Nature excerpt: Similarities to LL MoA? No CCR5? Drugs blocking inflammasomes? Fcγ recepto? Discuss.
The team also found that giving the mice drugs that blocked inflammasomes prevented severe respiratory distress. The drugs “rescued the mice so they were not as sick”, says Sefik. This suggests that infected macrophages have a role in the pneumonia observed in people with severe COVID-19.
The macrophages’ inflammatory response could be their way of stopping SARS-CoV-2 from replicating, says study co-author Richard Flavell, an immunologist, also at Yale, and the Howard Hughes Medical Institute. When inflammasomes were activated, the virus stopped replicating in the cells. But when the researchers blocked inflammasomes, the macrophages started producing infectious virus particles.
That is a “startling” finding, says Peiris, because it shows that macrophages can assist infection.
But Stanley Perlman, a virologist also at the University of Iowa, says follow-up studies will be needed to work out how important infected immune cells are in inducing severe COVID-19 compared with other possible mechanisms.
Viral entry
Both teams were also able to show how SARS-CoV-2 can enter immune cells. Researchers have been puzzled over this because the cells don’t carry many ACE2 receptors, the virus’s main entry point.
In experiments with human and mouse cells, Sefik and Flavell found that SARS-CoV-2 could get into lung macrophages through the limited number of ACE2 receptors present. But the virus was also sneaking in through another surface protein, known as the Fcγ receptor, with the help of antibodies. When the virus encountered antibodies attached to the Fcy receptor, instead of the virus being disabled, it got scooped up into the cell.
The team also found that giving the mice drugs that blocked inflammasomes prevented severe respiratory distress. The drugs “rescued the mice so they were not as sick”, says Sefik. This suggests that infected macrophages have a role in the pneumonia observed in people with severe COVID-19.
The macrophages’ inflammatory response could be their way of stopping SARS-CoV-2 from replicating, says study co-author Richard Flavell, an immunologist, also at Yale, and the Howard Hughes Medical Institute. When inflammasomes were activated, the virus stopped replicating in the cells. But when the researchers blocked inflammasomes, the macrophages started producing infectious virus particles.
That is a “startling” finding, says Peiris, because it shows that macrophages can assist infection.
But Stanley Perlman, a virologist also at the University of Iowa, says follow-up studies will be needed to work out how important infected immune cells are in inducing severe COVID-19 compared with other possible mechanisms.
Viral entry
Both teams were also able to show how SARS-CoV-2 can enter immune cells. Researchers have been puzzled over this because the cells don’t carry many ACE2 receptors, the virus’s main entry point.
In experiments with human and mouse cells, Sefik and Flavell found that SARS-CoV-2 could get into lung macrophages through the limited number of ACE2 receptors present. But the virus was also sneaking in through another surface protein, known as the Fcγ receptor, with the help of antibodies. When the virus encountered antibodies attached to the Fcy receptor, instead of the virus being disabled, it got scooped up into the cell.
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