Next-Gen Sequencing Could Unlock Ebola’s Secrets, Yield Outbreak-Halting Clues

September 23rd, 2014
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The Ebola outbreak in West Africa has dominated recent newscasts and shocked many people with the speed and ferocity of its spread. Any such outbreak raises questions about its origin, its rate of transmission, and measures that can be taken to control its propagation. Thus far more than 2,600 people have died and the numbers are rising. There currently is no cure or treatment, notwithstanding recent high profile reports of experimental drugs and vaccines that are under development. In the absence of treatment, the main goal of healthcare workers is to care for the sick and to limit the spread of the virus. And fortunately, researchers are now also applying the latest technologies to search for new ways to halt Ebola.

 

In an effort to better understand both the virus and the current outbreak, Pardis Sabeti and colleagues at the Broad Institute/Harvard University, and the Sierra Leone Ministry of Health and Sanitation recently reported in Science the genomic sequence of 99 Ebola isolates that were collected from 78 patients in Sierra Leone during the first 24 days of the outbreak. Reviewing this information will ultimately help in the development of both diagnostic tests and drugs to better manage the virus. The Ebola genome is just under 20,000 nucleotides in length, encoding just seven genes. The apparent simplicity of the virus belies the havoc that is wreaked upon infection based upon an assault on the immune system and disruption of the blood clotting process, leading often to fatal internal bleeding.

 

Sabeti and colleagues found over 300 mutations among the 99 isolates. Such information reveals that:

 

  • The virus responsible for the current outbreak is different from, but closely related to the isolate responsible for the first recorded Ebola outbreak in 1976.
  • The virus mutates rapidly, which may complicate the development of diagnostic tests and drugs to treat the infection.

 

The high level of variability among the isolates should not be surprising since the replication of RNA viruses (which include Ebola, Influenza, and HIV) is typically error-prone. Several RNA viruses (including HIV) are known to accumulate mutations very rapidly, especially in cases where viral replication and spread are occurring rapidly as in the current outbreak. Many of the mutations observed by Sabeti’s team were found within protein-coding regions, suggesting they might affect the function of the proteins as well as the behaviour of the virus. Such mutations may affect virulence, viral replication, and the mode of transmission. Such mutations might also confer resistance to antiviral drugs that are under development or they could affect the accuracy and sensitivity of diagnostic tests. One lesson from the HIV epidemic is that combination therapies might be needed to sidestep the rapid accumulation of resistance-causing mutations.

 

The Science paper is a remarkable example of how modern genomic tools can be rapidly deployed to help tackle emerging threats. The first set of sequences were posted online only 12 days after the samples arrived from Africa. The second set required only seven days, because lab personnel worked around the clock to optimize the workflow. This is a remarkable testament to the current state of DNA sequencing and the dedication of scientists and healthcare workers seeking to halt the spread of infectious disease.

 

The sequencing of more Ebola isolates over the coming months will help investigators better understand how to reduce the spread of the virus. One of the next steps will be to deploy sequencing technology in West Africa to increase the rate of data collection. It is just a matter of time before technology advances to a state where sequencing can be done in remote areas using handheld devices. However, a massive effort that combines a combination of infection control, advanced technology, and better access to healthcare will be required to address the current challenge and to prepare for a world in which Ebola and other emerging threats will be ever more common.

 

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2 Responses to “Next-Gen Sequencing Could Unlock Ebola’s Secrets, Yield Outbreak-Halting Clues”

  1. Andreas Muehler says:

    Shane, there were reports that the infection rate is actually higher this time around since the mortality is slightly lower than at other outbrakes in the past, and hence the higher mortality made previous outbrakes a “self limiting” epidemic on a local level. Is there DNA evidence that can be linked to that?
    Andreas

  2. Shane Climie says:

    I don’t think that any sequence data yet correlate with changes in infectivity or pathogenicity. A colleague pointed out that there were more non-coding mutations than coding ones in the Broad study and that much remains unknown. It is certainly conceivable that mutations could affect the biology of the virus. It’s interesting to note the recent moratorium on “gain of function” research that could identify mutations that affect the transmission and other properties of various pathogens.

    Gain of function research was in the news in 2012 after researchers introduced mutations that enabled the avian H5N1 influenza virus to be transmitted directly between ferrets through the air. That led to a year-long moratorium on H5N1 research. Now, because of threats that include influenza, SARS, and MERS, the government is instituting a pause to gain-of-function funding for experiments involving these deadly viruses. It’s clear that dramatic changes in the pathogenicity of many deadly viruses might only be a few mutations away.