Mutation in Covid-19 virus made variants better at escaping immunity and more infectious, says University of Cambridge’s Ravi Gupta
A key mutation seen in the Alpha variant of the Covid-19 virus enables it to replicate efficiently even when it has other changes in its make-up that might otherwise weaken it, international research has found.
The deletion of two amino acids, H69/V70, enables the virus to “have its cake and eat it”, according to University of Cambridge’s Prof Ravi Gupta, as it allows some variants to both escape immunity and be more infectious.
Mutations occur naturally in viruses as they spread. Researchers found the deletion H69/V70 has expanded globally, particularly across much of Europe, Africa and Asia, and is present in more than 600,000 SARS-CoV-2 genome sequences worldwide.
It was present in the variant that was primarily responsible for the UK’s winter lockdown.
Prof Gupta, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease, the senior author of the new study in Cell Reports, said: “Although we first saw this mutation in an immunocompromised patient and then in the Kent – now ‘Alpha’ – variant, when we looked at samples from around the world, we saw that this mutation has occurred and spread multiple times independently.
“When viruses replicate, any mutations they acquire can act as a double-edged sword: a mutation that enables the virus to evade the immune system might, for example, affect how well it is able to replicate.”
Prof Gupta and colleagues used a harmless form of the virus with the H69/V70 deletion to understand how its spike protein interacts with host cells. It is these proteins that bind to the ACE2 protein receptor on the surface of cells in our body.
“What we saw with the H69/V70 deletion was that in some cases, the deletion helped the virus compensate for the negative effects that came with other mutations which allowed the virus to escape the immune response,” said Prof Gupta.
“In other words, the deletion allowed these variants to have their cake and eat it – they were both better at escaping immunity and more infectious.”
The mutation made the virus twice as infective because it carried a greater number of mature spike proteins on its surface.
This heightened ability to break into a host’s cells meant it could replicate efficiently even when it has other mutations that might otherwise hinder it.
Dr Dalan Bailey, from The Pirbright Institute, who co-led the research, added: “In evolutionary terms, when a virus develops a weakness, it can lead to its demise, but the H69/V70 deletion means that the virus is able to mutate further than it otherwise would. This is likely to explain why these deletions are now so widespread.”
Bo Meng from the Department of Medicine at the University of Cambridge, first author on the paper, said: “Understanding the significance of key mutations is important because it enables us to predict how a new variant might behave in humans when it is first identified. This means we can implement public health and containment strategies early on.”
The research was led by scientists at the University of Cambridge, MRC-University of Glasgow Centre for Virus Research, The Pirbright Institute, MRC Laboratory of Molecular Biology in Cambridge and Vir Biotechnology.
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