ACE2 is a crucial in vivo SARS-CoV receptor required for effective viral replication. SARS-CoV infection of wild-type mice resulted in reduced ACE2 expression in the lungs. Spike-Fc binding to ACE2 induced downregulation of ACE2 in cell lines. Treatment with Spike-Fc in mice enhanced acid-induced lung injury, downregulated ACE2 protein expression in lungs, and further (more than acid aspiration) increased Ang II levels. SARS-CoV spike+acid–mediated lung failure was rescued by an ARB. The gene discussed is ACE2; the disease is severe acute respiratory syndrome.