Receptors and Cofactors That Contribute to SARS-CoV-2 Entry: Can Skin Be an Alternative Route of Entry?
Abstract
:1. Introduction
2. Mechanisms and Pathways of SARS-CoV-2 Entry into Host Cells
3. SARS-CoV-2 Primary Receptor and Cofactors
3.1. ACE2
3.1.1. Background
3.1.2. ACE2 Tissue Expression and Its Importance in SARS-CoV-2 Infection
3.2. TMPRSS2
3.2.1. Background
3.2.2. TMPRSS2 Tissue Expression and Its Importance in SARS-CoV-2 Infection
3.3. Furin
3.3.1. Background
3.3.2. Furin Tissue Expression and Its Importance in SARS-CoV-2 Infection
3.4. Cathepsin L
3.4.1. Background
3.4.2. Cathepsin L Tissue Expression and Its Importance in SARS-CoV-2 Infection
3.5. NRP1
3.5.1. Background
3.5.2. NRP1 Tissue Expression and Its Importance in SARS-CoV-2 Infection
4. SARS-CoV-2 Alternative Receptors
4.1. CD147
4.1.1. Background
4.1.2. CD147 Tissue Expression and Its Importance in SARS-CoV-2 Infection
4.2. AXL
4.2.1. Background
4.2.2. AXL Tissue Expression and Its Importance in SARS-CoV-2 Infection
4.3. KREMEN1 and ASGR1
4.3.1. Background
4.3.2. KREMEN1 and ASGR1 Tissue Expression and Its Importance in SARS-CoV-2 Infection
4.4. Additional Receptors Facilitating Virus Attachment
4.5. LRRC15, a Novel Receptor Binding SARS-CoV-2 Spike and Suppressing Viral Entry
4.5.1. Background
4.5.2. LRRC15 Tissue Expression and Its Importance in SARS-CoV-2 Infection
5. Skin as an Alternative Entry Route for SARS-CoV-2 Virus
Receptors and Cofactors | Expression in Skin | References |
---|---|---|
ACE2 | mRNA: low levels (whole skin) | https://gtexportal.org, [139,144,145,146,147,149] |
Protein: keratinocytes in the basal cell layer of epidermis, smooth muscle cells surrounding sebaceous glands, eccrine gland cells | [29,138,139,147] | |
Upregulation by IFNs, IL-33, in AD, in psoriasis | [31,40,41,42,141,150,151] | |
TMPRSS2 | mRNA: low levels (whole skin) | https://gtexportal.org, [47,139,144,145], |
Protein: sweat glands | [138,141] | |
Furin | mRNA: high levels (whole skin) | https://gtexportal.org, |
Protein: keratinocytes | [161] | |
Cathepsin L | mRNA: low levels (whole skin), higher in fibroblasts, immune cells | https://gtexportal.org, [159] |
Protein: low levels in healthy skin. Upregulation in AD, psoriasis, lupus erythematosus, cSCC | [152,153] | |
NRP1 | mRNA: intermediate levels (whole skin), high in cultured fibroblasts | https://gtexportal.org, |
Protein: keratinocytes in the suprabasal cell layer of epidermis, immune cells | [77,78] | |
CD147 | mRNA: high levels (whole skin), keratinocytes, fibroblasts, immune cells | https://gtexportal.org, [145] |
Protein: keratinocytes, fibroblasts, immune cells Upregulation by IL-22, IL-1α, TGFβ1, EGF | [157] [83,157,158] | |
AXL | mRNA: intermediate levels (whole skin), high in cultured fibroblasts | https://gtexportal.org, |
Protein: Langerhans cells, keratinocytes | [155] | |
KREMEN1 | mRNA: intermediate/high levels (whole skin), expression on keratinocytes | https://gtexportal.org, [159,160] |
Protein: epidermis | https://www.proteinatlas.org | |
ASGR1 | mRNA: low levels (whole skin) Protein: macrophages | https://gtexportal.org, [110,111] |
LRRC15 | mRNA: high expression in skin Protein: fibroblasts | https://gtexportal.org, [124,162] |
6. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Barthe, M.; Hertereau, L.; Lamghari, N.; Osman-Ponchet, H.; Braud, V.M. Receptors and Cofactors That Contribute to SARS-CoV-2 Entry: Can Skin Be an Alternative Route of Entry? Int. J. Mol. Sci. 2023, 24, 6253. https://doi.org/10.3390/ijms24076253
Barthe M, Hertereau L, Lamghari N, Osman-Ponchet H, Braud VM. Receptors and Cofactors That Contribute to SARS-CoV-2 Entry: Can Skin Be an Alternative Route of Entry? International Journal of Molecular Sciences. 2023; 24(7):6253. https://doi.org/10.3390/ijms24076253
Chicago/Turabian StyleBarthe, Manon, Leslie Hertereau, Noura Lamghari, Hanan Osman-Ponchet, and Véronique M. Braud. 2023. "Receptors and Cofactors That Contribute to SARS-CoV-2 Entry: Can Skin Be an Alternative Route of Entry?" International Journal of Molecular Sciences 24, no. 7: 6253. https://doi.org/10.3390/ijms24076253