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Ebola Genomes Offer Look at Origin, Transmission Patterns of Virus in Ongoing Outbreak

NEW YORK (GenomeWeb) – An international team led by investigators in the US, Sierra Leone, and the UK has garnered genetic evidence suggesting that the current Ebola virus disease outbreak in West Africa involves a form of the virus not linked to recent outbreaks in the region.

Instead, the strain appears to have diverged from other Ebola virus lineages originating in Middle Africa around a decade ago.

As they reported online today in Science, the researchers sequenced the genomes of 99 Ebola virus isolates from 78 patients treated in Sierra Leone between late May and mid-June of this year.

Through comparisons with Ebola virus isolates identified in past outbreaks — as well as an analysis of genetic variants that cropped up within and between patients from the current outbreak — the team concluded that the current outbreak in West Africa was probably caused by two genetically distinct viruses from Guinea that were carried to Sierra Leone by a dozen people who had traveled to Guinea to attend a funeral.

"[T]he funeral attendees were most likely infected by two lineages then circulating in Guinea, possibly at the funeral" the researchers wrote. "All subsequent diversity in Sierra Leone accumulated on the background of those two lineages, consistent with epidemiological information from tracing contacts."

For their current analysis, the team started by using several library prep methods and sequencing technology combinations to assess 15 inactivated Ebola virus samples from a dozen patients.

After narrowing in on the most effective library construction and sequencing approaches, the researchers expanded their analysis to include more than 100 additional samples from patients with known or suspected Ebola virus infections.

In dozens of cases that tested negative for the virus, meanwhile, the group identified a range of other pathogens, including malaria parasites, HIV, and the hemorrhagic fever-causing Lassa virus.

All told, researchers obtained full genome sequences for 99 Ebola virus isolates from 78 individuals, sequenced to an average depth of around 2,000-fold coverage apiece on Illumina instruments.

When they compared the genomes of the Sierra Leone Ebola isolates with three previously sequenced Ebola virus isolates from Guinea, the investigators identified 341 fixed sequence substitutions in isolates from the current outbreak, along with dozens more single nucleotide sites that varied within the collection of Sierra Leone isolates.

At least some of these genetic changes are expected to alter the proteins produced by the virus, prompting interest in exploring the variant set for clues to preventing, diagnosing, and treating Ebola virus disease.

"[W]e don't know whether these differences are related to the severity of the current outbreak," co-first author Stephen Gire, a systems biology researcher working in co-senior author Pardis Sabeti's Harvard University and Broad Institute lab, said in a statement.

"[B]y sharing these data with the research community," Gire added, "we hope to speed up our understanding of this epidemic and support global efforts to contain it."

The team's broader phylogenetic comparison with 20 Ebola virus genomes obtained during past outbreaks pointed to divergence between the three outbreak lineages that stretches back roughly a decade. That, in turn, hints that each outbreak stemmed from a distinct human encounter with a natural reservoir of Ebola viruses present in Middle Africa.

In the case of the 2014 outbreak, for example, the researchers believe transmission to humans occurred just once, followed by infections caused as the virus moved from one person to another, first in Guinea and then in Sierra Leone.

The full genome sequences for the Ebola virus isolates described in the study were released to other researchers and infectious disease experts in June through the National Center for Biotechnology Information (NCBI) database.

"By making the data immediately available to the community, we hope to accelerate response efforts," co-senior author Pardis Sabeti, a researcher affiliated with Harvard University and the Broad Institute, said in a statement.

The Ebola virus has been implicated in more than 1,500 deaths so far in the ongoing outbreak in West Africa, according to the US Centers for Disease Control and Prevention. Among those who succumbed to the disease were four researchers involved in the current study, including co-senior author Humarr Khan, who was based at Sierra Leone's Kenema Government Hospital.

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