However, in co-culture conditions in which ACE2 and TMPRSS2 are expressed in acceptor cells and S-protein in donor cells, we concluded that both Furin (in the TGN) and TMPRSS2 (at the cell surface) cleave S-protein into S1/S2 and S2′ in the presence of ACE2 (submitted), but that in addition TMPRSS2 can also process and shed ACE2 into a soluble form thereby modulating viral entry and infection. The gene discussed is ACE2; the disease is infection.