tetano
Editor, Senior Moderator
Cells
. 2023 Apr 20;12(8):1198.
doi: 10.3390/cells12081198. SARS-CoV-2 Enters Human Leydig Cells and Affects Testosterone Production In Vitro
Lu Li[SUP] 1 [/SUP], Chantal M Sottas[SUP] 1 [/SUP], Hsu-Yu Chen[SUP] 2 [/SUP], Yuchang Li[SUP] 1 [/SUP], Haoyi Cui[SUP] 1 [/SUP], Jason S Villano[SUP] 3 [/SUP], Joseph L Mankowski[SUP] 3 [/SUP], Paula M Cannon[SUP] 2 [/SUP], Vassilios Papadopoulos[SUP] 1 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a SARS-like coronavirus, continues to produce mounting infections and fatalities all over the world. Recent data point to SARS-CoV-2 viral infections in the human testis. As low testosterone levels are associated with SARS-CoV-2 viral infections in males and human Leydig cells are the main source of testosterone, we hypothesized that SARS-CoV-2 could infect human Leydig cells and impair their function. We successfully detected SARS-CoV-2 nucleocapsid in testicular Leydig cells of SARS-CoV-2-infected hamsters, providing evidence that Leydig cells can be infected with SARS-CoV-2. We then employed human Leydig-like cells (hLLCs) to show that the SARS-CoV-2 receptor angiotensin-converting enzyme 2 is highly expressed in hLLCs. Using a cell binding assay and a SARS-CoV-2 spike-pseudotyped viral vector (SARS-CoV-2 spike pseudovector), we showed that SARS-CoV-2 could enter hLLCs and increase testosterone production by hLLCs. We further combined the SARS-CoV-2 spike pseudovector system with pseudovector-based inhibition assays to show that SARS-CoV-2 enters hLLCs through pathways distinct from those of monkey kidney Vero E6 cells, a typical model used to study SARS-CoV-2 entry mechanisms. We finally revealed that neuropilin-1 and cathepsin B/L are expressed in hLLCs and human testes, raising the possibility that SARS-CoV-2 may enter hLLCs through these receptors or proteases. In conclusion, our study shows that SARS-CoV-2 can enter hLLCs through a distinct pathway and alter testosterone production.
Keywords: ACE2; Leydig cells; SARS-CoV-2; SARS-CoV-2 spike pseudovectors; TMPRSS2; cinanserin; hamster; human; spike protein; testis; testosterone.
. 2023 Apr 20;12(8):1198.
doi: 10.3390/cells12081198. SARS-CoV-2 Enters Human Leydig Cells and Affects Testosterone Production In Vitro
Lu Li[SUP] 1 [/SUP], Chantal M Sottas[SUP] 1 [/SUP], Hsu-Yu Chen[SUP] 2 [/SUP], Yuchang Li[SUP] 1 [/SUP], Haoyi Cui[SUP] 1 [/SUP], Jason S Villano[SUP] 3 [/SUP], Joseph L Mankowski[SUP] 3 [/SUP], Paula M Cannon[SUP] 2 [/SUP], Vassilios Papadopoulos[SUP] 1 [/SUP]
Affiliations
- PMID: 37190107
- DOI: 10.3390/cells12081198
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a SARS-like coronavirus, continues to produce mounting infections and fatalities all over the world. Recent data point to SARS-CoV-2 viral infections in the human testis. As low testosterone levels are associated with SARS-CoV-2 viral infections in males and human Leydig cells are the main source of testosterone, we hypothesized that SARS-CoV-2 could infect human Leydig cells and impair their function. We successfully detected SARS-CoV-2 nucleocapsid in testicular Leydig cells of SARS-CoV-2-infected hamsters, providing evidence that Leydig cells can be infected with SARS-CoV-2. We then employed human Leydig-like cells (hLLCs) to show that the SARS-CoV-2 receptor angiotensin-converting enzyme 2 is highly expressed in hLLCs. Using a cell binding assay and a SARS-CoV-2 spike-pseudotyped viral vector (SARS-CoV-2 spike pseudovector), we showed that SARS-CoV-2 could enter hLLCs and increase testosterone production by hLLCs. We further combined the SARS-CoV-2 spike pseudovector system with pseudovector-based inhibition assays to show that SARS-CoV-2 enters hLLCs through pathways distinct from those of monkey kidney Vero E6 cells, a typical model used to study SARS-CoV-2 entry mechanisms. We finally revealed that neuropilin-1 and cathepsin B/L are expressed in hLLCs and human testes, raising the possibility that SARS-CoV-2 may enter hLLCs through these receptors or proteases. In conclusion, our study shows that SARS-CoV-2 can enter hLLCs through a distinct pathway and alter testosterone production.
Keywords: ACE2; Leydig cells; SARS-CoV-2; SARS-CoV-2 spike pseudovectors; TMPRSS2; cinanserin; hamster; human; spike protein; testis; testosterone.