted during infection and had not completely recovered 6 weeks after symptom onset. Another patient experiencing post-COVID-19 taste disturbances also had disrupted stem cells. These results demonstrate the possibility that novel and sudden taste changes, frequently reported in COVID-19, may be the result of direct infection of taste papillae by SARS-CoV-2. This may result in impaired taste receptor stem cell activity and suggest that further work is needed to understand the acute and postacute dynamics of viral kinetics in the human taste bud.

SUBMITTER: Doyle ME

PROVIDER: S-EPMC8179718 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo study messenger ribonucleic acid (mRNA) and protein expressions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptors (angiotensin 1-converting enzyme 2 [ACE2] and CD147) and proteases (transmembrane serine protease 2 [TMPRSS2] and cathepsin L [CTSL]) in human oocytes, embryos, and cumulus (CCs) and granulosa cells (GCs).DesignResearch study.SettingClinical in vitro fertilization (IVF) treatment center.PatientsPatients undergoing IVF were treated at the Colorado Center for Reproductive Medicine.InterventionsOocytes (germinal vesicle and metaphase II [MII]) and embryos (1-cell [1C] and blastocyst [BL]) were donated for research at the disposition by the patients undergoing IVF. Follicular cells (CC and GC) were collected from women undergoing egg retrieval after ovarian stimulation without an ovulatory trigger for in vitro maturation/IVF treatment cycles.Main outcome measuresPresence or absence of ACE2, CD147, TMPRSS2, and CTSL mRNAs detected using quantitative reverse transcription polymerase chain reaction and proteins detected using capillary Western blotting in human oocytes, embryos, and ovarian follicular cells.ResultsThe quantitative reverse transcription polymerase chain reaction analysis revealed high abundance of ACE2 gene transcripts in germinal vesicle and MII oocytes than in CC, GC, and BL. ACE2 protein was present only in the MII oocytes, and 1C and BL embryos, but other ACE2 protein variants were observed in all the samples. TMPRSS2 protein was present in all the samples, whereas mRNA was observed only in the BL stage. All the samples were positive for CD147 and CTSL mRNA expressions. However, CCs and GCs were the only samples that showed coexpression of both CD147 and CTSL proteins in low abundance.ConclusionsCCs and GCs are the least susceptible to SARS-CoV-2 infection because of lack of the required combination of receptors and proteases (ACE2/TMPRSS2 or CD147/CTSL) in high abundance. The coexpression of ACE2 and TMPRSS2 proteins in the MII oocytes, zygotes, and BLs demonstrated that these gametes and embryos have the cellular machinery required and, thus, are potentially susceptible to SARS-CoV-2 infection if exposed to the virus. However, we do not know whether the infection occurs in vivo or in vitro in an assisted reproductive technology setting yet.

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Human Type II Taste Cells Express Angiotensin-Converting Enzyme 2 and Are Infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

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