A fast-spreading coronavirus variant blunts the body’s first line of defence, which could explain why it is more transmissible than previously circulating variants, according to a study of SARS-CoV-2 infection of cells.
Since it was first detected in the United Kingdom late last year, the variant B.1.1.7 — also called Alpha — has whizzed around the world to become the dominant form of SARS-CoV-2. Some studies show that Alpha’s ability to outstrip previously circulating variants could stem from mutations in its spike protein that allow it to enter cells more efficiently.
But a study1 posted on bioRxiv on 7 June suggests that Alpha also has tricks linked to mutations outside the spike protein. These mutations probably mean that within hours of infecting a person, Alpha suppresses the rapid-response defence that the body mounts against all invaders. By blocking this ‘innate immune response’, the virus buys itself more opportunities to infect other people.
This helps Alpha to “deal with or hide from innate immunity — and we think that is important for transmission”, says Clare Jolly, a virologist at University College London, who co-led the work.
Jolly and her colleagues examined how cells from the human airway produced interferon, an immune protein that kick-starts the body’s defences on the arrival of a pathogen. The team found that cells infected with Alpha produce much less interferon than do cells infected with previously circulating SARS-CoV-2 variants. Alpha’s suppression of interferon production helps the variant to stick around for longer in the body.
Alpha-infected cells also had much higher levels of viral RNA encoding the protein Orf9b, and of Orf9b itself. The researchers found that Orf9b dampens the body’s defences by meddling with host proteins that typically activate interferon production and other genes important for the innate immune response.
The findings have not yet been peer reviewed.
A study2 posted on bioRxiv on 4 March corroborates some of these findings. Researchers analysed viral samples from people infected with Alpha and found significantly higher levels of RNA expression — probably representing Orf9b production — than in people infected with previous variants.
The authors attribute this over-expression to a mutation outside the spike protein, in genes that are important for viral replication. The latest paper “highlights the importance of looking beyond the spike protein for new mutations”, says study co-author Silvana Gaudieri, an immunogeneticist at the University of Western Australia in Perth. These findings have not yet been peer reviewed, either.
Nevan Krogan, a geneticist at the University of California, San Francisco, who co-led the work with Jolly, says the researchers are now extending their analysis to other variants of concern. “This virus is super sneaky,” he says. “The question is, what other tricks does it have?”
Updates & Corrections
Correction 16 June 2021: An earlier version of this article misspelt Silvana Gaudieri’s surname. This has now been corrected. The story has also been amended to make clear that Gaudieri is not the lead author of a paper, but one of multiple authors.