Viral Discovery Could Aid Vaccines, Treatments
A virus’s genetic loss can become its evolutionary gain.
This surprising discovery by Nebraska virologists provides some of the clearest experimental evidence that losing a gene can improve evolutionary fitness – in this case, by helping a virus regain the ability to replicate.
The team made the discovery after deleting the so-called B1 gene from the vaccinia virus. Because B1 helps silence a host’s antiviral alarms and allows vaccinia to copy itself, deleting the gene threatens vaccinia’s survival, said team leader Matt Wiebe, associate professor of veterinary medicine and biomedical sciences.
But the researchers continued culturing the B1-free strain before sequencing its genetic code to gauge how it evolved. The strain responded by deleting a single base pair – a fundamental component of DNA – while leaving nearly 200,000 others untouched. The seemingly miniscule loss corresponded with a 10-fold increase in the strain’s otherwise stunted replication.
From left, UNL virologist Matthew Wiebe, assistant professor in UNL’s School of Veterinary Medicine and Biomedical Science, and his research team, lab tech Prasanth Thunuguntla, graduate student Annabel Olson and postdoctoral researcher Augusta Jamin. April 9, 2015. Photo by Craig Chandler / University Communications“We were expecting that the virus may adapt another gene to compensate,” said Wiebe, a member of the Nebraska Center for Virology. “What we found instead is that the virus adapted by inactivating another gene. It was as if, upon cutting one wire, the best way to fix the problem was to cut another wire.”
That inactivation occurred in a gene, B12, whose purpose is largely unknown. Previously, when researchers elsewhere deactivated just the B12 gene, leaving all others intact, they found no effect on the vaccinia virus. Wiebe said the findings indicate that when B1
is absent – but only then – B12 actually inhibits viral replication by alerting the host’s immune system.
Leveraging that knowledge to hijack viral machinery could further the development of vaccines and treatments.
“It’s very interesting to understand what viruses might teach us,” said Wiebe, whose research was funded by the National Institutes of Health and the Fred & Pamela Buffett Cancer Center. “If this virus has a mechanism of activating our immune system, can we eventually use that to inhibit the growth of other viruses? We’re trying to ask those questions already.”
Additional content
Nebraska news release: Growing from loss: Virus deletes gene to regain replication
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