NERC-funded student helps analyse Ebola genome sequence

5 September 2014

A NERC-funded student has worked with an international group of researchers to help analyse newly available sequences of Ebola virus genome.

The virus, which is currently spreading through West Africa in the largest outbreak yet, has no known cure. Sequencing the genome and understanding the evolution of the disease may help researchers understand the disease and the risks it may pose in the future. Ultimately, this could help with vaccine development or therapies to treat the disease.

Ebola virus

Colourised transmission electron micrograph of an Ebola virus virion. Credit: CDC/Cynthia Goldsmith.

The vital work, published in the journal Science, describes how researchers from the Broad Institute and Harvard University in the US sequenced 99 Ebola virus genomes taken from 78 patients in Sierra Leone. Each sequence was made available online to the international research community as it was produced.

They produced the sequences to a high resolution using a process known as deep-sequencing - where the code is generated repeatedly until scientists can be highly confident in the results. This produced an extremely close-up view of the genome, which allowed the team to track the genetic changes the virus was undergoing within patients, determining how it spread through Sierra Leone and checking for changes to its protein sequences.

A vaccine targets proteins on the surface of the virus. Being able to see if these proteins have mutated could help other research groups develop a vaccine in the future.

The NERC-funded PhD student who contributed to the study, Gytis Dudas of the University of Edinburgh, conducted a phylogenetic analysis of the sequences to understand how the virus has evolved during the current epidemic. Ebola is a virus made up of a genetic material similar to DNA called RNA, which means it evolves rapidly - faster than the rate at which its hosts can develop any sort of immunity, making it hard to develop a cure.

"When we looked at the origin of the sequences, we noticed there are subtle differences between the sequences collected in Sierra Leone. We found three genetic clusters of the virus, which allowed us to track the virus as it spread through Sierra Leone. We could also ascertain that the outbreak there was caused by the same strain as the one in Guinea, where the outbreak began," explains Dudas.

The evidence suggests that the current epidemic stems from a single introduction of the Ebola virus into humans, before it began the subsequent spread through Guinea to neighbouring countries.

Phylogenetic tree diagram

Phylogenetic tree showing the descent of Sierra Leone strains from Guinea strains and the estimated dates of the beginning of the outbreak in West Africa and the introduction of the virus from Guinea to Sierra Leone. Credit: Gytis Dudas.

Dudas and his supervisor, Professor Andrew Rambaut, also of the University of Edinburgh, have already published a separate paper on the work in the journal PLoS Currents: Outbreaks, which gives clues about how the virus originally reached Guinea.

Their research showed that all of the viruses which have caused epidemics in the past have descended from a strain very similar to the one that caused the very first Ebola outbreak in the Democratic Republic of Congo in 1976.

"By analysing the sequences and producing genetic trees showing the branches of different genetic strains of the virus, we estimated that the virus causing the current outbreak, the West Africa outbreak, split off from the Central Africa outbreak in 2004," Dudas says. Although, he is quick to stress that this doesn't mean the virus reached West Africa at this point.

Bats are likely to be the natural reservoir for the virus, but scientists understand little about how the virus is evolving among them.

The team is now working to acquire the sequences of a different Ebola strain which is causing an outbreak in the Democratic Republic of Congo.

"The Congo strain is unrelated to the strain in West Africa, so that outbreak gives us another glimpse into what's going on in the virus reservoir. Without more sequences, especially sequences from the bat reservoir, there is very little we can tell about how the virus is moving through Africa, and whether the current outbreak was preventable, since we are completely reliant on samples from infected humans," Dudas concludes.

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1. Paper references:

Press release: 23/14