11/10/2021 22:02 How a rampant coronavirus variant blunts our immune defences

NEWS 09 June 2021 Correction 16 June 2021

How a rampant coronavirus variant

blunts our immune defences
The rapid spread of the B.1.1.7 variant — also called Alpha — might be linked to its
ability to dampen the body’s initial immune response.

Smriti Mallapaty

Widespread lung damage (green; artificially coloured computed tomography scan) indicates
pneumonia in a person with COVID-19. Credit: Vsevolod Zviryk/SPL

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11/10/2021 22:02 How a rampant coronavirus variant blunts our immune defences

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.

RELATED
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

What’s the risk of dying from
a fast-spreading COVID-19 human airway produced interferon, an immune
variant?
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.

Meddling 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 dampens the body’s

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11/10/2021 22:02 How a rampant coronavirus variant blunts our immune defences

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?”

doi: https://doi.org/10.1038/d41586-021-01540-8

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.

References

1. Thorne, L. G. et al. Preprint at bioRxiv

https://doi.org/10.1101/2021.06.06.446826 (2021).
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11/10/2021 22:02 How a rampant coronavirus variant blunts our immune defences

2. Parker, M. D. et al. Preprint at bioRxiv

https://doi.org/10.1101/2021.03.02.433156 (2021).

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