The rapidly spreading variant of coronavirus blunts the body̵
Since it was first discovered in the UK late last year, variant B.1.1.7 – also known as Alpha – has flown around the world to become the dominant form of SARS-CoV-2. Some studies have shown that Alpha’s ability to anticipate previously circulating variants may result from mutations in its thorn protein that allow it to enter cells more efficiently.
But a study1 posted on bioRxiv on June 7 suggests that Alpha also has tricks associated with mutations outside the thorn protein. These mutations probably mean that within hours of infecting a person, Alpha suppresses the rapid response that the body mounts against all invaders. By blocking this “innate immune response,” the virus buys more opportunities to infect other people.
This helps Alpha cope or hide from innate immunity – and we think that’s important for transmission, “said Claire Jolie, a virologist at University College London who led the work.
Jolie and her colleagues studied how human airway cells produce interferon, an immune protein that activates the body’s defenses when a pathogen arrives. The team found that alpha-infected cells produced far less interferon than cells infected with previously circulating variants of SARS-CoV-2. Suppression of interferon production by Alpha helps the option to stay in the body longer.
Alpha-infected cells also have much higher levels of viral RNA encoding the Orf9b protein and of Orf9b itself. The researchers found that Orf9b reduced the body’s defenses by interfering with host proteins, which usually activate the production of interferon and other genes important for the innate immune response.
The findings have not yet been reviewed.
Research2 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 people infected with alpha and found significantly higher levels of RNA expression – possibly representing Orf9b production – than in people infected with previous variants.
The team attributed this overexpression to a mutation outside the thorn protein in genes that are important for viral replication. The latest article “emphasizes the importance of looking beyond the spike protein for new mutations,” Gaudera said. These findings have not yet been reviewed.
Nevan Krogan, a geneticist at the University of California, San Francisco, who led the work with Jolie, says researchers are now expanding their analysis to other options for concern. “This virus is super mean,” he says. “The question is, what other tricks are there?”