A rapidly spreading coronavirus variant knocks off the body̵
Since it was first discovered in the UK at the end of last year, the variant B.1.1.7 – also called Alpha – has been whispered around the world to become the dominant form of SARS-CoV-2. Some studies show that Alpha’s ability to exceed previously circulating variants may stem from mutations in its peak protein that allow it to enter cells more efficiently.
But a study1 released on bioRxiv on June 7 suggests that Alpha also has tricks linked to mutations outside the spike protein. These mutations probably mean that Alpha, within hours of infecting a person, suppresses the rapid response defense that the body mounts against all attackers. By blocking this ‘innate immune response’, the virus buys itself more opportunities to infect other people.
This helps Alpha “manage or hide from innate immunity – and we think it’s important for transmission,” said Clare Jolly, a virologist at University College London who helped lead the work.
Jolly and her colleagues studied how cells of the human airway produce interferon, an immune protein that starts the body’s defenses on the arrival of a pathogen. The team found that cells infected with Alpha produce much less interferon than cells infected with previously circulating SARS-CoV-2 variants. Alpha’s suppression of interferon production helps the variant stay longer in the body.
Mixture of protein
Alpha-infected cells also had much higher levels of viral RNA encoding the protein Orf9b, and of Orf9b itself. The researchers found that Orf9b attenuates the body’s defenses by interfering with host proteins that typically activate interferon production and other genes that are important for the innate immune response.
The results have not yet been peer reviewed.
A study2 published on bioRxiv on March 4 by Silvana Gaudiera, an immunogeneticist at the University of Western Australia in Perth, and her colleagues confirm some of these findings. Gaudiera and her team analyzed viral samples from humans infected with Alpha and found significantly higher levels of RNA expression – likely representing Orf9b production – than in humans infected with previous variants.
The team attributes this overexpression to a mutation outside the spike protein in genes important for viral replication. The latest paper “highlights the importance of looking beyond the spike protein for new mutations,” says Gaudiera. These results are also not yet peer reviewed.
Nevan Krogan, a geneticist at the University of California, San Francisco who led the work on Jolly, says researchers are now expanding their analysis to other variants of concern. “This virus is super sneaky,” he says. “The question is, what other tricks does it have?”