Gene studies of Ebola in Sierra Leone show virus is mutating fast

By Julie Steenhuysen

CHICAGO, Aug 28 (Reuters) - Genetic studies of some of theearliest Ebola cases in Sierra Leone reveal more than 300genetic changes in the virus as it leapt from person to person,changes that could blunt the effectiveness of diagnostic testsand experimental treatments now in development, researchers saidon Thursday.

"We found the virus is doing what viruses do. It'smutating," said Pardis Sabeti of Harvard University and theBroad Institute, who led the massive study of samples from 78people in Sierra Leone, all of whose infections could be tracedto a faith healer whose claims of a cure attracted Ebolapatients from Guinea, where the virus first took hold.

The findings, published in Science, suggest the virus ismutating quickly and in ways that could affect currentdiagnostics and future vaccines and treatments, such asGlaxoSmithKline's Ebola vaccine, which was justfast-tracked to begin clinical trials, or the antibody drugZMapp, being developed by California biotech MappBiopharmaceutical.

The findings come as the World Health Organization said thatthe epidemic could infect more than 20,000 people and spread tomore countries. A WHO representative could notimmediately be reached for comment on the latest genetic study.

Study coauthor Robert Garry of Tulane University said thevirus is mutating at twice the rate in people as it was inanimal hosts, such as fruit bats.

Garry said the study has shown changes in the glycoprotein,the surface protein that binds the virus to human cells,allowing it to start replicating in its human host. "It's alsowhat your immune system will recognize," he said.

In an unusual step, the researchers posted the sequencesonline as soon as they became available, giving otherresearchers early access to the data.

Erica Ollmann Saphire of the Scripps Research Institute inLa Jolla, California, has already checked the data to see if itimpacts the three antibodies in ZMapp, a drug in short supplythat has been tried on several individuals, including the twoU.S. missionaries who contracted Ebola in Sierra Leone and whohave since recovered.

"It appears that they do not (affect ZMapp)," said Saphire,who directs a consortium to develop antibody treatments forEbola and related viruses. But she said the data "will becritical to seeing if any of the other antibodies in our poolcould be affected."

Saphire said the speed with which Sabeti and colleaguesmapped genetic changes in the virus gives researchersinformation that "will also be critical" to companies developingRNA-based therapeutics.

That could impact treatments under way from Vancouver-basedTekmira Pharmaceuticals Corp and privatelyheld Profectus BioSciences of Tarrytown, New York.

Part of what makes the data useful is the precise picture itpaints as the epidemic unfolded. Sabeti credits years of work byher lab, colleagues at Tulane and the Sierra Leone Ministry ofHealth and Sanitation in developing a response network for Lassafever, a virus similar to Ebola that is endemic in West Africa.

Several of the study authors gave their lives to the work,including Dr Sheik Humarr Khan, the beloved "hero" doctor fromthe Kenema Government Hospital, who died fromEbola.

The team had been doing surveillance for two months when thefirst case of Ebola arrived from Guinea on May 25. That caseinvolved a "sowei" or tribal healer, whose claim of a cure luredsick Ebola victims from nearby Guinea.

"When she contracted Ebola and died, there were a lot ofpeople who came to her funeral," Garry said. One of these was ayoung pregnant woman who became infected and traveled to KenemaGovernment Hospital, where she was diagnosed with Ebola.

With the Lassa surveillance team in place, they quicklybegan testing samples.

"We've been able to capture the initial spread from that oneperson and to follow all of these contacts and everything withsequencing," Garry said.

The team used a technique called deep sequencing in whichsequences are done repeatedly to generate highly specificresults, allowing them to see not only how the virus is mutatingfrom person to person, but how it is mutating in cells withinthe same person.

What is not clear from the study is whether the mutationsare fueling the epidemic by allowing the virus to grow better inpeople and become easier to spread. That will require furthertests in the lab, Garry said.

(Editing by Matthew Lewis)