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Abstractions

First author

Many viral pathogens and their hosts are locked in a never-ending molecular arms race. Some viruses interfere with host immuity by encoding mimics of key host proteins. Poxvirus, for example, encodes a protein that competes with the substrate acted on by protein kinase R (PKR) — a mammalian protein that blocks viral replication. On page 485, Nels Elde, a postdoc at the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues detail how primate PKR hits back, evolving to counter poxvirus mimicry. Elde tells Nature that molecular mimicry is a widespread evolutionary strategy.

When did you realize that mimicry is important for poxvirus evolution?

Our lab focuses on the evolutionary strategies that organisms use to defeat one another. Mimicry was largely uncharted territory, and was intriguing because it changes how we think about conflict. Turning the host against itself adds another layer of biological complexity. When we found that PKR is one of the fastest evolving primate genes, we knew it was responding to assaults and could be a target of mimicry. The poxvirus genome we studied comprises roughly 200 genes, and at least 10 of these are mimics.

How does mimicry evolve?

In a number of cases, mimicry starts when a pathogen 'steals' its host's genetic material through horizontal gene transfer, a process often used by viruses to take up foreign genetic material and incorporate it into their genomes. Over time, if the stolen gene proves to be a viable mimic, it can evolve to disrupt the host's normal protein interactions.

How can a host outfox a pathogen mimic?

This was our main question because most viruses evolve more rapidly than their hosts. One of the big surprises for us was the finding that primate hosts can make multiple, simultaneous changes to its proteins. So although the host evolves more slowly, it evolves in ways that level the playing field.

Do all hosts win out?

We looked at 20 different close and distant primate relatives. We found that humans, chimpanzees and orangutans are resistant to the poxvirus mimic, whereas gibbons, as well as most Old and New World monkeys, are quite susceptible. But our close relatives are resistant for different reasons, which indicates that species can adapt differently even when faced with similar arms races.

What's next for you?

This work focused on the host evolution side of things, but I also want to investigate how pathogens evolve.

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Abstractions. Nature 457, 356 (2009). https://doi.org/10.1038/7228356b

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