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January 5, 2016

Ebola’s High Mutation Rate Could Be Its Achilles Heel

  • Researchers at the Texas Biomedical Research Institute completed a study that concluded that the high mutation rate of the Ebola virus may provide the basis for developing effective therapies.

    In an online paper (" Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency”), published in the Journal of Virology, Anthony Griffiths, Ph.D., associate scientist, explains how "typically, RNA viruses have high spontaneous mutation rates, which permit rapid evolution and the ability to adapt to new selection pressures. These selection pressures can include antiviral drugs, the immune system, or even new animal hosts." However, it was unknown whether filoviruses, including Ebola, exhibit high mutation frequencies and if those changes would be well tolerated.

    Dr. Griffiths and his team used ultra deep sequencing to reveal that the spontaneous mutation frequency for Ebola virus was high and similar to other RNA viruses. However, the investigators  also found that Ebola had limited ability to tolerate spontaneous changes in the genome. thus it was reasoned that chemically increasing the mutation frequency may decrease the number of viable virions released from a cell."

    Essentially, Ebola has the potential to evolve rapidly but the genetic changes result in viruses that are weakened or not viable. Due to the unprecedented numbers of individuals infected in the latest outbreak, researchers learned that Ebola does evolve in humans. Therefore, a better understanding of the capacity of the virus to evolve could lead to better diagnostics and potential therapies.

    "Any change in a genome can be neutral, negative, or positive to a virus," says Dr. Griffiths, adding that "interestingly, viruses appear to have evolved to have an optimal mutation rate. Increasing the mutation rate could produce a negative effect on the virus and serve as a valuable therapeutic tool."

    To determine whether Ebola virus was sensitive to increasing mutation rate, Dr. Griffiths' group tested the drug ribavirin. Preliminary experiments with mice suggested ribavirin could be a potential therapy and did cause the desired effect of increasing the mutation frequency enough to make the virus nonviable. Further testing in monkeys showed ribavirin reduced production of infectious Ebola virus but results were not strong enough to recommend ribavirin as a treatment protocol.

    "Now we have shown the potential of modifying mutation rate as a therapeutic tool for Ebola virus infections," continues Dr. Griffiths. "We plan to test other drugs in the hope of improving the efficacy observed using ribavirin."

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