Genomic sequencing reveals origins, mutations of Ebola outbreak

An international team of researchers said Thursday they have rapidly sequenced and analyzed 99 genomes of the deadly Ebola virus, an important development that may assist global efforts to understand and contain the ongoing Ebola epidemic in West Africa.

The new study, published by the U.S. journal Science, also underscored the toll the current outbreak has taken on health workers on the front lines, as five of the nearly 60 co-authors from the U.S., UK, Sierra Leone and Nigeria contracted Ebola virus in the course of their work and died.

Previous outbreaks had been localized mostly to sparsely populated regions of Middle Africa, with the largest outbreak in 1976 reporting 318 cases.

The 2014 outbreak has manifested in the more densely-populated West Africa, and since it was first reported in Guinea in March 2014, more than 3,000 cases have been reported with 1,552 deaths. The World Health Organization (WHO) warned Thursday that the Ebola outbreak in West Africa eventually could exceed 20,000 cases.

In the new study, researchers sequenced 99 Ebola virus genomes collected from 78 patients diagnosed with Ebola in Sierra Leone during the first 24 days of the outbreak.

A portion of the patients contributed samples more than once, allowing researchers a clearer view into how the virus can change in a single individual over the course of infection.

"We've uncovered more than 300 genetic clues about what sets this outbreak apart from previous outbreaks," Stephen Gire, a research scientist in the Sabeti lab at the Broad Institute and Harvard University, said in a statement.

"Although we don't know whether these differences are related to the severity of the current outbreak, by sharing these data with the research community, we hope to speed up our understanding of this epidemic and support global efforts to contain it."

The researchers traced the transmission path and evolutionary relationships of the samples, revealing that the lineage responsible for the current outbreak diverged from the Middle African version of the virus within the last ten years. Earlier work had theorized that the virus had been circulating for decades in animals in West Africa but had not previously been detected.

Sequence variations also indicated that the current outbreak started from a single introduction into humans from an animal, thought to be fruit bats, subsequently spreading from person to person.

The study also found the virus spread from Guinea to Sierra Leone by 12 people, all females who had attended the funeral of a traditional healer who had treated Ebola patients in Guinea.

Of the 12 people was a young pregnant woman who was hospitalized with a fever and miscarried after the funeral. Tests showed the young woman, who eventually recovered, was the first confirmed case of Ebola in Sierra Leone.

Surprisingly, samples from the 12 people fell into two distant clusters, meaning the outbreak in Sierra Leone was sparked by at least two distinct viruses.

It is unclear whether the traditional healer in Guinea was infected with both variants, or whether perhaps another funeral attendee was independently infected.

"All subsequent diversity in Sierra Leone accumulated on the background of those two lineages, consistent with epidemiological information from tracing contacts," the researchers wrote in their paper.

In addition, the variations they identified were frequently in regions of the genome encoding proteins, including those that may affect the accuracy of the polymerase chain reaction (PCR)-based diagnostic tests. It emphasized the importance of genomic surveillance and the need for vigilance, the researcher said.

The research team released the full-length sequences online at the U.S. National Center for Biotechnology Information's DNA sequence database in June immediately after they were generated, making these data freely available to the global scientific community.

"By making the data immediately available to the community, we hope to accelerate response efforts," added co-author Pardis Sabeti, a senior associate member at the Broad Institute and an associate professor at Harvard University.