The Plastic Genome

The poxvirus stockpiles genes when it needs to adapt.

Dec 1, 2012
Beth Marie Mole

EDITOR'S CHOICE IN VIROLOGY

THE VIRAL ACCORDION: In times of stress, vaccinia viruses (blue) expand their DNA (green) by making duplicate copies of beneficial genes.© SPL/SCIENCE SOURCE

The paper
N.C. Elde et al., “Poxviruses deploy genomic accordions to adapt rapidly against host antiviral defenses,” Cell, 150:831-41, 2012.

The finding
Double-stranded DNA viruses, such as poxviruses, were thought to mutate slowly despite keeping pace with rapidly shifting host defenses. Now, Harmit Malik at the Fred Hutchinson Cancer Research Center and colleagues have found that poxviruses expand their genome—making duplicate copies of genes—which allows more beneficial mutations to arise and hastens adaptive viral offensives.

The war zone
Nels Elde, at the time a postdoc in Malik’s lab, grew vaccinia virus in unfavorable conditions, namely in human cells that produced a viral inhibitor named protein kinase R (PKR). Although vaccinia virus carries a gene for one version of a PKR antagonist called K3L—a protein that usually undermines the inhibitory action of the kinase—this version was poorly adapted to the PKR in Elde’s cells. “We just asked the virus, ‘What do you do, how do you solve that puzzle?’” says Elde, now an assistant professor at the University of Utah.

The explosion
After several poor passages in the unfavorable cell line, the poxvirus’s replication picked up. The team sequenced the viral genome, finding it up to 7–10 percent larger, with a spike in number of gene copies that encode K3L—and a helpful point mutation in some copies. When they subsequently grew the adapted virus in a hamster cell line—in which viral K3L functions effectively—the genome shrank again.

The aftermath
This could be the end of a theoretical battle, says University of California, Davis, microbiologist John Roth, who was not involved in the study. Instead of the old theory that organisms might speed up mutation rates, this suggests “they exploit this natural system to get enough targets at the same old mutation rate,” he says.