Debunking myths on genetics and DNA

Sunday, October 26, 2014

Ebola could mutate as rapidly as the flu

© Science Magazine

The largest genomic data collected on the Ebola virus to date has been recently published in Science [1], giving unique insights on the origin and spread of the greatest Ebola outbreak so far.

The Ebola virus was first discovered in 1976, when it caused 318 cases: until now, it was the largest outbreak.
"The current outbreak started in February 2014 in Guinea, West Africa, and spread into Liberia in March, Sierra Leone in May, and Nigeria in late July. It is the largest known EVD outbreak and is expanding exponentially [1]."
In a recent Science paper [1], researchers sequenced 99 Ebola genomes from 78 patients from Sierra Leone. By analyzing the genetic make-up of the viral population, scientists can retrace the spread of the outbreak. It's a bit like looking at the DNA of a large group of people to find out who's related to whom. In the case of Ebola, we want to know if there was only one "parent", so to speak, or if there were several animal-to-human reinsertions.

According to the paper, the event that brought the virus to Sierra Leone at the end of May was the burial of a healer from Guinea who had treated Ebola patients. Local practices at funerals include touching and kissing the corpse, and given that Ebola can survive in a dead host for up to three days, you can see how a single funeral can infect dozens of people, especially when the dead is a popular healer as in this particular case. Thirteen cases were traced back to this funeral, two of which stemmed the outbreak in Sierra Leone.

The researchers analyzed the viral genomes using phylogenetic trees, a technique that enabled them to retrace the history of the virus.
"Phylogenetic comparison to all 20 genomes from earlier outbreaks suggests that the 2014 West African virus likely spread from central Africa within the past decade [1]."
They were able to see that the "ancestor" originated from a single transmission event back in February. This finding contradicts previous hypothesis that the unprecedented spread of the outbreak was due to multiple transmission events from animal to humans. Contrary to this hypothesis, after that first transmission, in which the virus jumped from animals to human back in February, Ebola has been spreading among people alone.
"Genetic similarity across the sequenced 2014 samples suggests a single transmission from the natural reservoir, followed by human-to-human transmission during the outbreak. Molecular dating places the common ancestor of all sequenced Guinea and Sierra Leone lineages around late February 2014, 3 months after the earliest suspected cases in Guinea; this coalescence would be unlikely had there been multiple transmissions from the natural reservoir [1]."
But the most interesting point (to me at least) that the paper addresses is the virus's mutation rate. Since viruses replicate quite rapidly, it's important to know how high is the chance that at every replication cycle, errors (i.e. mutations) are introduced. Rapidly mutating viruses have a greater chance to escape the immune system (see HIV, for example) and are also much harder to target with a vaccine. The Science paper claims that
"The observed substitution rate is roughly twice as high within the 2014 outbreak as between outbreaks [1]."
In fact, they estimate the mutation rate to be roughly the same as that of the seasonal flu, which, if confirmed, would greatly hamper the creation of a vaccine.

Unfortunately the odds are still against poor countries. I attended a talk this week where the speaker reported that while the mortality rate in the affected African countries is at 95%, in the Western world it drops down to 75-80%. This is due to prompt intervention, the use of serum from people who survived the infection (and hence developed good antibodies against the virus), and the use of IVs. Unfortunately, people living in the affected countries tend to be skeptical of westerners and, just like it happened with HIV, beliefs that Ebola is yet another virus introduced by Westerners to hurt the locals are rampant.

When I finished reading the Science paper, I was saddened to find this final paragraph:
"In memoriam: Tragically, five co-authors, who contributed greatly to public health and re- search efforts in Sierra Leone, contracted EVD and lost their battle with the disease before this manuscript could be published: Mohamed Fullah, Mbalu Fonnie, Alex Moigboi, Alice Kovoma, and S. Humarr Khan. We wish to honor their memory."

[1] 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 (2014). Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science (New York, N.Y.), 345 (6202), 1369-72 PMID: 25214632


  1. I posted this comment on facebook, too.Thank you for this, Elena. I admire your request for additional information. I don't know a lot about viruses or even about potential mutations. I'm unsure of the definition of "site" when used in this context. Is a "site" an instance of infection in a host? Because if that is the case, I too find 8 X 10-4 to be rather terrifying.

    1. Hi Teresa, site is a base position in the genome. So, for example, HIV has a mutation rate of 2.16e-05 per cycle per site. The HIV genome is roughly 9,000 sites long, so that means that for every replication cycle there's roughly a 2% chance that the daughter virus will carry a mutated site from the parent virus.

  2. 75-80% is still a high percentage of deaths.

    1. yes it is! keep in mind, though, that even though ebola is so lethal, this is a virus that with the right precautions is not terribly infectious. SARS and the flu for example are much more infectious. Unfortunately ebola is striking a part of the world that is not sufficiently equipped to handle it properly and medical care is still in its infancy. That's the truly sad part. :-(

  3. As a scientist, I scoff at Ebolanoia and the hysteria in the US over this disease. But for reasons such as you describe here, I am concerned about where this epidemic is headed. For Africans, definitely a growing tragedy. For Americans and the rich West, I worry that what we think we know about Ebola virus may not be the whole story. And the genetic "story" is changing as the virus becomes ever more widespread.

    Still, the most important thing any American can do right now for their health with respect to infectious disease is GET A FLU SHOT.

    1. Unfortunately, often times, us westerners don't realize how lucky we are to have access to good medical care and vaccines. It should never be taken for granted (or refused, as is the case for vaccines).

  4. Thanks for posting this. I prefer facts presented in a logical manner that aims at informing rather than terrifying the reader. :-)

    Anna from Shout with Emaginette

    1. thanks, Anna! that's why I read papers instead of listening to the news! :-)


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