Using Evolution to Trap HIV, Stop Drug Resistance
Scanning electron micrograph of HIV-1 budding (in green) from cultured lymphocyte. This image has been colored to highlight important features. Multiple round bumps on cell surface represent sites of assembly and budding of virions.
In an effort to understand how HIV evolves resistance to drugs, a Michigan State University researcher has found that it may be possible to steer the evolution of HIV proteins, and eventually make HIV stop evolving.
Chris Adami, professor of microbiology and molecular genetics at MSU, found that in patients who have never taken medications to treat HIV, the virus’ proteins don’t evolve. However, patients who were on anti-viral drugs saw their viral proteins evolve quickly, and in a very particular way.
Using information about the protein sequences of patients who are taking anti-viral medications, Adami and Aditi Gupta, co-author and postdoctoral researcher, Rutgers Medical School, found that continued exposure to drugs limits the changes to the viral proteins, making continued evolution more difficult.
“You think of evolution as always finding a way. But we found instead that when an organism must adapt quickly, the fast way to adapt may doom your long-term adaptive potential,” Adami said.
A protein’s structure can be thought of as a set of beads connected with ties. To change, either the beads or the ties must change. The team found that when a protein needs to adapt quickly, it does so by introducing new ties and rearranging the existing ones, as opposed to just changing the beads. However, the new ties eventually “tie down” the protein, making further changes all the more difficult. If tied down sufficiently, the protein’s evolution must drastically slow down.
By studying the evolution of a particular viral protein for ten years, the team was able to observe precisely how the protein changes. “We show that HIV has successfully adapted to stronger and stronger medications over the years,” Gupta said. “It takes a lot of money and time to develop new and better drugs, yet the virus can evolve drug-resistance in a matter of months, if not weeks.”
HIV evolution might be the answer to addressing the problem of drug-resistance and to increase the longevity of available drugs, Adami said.
“We may one day be able to introduce new drugs strategically to purposefully tie down the protein. Thus, research on slowing down evolution may become as important as finding out how to accelerate evolution,” he said.
The paper, “Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein,” appears in PLoS Genetics.
– Kim Ward, Chris Adami via MSU Today