Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue an...

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Published inInternational journal of molecular sciences Vol. 21; no. 17; p. 6000
Main Authors Sakaguchi, Wakako, Kubota, Nobuhisa, Shimizu, Tomoko, Saruta, Juri, Fuchida, Shinya, Kawata, Akira, Yamamoto, Yuko, Sugimoto, Masahiro, Yakeishi, Mayumi, Tsukinoki, Keiichi
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LanguageEnglish
Published Switzerland MDPI AG 20.08.2020
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Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.
AbstractList The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.
Author Kawata, Akira
Kubota, Nobuhisa
Yakeishi, Mayumi
Shimizu, Tomoko
Yamamoto, Yuko
Sakaguchi, Wakako
Sugimoto, Masahiro
Fuchida, Shinya
Saruta, Juri
Tsukinoki, Keiichi
AuthorAffiliation 6 Research and Development Center for Minimally Invasive Therapies, Medical Research Institute, Tokyo Medical University, 6-1-1 Shinjuku, Tokyo 160-8402, Japan; mshrsgmt@tokyo-med.ac.jp
3 Division of Dental Sociology, Department of Disaster Medicine and Dental Sociology, Kanagawa Dental University, 82 Inaoka, Yokosuka, Kanagawa 238-0003, Japan; fuchida@kdu.ac.jp
2 Department of Highly Advanced Oral Medicine, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Yokohama, Kanagawa 221-0835, Japan; shimizu@kdu.ac.jp
5 Division of Dental Hygiene, Kanagawa Dental University Junior College, 82 Inaoka, Yokosuka, Kanagawa 238-0003, Japan; yamamoto.yuko@kdu.ac.jp
1 Division of Environmental Pathology, Department of Oral Science, Kanagawa Dental University, 82 Inaoka, Yokosuka, Kanagawa 238-0003, Japan; sakaguchi@kdu.ac.jp (W.S.); n.kubota@kdu.ac.jp (N.K.); mhori77@ykh.gr.jp (M.Y.); tsukinoki@kdu.ac.jp (K.T.)
4 Division of Histology, Embryology and Neuroanatomy, Department of Oral Science, Kanagawa Dental
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– name: 1 Division of Environmental Pathology, Department of Oral Science, Kanagawa Dental University, 82 Inaoka, Yokosuka, Kanagawa 238-0003, Japan; sakaguchi@kdu.ac.jp (W.S.); n.kubota@kdu.ac.jp (N.K.); mhori77@ykh.gr.jp (M.Y.); tsukinoki@kdu.ac.jp (K.T.)
– name: 2 Department of Highly Advanced Oral Medicine, Kanagawa Dental University, 3-31-6 Tsuruya-cho, Yokohama, Kanagawa 221-0835, Japan; shimizu@kdu.ac.jp
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  orcidid: 0000-0002-7566-3330
  surname: Saruta
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/32825469$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
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2020 by the authors. 2020
Copyright_xml – notice: 2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Issue 17
Keywords saliva
ACE2
taste cell
SARS-CoV-2
oral cavity
TMPRSS2
tongue coating
furin
Language English
License https://creativecommons.org/licenses/by/4.0
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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These authors contributed equally to this work.
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SubjectTerms Angiotensin-Converting Enzyme 2
Betacoronavirus - metabolism
Coronavirus Infections - metabolism
Coronaviruses
COVID-19
Cytoplasm
Furin - metabolism
Gingiva - metabolism
Humans
Mouth Mucosa - metabolism
Pandemics
Peptidyl-Dipeptidase A - metabolism
Pneumonia, Viral - metabolism
Proteins
Saliva - metabolism
SARS-CoV-2
Serine Endopeptidases - metabolism
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus - metabolism
Tongue - metabolism
Viral infections
Virus Internalization
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