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Principal Investigator: Jason Matthew Elinoff
Organization: CLINICAL CENTER
Fiscal Year: 2021
Funding agency: NIH Clinical Center
In FY21, we determined the expression levels of known and putative host viral entry molecules including angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), neuropilin 1 (NRP1), and DC-SIGNR (CD209L/CLEC4M) in primary human lung endothelial cells (ECs). Results were compared to human embryonic kidney (HEK293) cells, a cell line that is known to be permissive to SARS-CoV-2 entry. Additionally, experiments utilizing both SARS-CoV-2 pseudotyped lentiviral particles as well as live SARS-CoV-2 (WA1/2020) were conducted in various types of primary human ECs and the human Ea.hy926 endothelial line in order to determine whether human ECs were susceptible to SARS-CoV-2 infection in vitro.
The results of this work revealed that primary human pulmonary artery and lung microvascular ECs express low levels of ACE2, TMPRSS2, and CD209L but high levels of NRP1. Neither pseudotyped nor live SARS-CoV-2 virus appear to generally infect or replicate in primary human pulmonary ECs in vitro. Furthermore, overexpression of TMPRSS2 with ACE2 in HEK293 cells further increased infection with SARS-CoV-2 pseudotyped lentivirus whereas overexpression of NRP1 with ACE2 or CD209L with ACE2+TMPRSS2 appears to decrease infection compared to ACE2 overexpression alone. In conclusion, low levels of ACE2 and TMPRSS2 expression in cultured primary human lung ECs may explain their diminished susceptibility to SARS-CoV-2 infection. Future work is planned to determine whether overexpression of ACE2 and/or TMPRSS2, cell matrix, circulating factors in COVID+ patient serum or plasma, or different Spike protein variants impact human EC susceptibility to infection in vitro.
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