Two - faced interferon
Immunity helps coronavirus infect cells
Kirill Stasevich, Science and Life (nkj.ru )
The SARS-CoV-2 coronavirus penetrates the cell with its S protein, which is dotted with the lipid envelope of the virus. Protein S interacts with another protein that many of our cells have – the ACE2 receptor, or angiotensin converting enzyme. ACE2 helps control blood pressure, but the coronavirus has learned to use it for its own purposes: after the viral S-protein binds to ACE2, the cell membrane bends and the virus sinks into the cell. Generally speaking, other SARS-CoV-2 proteins, sitting in its shell together with S-protein, play a role here, but S and cellular ACE2 still remain the main ones.
Obviously, the more the ACE2 receptor-enzyme sits on the cell, the easier it is for the virus to penetrate it, the more viral particles will infect it. Employees of the Max Delbruck Center for Molecular Medicine, the Charite Clinic, the Free University of Berlin and other scientific centers write in an article in EMBO Molecular Medicine (Heuberger et al., Epithelial response to IFN‐γ promotes SARS‐CoV‐2 infection) that the ACE2 protein on cells may become larger due to active work immunity. When the virus appears in the body, immune cells begin to secrete gamma interferon. It is one of the main signaling proteins that stimulates the activity of immune cells and enhances the production of other signaling molecules.
It turned out that under the action of gamma interferon, mucosal cells synthesize more ACE2. That is, the immune protein helps the coronavirus enter the cells. Experiments were performed with an intestinal organoid: a microscopic likeness of the intestine formed by stem cells, which were allowed to form into a three-dimensional structure. (It is known that the new coronavirus infects not only the cells of the respiratory system, but also the cells of the intestine.) When gamma interferon was added to an organoid, the activity of the gene encoding ACE2 increased in the cells of its mucous membrane, and ACE2 itself became more. And if SARS-CoV-2 was also added to the organoid, then more coronavirus RNA appeared in the mucosal cells after interferon treatment.
It is possible that particularly severe and particularly prolonged cases of coronavirus infection are associated, among other things, with the action of gamma interferon. Whether this is true or not, you need to check in clinical studies, because it's one thing to have an organoid, and another thing is a real complex organism. But if everything turns out that way, then you can think about how to prevent interferon assistance to the coronavirus from the immune system.
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