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Coronavirus: Researchers at the University of Pittsburgh have discovered a kind of mutation that hadn’t been seen in coronaviruses before and raises fresh concerns about the evolution of vaccine resistance.

In their search for mutations, researchers have mostly focused on flips of one genetic letter to another — a kind of mutation known as a substitution. But Paul Duprex and his colleagues discovered that the viruses mutating in a chronically infected patient were changing differently: They were losing sets of genetic letters.

Typically, a mutation that deletes a genetic letter is catastrophic to a virus. Our cells read genetic letters three at a time to choose a new building block to add to a growing protein. A deletion of one genetic letter can entirely scramble the instructions for a viral protein, so that it cannot form a functional shape.

But Dr. Duprex and his colleagues found that the coronaviruses in the patient could lose genetic letters and yet stay viable. The secret: The viruses lost genetic letters in sets of three. Instead of destroying the genetic recipe for a viral protein, the mutations snipped out one or more amino acids.

As much as Dr. Duprex despises the pandemic, he finds it hard not to admire the elegance of these mutations. “It’s so cool, it’s brilliant,” he said.

Having found these deletion mutations in viruses from one person, Dr. Duprex and his colleagues wondered how common they were.

Searching public databases of coronavirus genomes, they discovered that deletions were surprisingly widespread. “It’s happening independently in different parts of the world,” Dr. Duprex said.

All the deletions, it turns out, only arise in one region, the spike protein. Dr. Duprex and his colleagues found that deletions in the spike gene didn’t prevent the coronavirus from infecting cells.

Dr. Duprex and his colleagues posted their study online Nov. 19. It has not yet been published in a peer-reviewed journal. The researchers are now infecting animals with deletion-mutant viruses to better understand the risk they may pose to vaccines.

“Well, this paper does nothing to reduce the anxiety!” Dr. Read said in an email. “This is early data strongly suggesting the virus has the potential to escape human immunity.”

But Drs. Read and Kennedy argue that viral evolution won’t necessarily doom vaccines. Vaccine makers just need to stay aware of it, and devise new vaccines if necessary.

And there are numerous varieties of vaccines in development. The first two approaching approval in the United States both use a significant chunk of viral RNA to train the immune system. Other vaccines that are in development use the whole virus. And different vaccines deliver the virus or part of it in different ways, all of which could prompt a different immune response.
The New York Times

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