Résumé
The distribution of receptors and cellular factors across tissues determines differential susceptibility of cells to viral infection. For SARS-CoV-2, viral spike and nucleocapsid proteins have been detected in the skin of infected patients. Whether the virus can directly infect skin cells has yet to be fully evaluated. SARS-CoV-2 enters cells via two routes: ACE2-driven endocytosis and TMPRSS2–mediated plasma membrane fusion, or ACE2/alternative receptors-driven endocytosis and cathepsin L–dependent fusion.
This study assessed the gene and protein expression of these entry receptors and co-receptors in primary keratinocytes and fibroblasts. We found that the main SARS-CoV-2 receptor ACE2 is present in human keratinocytes and is upregulated during their differentiation and TLR3-mediated activation, while the co-receptor TMPRSS2 for fusion is absent but mature cathepsin L is expressed. In vitro infection assays using the SARS-CoV-2 Delta variant showed that the virus can bind to the cell surface but cannot replicate within the cells.
These findings suggest that although active viral replication in keratinocytes is unlikely, the presence and inducible upregulation of ACE2 in response to inflammatory stimuli may confer a limited potential for cutaneous viral entry, warranting further investigation into the consequences in terms of local inflammation and viral transmission.