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Institut Pasteur Team Finds Three Distinct Ebola Virus Lineages in Guinea

NEW YORK (GenomeWeb) – A phylogenetic analysis of Ebola virus genomes from samples collected in Guinea last year found three distinct lineages that co-circulated in highly populated parts of the country.

The new study, led by researchers at the Institut Pasteur in Paris and in Dakar, Senegal, was published today in Nature. It follows two related reports of Ebola virus genome analyses in Guinea and Sierra Leone that were published in Nature and Cell last week by a European consortium and a US-led team, respectively.

For the latest project, the scientists sequenced 85 Ebola virus samples, collected from patients in Guinea who were infected between July and November of 2014. Most samples came from a mobile laboratory at Donka Hospital in the Guinean capital Conakry that was deployed by the Institut Pasteur of Dakar last March. Samples were processed in Dakar and sequenced on an Illumina HiSeq 2500 instrument in Paris.

Phylogenetic analysis of the Ebola genome data — together with 110 Ebola genome sequences from Guinea, Mali, and Sierra Leone that were already publicly available — revealed three distinct viral lineages in the Guinean samples. All three lineages co-circulated in Conakry last fall, highlighting "the challenge of controlling [Ebola virus] disease in and near large urban centers," the authors wrote.

The results appear to deviate somewhat from the European study published last week, which analyzed 179 patient samples and found two main viral lineages in Guinea. The difference can likely be explained by the fact that most of the samples in today's study came from the urbanized area of Conakry and surrounding districts, whereas most samples in the European study came from the forested areas of Guinea. "We must always remember that our molecular epidemiology is as good as the samples that we have had access to and sequenced," said Miles Carroll, a senior author of last week's study.

The Institut Pasteur researchers found the first lineage, which they called GUI-1, only in Guinea, both in urban and in forested areas. This lineage was most closely related to the earliest virus samples from the start of the outbreak. While the European consortium reported that this lineage — called lineage A in their study — no longer occurred in samples it analyzed after July 2014, the new study suggests the lineage remained in Conakry and neighboring districts, and might still persist to date.

Another lineage, called GUI-2, is closely related to a virus cluster circulating in Sierra Leone, SLE-2, and could have been either reintroduced from Sierra Leone to Guinea or could have developed independently within Guinea after it was introduced to Sierra Leone. The GUI-2 lineage also led to two separate Ebola introductions in Mali in late 2014.

A third virus cluster, SLE-GUI-3, was found in Conakry and surrounding towns, as well as in Sierra Leone. According to the researchers, the phylogenetic structure "suggests that there have been multiple migrations of [Ebola virus] into Guinea from Sierra Leone," although the virus could have traveled in the other direction, as well.

The presence of SLE-GUI-3 in both countries reflects "the continued mobility of individuals between these localities during the peak of the epidemic and in the face of outbreak control measures," they wrote, and the fact that all three lineages recurred in Conakry "is another indication of the challenges of controlling [Ebola virus] disease in large urban centers with highly mobile populations."

Etienne Simon-Loriere, an evolutionary biologist at the Institut Pasteur in Paris and the lead author of the study, told GenomeWeb that the main objective was to provide sequence data to researchers and healthcare workers quickly, both to ensure that currently used diagnostic tools are still adequate in the face of an evolving virus, and to support drug and vaccine research. The team made all sequences publicly available prior to publication, he said.

Fortunately, the genetic variation he and his colleagues detected "does not appear to create problems for the current diagnostic tools," in particular RT-qPCR, he said.

Also, none of the three lineages appear to have increased or decreased mortality. But each has a distinct combination of mutations, for example, in the virus' glycoprotein — a target of antibody drugs and of most vaccines — that "strongly warrant further functional investigation," he said.

The analysis also confirmed a finding of the other two studies, namely that the evolutionary rate of the virus is not as high as initially thought. "This is also quite reassuring," he said.