Under the hypothesis that the expression level of the ACE2 receptor correlates with the degree of infection by the virus, we screened over 10,000 experimental conditions to identify those causing a strong up- or down-regulation of ACE2. As an example, the top up-regulating condition from the Affymetrix Human 133 Plus 2 compendium (5,738 conditions tested) is the exposure of bronchial epithelial cells to polyinosinic-polycytdidylic acid (see experimental details provided). This compound, which is structurally similar to double-stranded RNA, is a known immunostimulant used to simulate viral infections (especially RNA viruses such as SARS-CoV-2) by interacting with TLR3. This raises the question as to whether the SARS-CoV-2 virus is able to trigger the up-regulation of the ACE2 receptor, thereby increasing its own ability to infect human cells .
Figure: GENEVESTIGATOR® Perturbations plot showing a subset of conditions in which ACE2 is strongly up-regulated, with a detailed view on study HS-01166 showing its reponse to poly(I:C) in bronchial epithelial cells.