lunes, 27 de octubre de 2014

Investigating the Genomic Origins of the 2014 Ebola Outbreak

Investigating the Genomic Origins of the 2014 Ebola Outbreak National Human Genome Research Institute National Institutes of Health

Investigating the Genomic Origins of the 2014 Ebola Outbreak

Colorized scanning electron micrograph of filamentous Ebola virus particles (blue) budding from a chronically infected VERO E6 cell (yellow-green). Credit: National Institute of Allergy and Infectious Diseases, NIH
Ebola virus particles
Since March of this year, the Ebola virus in West Africa has infected and killed thousands of people in the region and gripped the world's attention. Despite treatment and containment efforts, the epidemic persists with a fatality rate of a staggering 52 percent, according to the World Health Organization.
The Ebola virus is a "zoonotic" disease, meaning it spreads between animals and humans, in this case from fruit bats to humans. Once in humans, it easily spreads from person to person through contact with blood and other body fluids. Complicating containment efforts, the virus has a long incubation period: a person can be infected for up to 21 days before symptoms appear. Because of this long period of infectivity and poor sanitation in the area, the epidemic has presented a massive challenge to healthcare workers.
But as the adage goes, knowledge is power, and a better understanding of the virus is an excellent start toward fighting the Ebola epidemic. This is why Stephen Gire, M.P.H., a research scientist at Harvard University in Boston, Massachusetts, and his colleagues used genomic sequencing techniques to study the current outbreak's origin, transmission and relation to other outbreaks.
For their study, published in the August 28 online issue of Science, Gire's group sequenced viral DNA of samples collected from 78 confirmed Ebola patients in Sierra Leone between late May and mid-June. For 13 of these patients, they collected samples at multiple time points, resulting in a total of 99 viral genome sequences. They compared these Ebola genomes to each other, as well as to three published genomes from Guinea, and 20 sequences generated from previous Ebola outbreaks.
The genomic analysis revealed that the current version of the virus in West Africa most likely spread from Middle Africa within the past 10 years. They also found that the viruses causing this outbreak and the two previous ones diverged from a common ancestor around 2004. This means that these outbreaks arose from different "jumps" from the animal reservoir to the human population. The similarity between samples from the current outbreak confirm that it originated from a single jump, and since that time the disease has spread exclusively from human to human. This is different from previous outbreaks, which had spread via multiple zoonotic events.
The authors' genomic detective work traces the outbreak in Sierra Leone to two genetically distinct viruses that spread from Guinea at around the same time, likely when 12 Sierra Leonean patients attended a funeral for a Guinean person who died of the virus.
Viral DNA, which replicates in the cells of the infected person, lacks the "proofreading" mechanism present in humans and other organisms that detects and corrects mistakes made during DNA replication. This lack of a proofreading mechanism results in a high rate of DNA mutation, allowing the virus to evolve quickly, adapt to new environments and elude potential treatments. By comparing Ebola genomes isolated during this outbreak, the group discovered that the virus exhibits a high rate of change to the DNA sequence, which alters the structure or function of the viral proteins (nonsynonymous genetic mutations). The authors emphasized the need for rapid and rigorous containment of the virus, as these mutations could make it much more difficult to treat, identify and contain.
To advance global efforts in fighting the outbreak, Gire and his colleagues have made the genome sequences available for use by other researchers. This will allow for more thorough epidemiological studies, and hopefully make the containment effort more effective.
Unfortunately, the paper ends on a tragic note. While working in affected areas, five of the paper's co-authors contracted the virus and died. Such losses underscore the importance of studying the outbreak, and the bravery and sacrifice of those willing to do so.
Read the Study
Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara FK, Tucker V, Konuwa E, Saffa S, Sellu J, Jalloh AA, Kovoma A, Koninga J, Mustapha I, Kargbo K, Foday M, Yillah M, Kanneh F, Robert W, Massally JL, Chapman SB, Bochicchio J, Murphy C, Nusbaum C, Young S, Birren BW, Grant DS, Scheiffelin JS, Lander ES, Happi C, Gevao SM, Gnirke A, Rambaut A, Garry RF, Khan SH, Sabeti PC. Science, 345(6202):1369-72. 2014. [Full Text]

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