In response to
an ongoing, unprecedented outbreak of Ebola virus disease (EVD) in West
Africa, a team of researchers from the Broad Institute and Harvard
University, in collaboration with the Sierra Leone Ministry of Health
and Sanitation and researchers across institutions and continents, has
rapidly sequenced and analyzed more than 99 Ebola virus genomes. Their
findings could have important implications for rapid field diagnostic
tests. The team reports its results online in the journal Science.
Created by CDC microbiologist Frederick A. Murphy, this colorized
transmission electron micrograph (TEM) revealed some of the
ultrastructural morphology displayed by an Ebola virus virion.
For the current 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). The team found more than 300 genetic changes that make the
2014 Ebola virus genomes distinct from the viral genomes tied to
previous Ebola outbreaks. They also found sequence variations indicating
that, from the samples sequenced, the EVD outbreak started from a
single introduction into humans, subsequently spreading from person to
person over many months.
The variations they identified were frequently in regions of the
genome encoding proteins. Some of the genetic variation detected in
these studies may affect the primers (starting points for DNA synthesis)
used in PCR-based diagnostic tests, emphasizing the importance of
genomic surveillance and the need for vigilance. To accelerate response
efforts, the research team released the full-length sequences on
National Center for Biotechnology Information's (NCBI's) DNA sequence
database in advance of publication, making these data available to the
global scientific community.
"By making the data immediately available to the community, we hope
to accelerate response efforts," said co-senior author Pardis Sabeti, a
senior associate member at the Broad Institute and an associate
professor at Harvard University. "Upon releasing our first batch of
Ebola sequences in June, some of the world's leading epidemic
specialists contacted us, and many of them are now also actively working
on the data. We were honored and encouraged. A spirit of international
and multidisciplinary collaboration is needed to quickly shed light on
the ongoing outbreak."
The 2014 Zaire ebolavirus (EBOV) outbreak is unprecedented
both in its size and in its emergence in multiple populated areas.
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, 2,240 cases have been reported with 1,229 deaths (as of
August 19).
Augustine Goba, Director of the Lassa Laboratory at the Kenema
Government Hospital and a co-first author of the paper, identified the
first Ebola virus disease case in Sierra Leone using PCR-based
diagnostics. "We established surveillance for Ebola well ahead of the
disease's spread into Sierra Leone and began retrospective screening for
the disease on samples as far back as January of this year," said Goba.
"This was possible because of our long-standing work to diagnose and
study another deadly disease, Lassa fever. We could thus identify cases
and trace the Ebola virus spread as soon as it entered our country."
The research team increased the amount of genomic data available on
the Ebola virus by four fold and used the technique of "deep sequencing"
on all available samples. Deep sequencing is sequencing done enough
times to generate high confidence in the results. In this study,
researchers sequenced at a depth of 2,000 times on average for each
Ebola genome to get an extremely close-up view of the virus genomes from
78 patients. This high-resolution view allowed the team to detect
multiple mutations that alter protein sequences -- potential targets for
future diagnostics, vaccines, and therapies.
The Ebola strains responsible for the current outbreak likely have a
common ancestor, dating back to the very first recorded outbreak in
1976. The researchers also 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 and spread from Guinea to Sierra Leone
by 12 people who had attended the same funeral.
The team's catalog of 395 mutations (over 340 that distinguish the
current outbreak from previous ones, and over 50 within the West African
outbreak) may serve as a starting point for other research groups.
"We've uncovered more than 300 genetic clues about what sets this
outbreak apart from previous outbreaks," said Stephen Gire, a research
scientist in the Sabeti lab at the Broad Institute and Harvard.
"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."
"There is an extraordinary battle still ahead, and we have lost many
friends and colleagues already like our good friend and colleague Dr.
Humarr Khan, a co-senior author here," said Sabeti. "By providing this
data to the research community immediately and demonstrating that
transparency and partnership is one way we hope to honor Humarr's
legacy. We are all in this fight together."
This work was supported by Common Fund and National Institute of
Allergy and Infectious Diseases in the National Institutes of Health,
Department of Health and Human Services, as well as by the National
Science Foundation, the European Union Seventh Framework Programme, the
World Bank, and the Natural Environment Research Council.
Other researchers who contributed to this work include Augustine
Goba, Kristian G. Andersen, Rachel S. G. Sealfon, Daniel J. Park,
Lansana Kanneh, Simbirie Jalloh, Mambu Momoh, Mohamed Fullah, Gytis
Dudas, Shirlee Wohl, Lina M. Moses, Nathan L. Yozwiak, Sarah Winnicki,
Christian B. Matranga, Christine M. Malboeuf, James Qu, Adrianne D.
Gladden, Stephen F. Schaffner, Xiao Yang, Pan-Pan Jiang, Mahan Nekoui,
Andres Colubri, Moinya Ruth Coomber, Mbalu Fonnie, Alex Moigboi, Michael
Gbakie, Fatima K. Kamara, Veronica Tucker, Edwin Konuwa, Sidiki Saffa,
Josephine Sellu, Abdul Azziz Jalloh, Alice Kovoma, James Koninga,
Ibrahim Mustapha, Kandeh Kargbo, Momoh Foday, Mohamed Yillah, Franklyn
Kanneh, Willie Robert, James L. B. Massally, Sinéad B. Chapman, James
Bochicchio, Cheryl Murphy, Chad Nusbaum, Sarah Young, Bruce W. Birren,
Donald S.Grant, John S. Scheiffelin, Eric S. Lander, Christian Happi,
Sahr M. Gevao, Andreas Gnirke, Andrew Rambaut, Robert F. Garry, and S.
Humarr Khan.
Journal Reference:
- Gire, SK, Goba, A et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science, 2014 DOI: 10.1126/science.1259657
Courtesy: ScienceDaily
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