Study shows high frequency of spontaneous mutation in Ebola virus

Ebola is a deadly form of viral hemorrhagic fever occurring in humans and other primates and is caused by Ebola viruses. It is understood that this virus transmitted to humans from wild animals and eventually spread in the human population through human-to-human transmission. The disease has an average fatality rate of 50%. Once the virus is contracted the symptoms appear between two days to three weeks. The typical symptoms include fever, sore throat, muscular pain, and headaches followed by vomiting, diarrhea along with decreased function of the liver and kidneys.

Ebola

The latest and perhaps the biggest outbreak of this epidemic happened in March 2014 in West Africa. Almost after two years since the epidemic began, the World Health Organization has declared the African country of Guinea to be free of Ebola virus infections. However, the race to find a cure and therapies to combat the disease are on, as officials are of the opinion that inattention could lead to another deadly epidemic.

Scientists at Texas Biomedical Research Institute have been working on therapies, diagnostics and vaccines for years before the 2014 epidemic. Finally, they seem to have discovered a promising mechanism for attacking the virus reveals a recent study by Dr. Anthony Griffiths. This study is scheduled to be published in the Journal of Virology – Issue 5 March 2016 print edition. However, it can be accessed online already.

Dr. Griffiths, in his paper titled Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency, 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. But, it was unknown whether filoviruses exhibit high mutation frequencies. He added that when the work on this study was at its initial stage, there was not an appreciation that Ebola virus had any capacity to evolve and if those changes would be well tolerated.

Kendra Alfson, a graduate student in Griffiths' team along with his mentor used ultra-deep sequencing to find that the spontaneous mutation frequency for Ebola virus was high and similar to other RNA viruses. But, it was also found that Ebola virus had very limited ability to tolerate spontaneous changes in the genome. That is why it was reasoned that chemically increasing the mutation frequency may decrease the number of viable virions released from a cell. Typically, it was understood that Ebola virus has the potential to evolve rapidly however, the genetic changes result in viruses that are weakened or not viable. But, since the latest outbreak had an unprecedented numbers of individuals infected, it is now evident that Ebola virus does evolve in humans. Hence, to have better diagnostics and potential therapies for the condition, a better understanding of the capacity of the virus to evolve is essential.

Griffiths explains that any change in a genome can be neutral, negative, or positive to a virus. It may seem that viruses have evolved to have an optimal mutation rate. But, increasing the mutation rate could produce a negative effect on the virus and serve as a valuable therapeutic tool. In order to determine whether Ebola virus was sensitive to increasing mutation rate, Griffiths’ team tested a drug called ribavirin. The preliminary experiments with mice suggest ribavirin could be a potential therapy as it did cause the desired effect of increasing the mutation frequency enough to make the virus non-viable. When further tests were carried out in monkeys, it was seen that ribavirin reduced production of infectious Ebola virus; however results were not strong enough to recommend ribavirin as a treatment protocol.

Griffith opined that since modifying mutation rate as a therapeutic tool for Ebola virus infections seems promising, the future course of action is to test other drugs in the hope of improving the efficacy observed using ribavirin.

References:

https://www.txbiomed.org/news-press/detail/news/2016/01/05/ebola-mutation-frequency

https://medicalxpress.com/news/2016-01-high-frequency-spontaneous-mutation-ebola.html