RE: ACE 2 receptors CEO comment27 Apr 2020 15:49
Dear Andrew,
The finding that ACE2 mRNA expression is increased in lung epithelial cells by interferons (IFNs) is interesting although the impact of this finding in the context of SARS CoV2 infection remains to be determined. The following points need to be considered:
It was found that the effect of IFN? on ACE2 expression was greater than that of IFN? or IFN?, so not all interferons are equal in this respect.
• While it might be argued that more ACE2 could enhance infection, the ability of type I IFNs to induce an anti-viral programme in parallel with this effect should actually prepare the cells to respond better to the infection and enhance their ability to fight off the virus.
• The data in the paper are predominantly for ACE2 mRNA expression, not ACE2 protein expression – these do not always reflect each other.
Thus, while Supplemental Fig 5M shows a western blot for the induction of ACE2 protein by IFN???there is no clear upregulation of the protein.
However, there is the possibility that ACE2 was shed from the cell surface after up-regulation in response to IFN treatment. While this was not investigated, if it did occur, it would provide additional protection as the sACE2 would ‘mop up’ the virus before it can infect the cells.
• ACE2 has anti-inflammatory roles (either as a membrane bound or soluble protein), so upregulation may be beneficial by countering the inflammation caused by the virus. As discussed in the paper, this is clearly shown in murine models of influenza infection where knock out of ACE2 results in increased lung pathology and increased mortality.
I hope you find these points to be of interest especially in the context of the use of inhaled IFN-beta1 for treatment of SARS CoV2. If you have any further queries, please don’t hesitate to contact me.
Kind regards,
Richard
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