The Latest COVID Variants Have a Surprising Feature in Common

[Nevilledog]

https://www.theatlantic.com/science/archive/2023/05/coronavirus-evolution-orf8-protein-gene-loss/674017/

No paywall
https://archive.is/vB294

The coronavirus genome is 30,000 letters long, encoding more than two dozen different proteins that enable the virus to hijack our cells. Of these, spike gets all the glory and infamy; it is the protein targeted by vaccines, and it is the protein that keeps shape-shifting in new variants. But lately, something strange has been happening with another protein called ORF8, once thought to be a crucial player. The virus keeps losing ORF8—over and over again.

It happened first in Alpha. Then again more recently with the Omicron subvariant BA.5, and now again with the ascendant XBB.1.16, also known as the Arcturus variant. In a few weeks’ time, more than 90 percent of SARS-CoV-2 viruses circulating will likely be missing an intact ORF8. All of this is especially strange, if you are to believe the scientific literature, which has posited several different key roles for ORF8: evading T cells, disrupting human gene regulation, mimicking a human immune protein, and more. Scientists have published whole papers devoted to the importance of ORF8, only to have it disappear repeatedly.

So is ORF8 simply unimportant enough—contra prior claims—that the coronavirus can keep infecting humans just fine without it? Or is the virus actually gaining an advantage from ditching this protein? Losing ORF8 is unlikely to be a big, Omicron-level evolutionary leap, but no one can say for sure why it’s happening. The evolution of SARS-CoV-2 has repeatedly surprised us over the past three and a half years. Even now, this virus that is perhaps the most intensely scrutinized virus of all time has its mysteries.

These questions have captivated a community of online genetic sleuths. Two of the authors of a recent informal report on the loss of ORF8, Ryan Hisner and Federico Gueli, are not professional scientists. “These guys have become, genuinely, some of the world’s experts of the up-to-the-moment variant stuff,” says Thomas Peacock, a virologist at the Pirbright Institute and the report’s third author. When SARS-CoV-2 sequences get shared publicly, a group of variant hunters—both amateurs and professionals—search through the proverbial haystack, looking for variants and mutations rising in prevalence. Variant-hunting used to be the domain of professional scientists with supercomputers. But the novelty of the coronavirus—no one was a SARS-CoV-2 expert before 2020—and the popularization of new tools that make the work less computationally intensive have allowed dedicated amateurs to become the world’s experts. Hisner, a schoolteacher in Indiana, is now starting a master’s program on account of his mutation work.

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