How a single viral protein hijacks immune cells to supercharge COVID-19 infection

In the sickest COVID-19 patients, SARS-CoV-2 doesn't just cause severe damage by directly infecting airway cells. The virus can also trigger hyperinflammation—a cycle in which immune cells themselves become infected, stop fighting the virus and instead trigger high levels of inflammation throughout the lungs.

Now, researchers at Gladstone Institutes and UC San Francisco (UCSF) have discovered how a SARS-CoV-2 protein called ORF8 is responsible for hijacking the immune system’s macrophages and causing this dangerous cycle. The work, published in Science Advances, also shows that blocking ORF8 reduces lung inflammation and damage in mice infected with SARS-CoV-2.

“Our results reveal that ORF8 is really a key ringleader behind how SARS-CoV-2 spreads and causes severe lung inflammation,” says Melanie Ott, MD, Ph.D., the Nick and Sue Hellmann Distinguished Professor and director of the Gladstone Infectious Disease Institute. “By showing how this protein tricks our immune cells, we’ve uncovered a promising new path for developing treatments to protect the lungs.”

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