Study shows high frequency of spontaneous mutation in Ebola virus

January 05, 2016

SAN ANTONIO (January 5, 2016) - In late December, nearly two years after the epidemic began, the World Health Organization has declared the African country of Guinea to be free of Ebola virus infections. But, the race to find a cure and therapies to combat the disease are forging ahead as officials warn that inattention could lead to another epidemic.

Texas Biomedical Research Institute scientists have been working on therapies, diagnostics and vaccines for years before the 2014 epidemic, and a recent study by Dr. Anthony Griffiths to be published in the Journal of Virology shows a promising mechanism for attacking the virus. The paper will be in Issue 5 March 2016 print edition but is already available online - doi:10.1128/JVI.02701-15.

In the paper, titled Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency, Dr. Griffiths 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 exhibit high mutation frequencies.

"When we started this work, there was not an appreciation that Ebola virus had any capacity to evolve and if those changes would be well tolerated," Griffiths explained.

Griffiths and his team, that included graduate student Kendra Alfson, used ultra deep sequencing to reveal that the spontaneous mutation frequency for Ebola virus was high and similar to other RNA viruses. However, "We found that Ebola virus had very 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 virus 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, we have learned that Ebola virus 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," Griffiths explained. He added 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, Griffiths' group tested a drug called 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 non-viable. 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," Griffiths said. "We plan to test other drugs in the hope of improving the efficacy observed using ribavirin."
The Journal of Virology has published an ahead of print version online at Biomed is one of the world's leading independent biomedical research institutions dedicated to advancing health worldwide through innovative biomedical research. Texas Biomed partners with hundreds of researchers and institutions around the world to develop vaccines and therapeutics against viral pathogens causing AIDS, hepatitis, herpes, hemorrhagic fevers and parasitic diseases responsible for malaria, schistosomiasis and Chagas disease. The Institute also has programs in the genetics of cardiovascular disease, diabetes, obesity, psychiatric disorders and other diseases. For more information on Texas Biomed, go to

Texas Biomedical Research Institute

Related Ebola Virus Articles from Brightsurf:

Targeting the shell of the Ebola virus
As the world grapples with COVID-19, the Ebola virus is again raging.

New universal Ebola vaccine may fight all four virus species that infect humans
Infectious disease scientists report early development of a potential universal vaccine for Ebola viruses that preclinical tests show might neutralize all four species of these deadly viruses infecting people in recent outbreaks, mainly in Africa.

Researchers show how Ebola virus hijacks host lipids
Robert Stahelin studies some of the world's deadliest viruses. Filoviruses, including Ebola virus and Marburg virus, cause viral hemorrhagic fever with high fatality rates.

Recognise and control new variants of the deadly Ebola virus more quickly
Joint press release by the DZIF and Charité. The situation is extraordinary: there have only ever been four declarations of public health emergencies of international concern in the past and now there are two at the same time.

Investigational drugs reduce risk of death from Ebola virus disease
The investigational therapeutics mAb114 and REGN-EB3 offer patients a greater chance of surviving Ebola virus disease (EVD) compared to the investigational treatment ZMapp, according to published results from a clinical trial conducted in the Democratic Republic of the Congo (DRC).

Researchers learn how Ebola virus disables the body's immune defenses
A new study by researchers from The University of Texas Medical Branch at Galveston uncovered new information on why the Ebola virus can exert such catastrophic effects on the infected person.

Mutant live attenuated Ebola virus immunizes non-human primates
Inoculation with an Ebola virus that has mutations in a protein called VP35 does not cause disease and elicits protection in monkeys, researchers show Sept.

Groundbreaking study could lead to fast, simple test for Ebola virus
In a breakthrough that could lead to a simple and inexpensive test for Ebola virus disease, researchers have generated two antibodies to the deadly virus.

RIT professor develops microfluidic device to better detect Ebola virus
A faculty-researcher at Rochester Institute of technology has developed a prototype micro device with bio-sensors that can detect the deadly Ebola virus.

NEJM applying universal standards of care to Ebola virus disease
LSTM's Senior Clinical Lecturer, Dr. Shevin Jacob, is corresponding author on a perspective piece published in the New England Journal of Medicine calling for universal standards of care to be applied in relation to ebola virus disease.

Read More: Ebola Virus News and Ebola Virus Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to