Immunity system complexity: viruses fight bat immunity (Introduction)

by David Turell , Thursday, November 24, 2022, 17:17 (862 days ago) @ David Turell

Bats have duplicted a gene in the fight:

https://www.the-scientist.com/news-opinion/duplicated-gene-helps-bats-survive-arms-race...

"Bats are highly unusual creatures...as probes into the origin of the COVID-19 pandemic emphasize, they can harbor myriad viruses that are dangerous or fatal to other mammals without getting sick themselves.

"According to research published today (November 23) in Science Advances, bats’ ability to survive as so-called viral reservoirs may stem in part from unique mutations, including the duplication of the gene encoding an antiviral protein called protein kinase R (PKR). That second copy stems from an ongoing evolutionary “arms race,” according to the study, resulting in bats’ adaptation to and seeming immunity from a wide range of viruses over the course of their evolutionary history.

“'The biggest surprise to me is the extra copies of PKR in the genomes of some bat species,” study coauthor Nels Elde, a geneticist at the University of Utah and the Howard Hughes Medical Institute, tells The Scientist over email. “Even cooler is the new evidence that these copies diverge and can become less vulnerable to virus-encoded inhibitors of PKR. It looks like two PKRs can be better than one.”

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"With that genomic data in hand, the researchers found that the gene EIF2AK2, which encodes PKR, rapidly evolved and underwent at least one duplication event early enough in bats’ evolutionary history that the extra copy was present in every species they sampled. Some species had more than two copies of EIF2AK2; or closely related sequences, they found, many of which encoded paralogs of PKR and share its primary function as a frontline defense against viral invaders that blocks the translation of viral DNA and RNA. Comparing these sequences to those of humans, mice (Mus musculus), cows (Bos taurus), and dogs (Canis lupus familiaris), the team found that PKR duplication is indeed unique to bats.

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"To test the function of bats’ multiplicity of PKRs, the researchers gene-edited yeast to produce various bat PKRs or its orthologs, then exposed the cells to known kinase antagonists taken from bat-infecting viruses, including poxviruses, herpesviruses, and orthomyxoviruses. They found that PKR deploys an array of mechanisms to combat various viruses, suggesting that over time, viruses evolved to counteract bats’ existing defense mechanisms, and bats evolved new-and-improved PKRs in response. Alexa Sadier, a University of California, Los Angeles, evolutionary developmental biologist who didn’t work on the study, explains that this finding is a clear-cut example of the Red Queen hypothesis, named after a character in Alice in Wonderland, which posits that a sort of evolutionary arms race occurs between predators and prey, or in this case viruses and their host, in which the selective pressure imposed by an adaptation in one imposes new pressures—and adaptations—in the other. “The host will adapt and the virus will adapt,” she says. “This is really aligned with what we know.”

"'Functionally, having multiple copies of the gene allowed the extras to diverge and produce proteins that are more resistant to viral inhibitors, Elde says. “Almost like a game of evolutionary hot potato where if the virus blocks one copy of PKR, the other one might be more active during infections. If the virus blocks the other, the original copy of PKR might be more effective'.”

Comment: presented to illustrate the power of immune systems in all organisms