Editing Ebola – how to tame one of the world’s deadliest viruses

Blogging on Peer-Reviewed ResearchIn a list of the most dangerous jobs in the world, ‘Ebola researcher’ must surely rank near the top. But if new research is anything to go by, it may soon fall several places. An international team of scientists have recently found a way to neuter the virus, making it easy to study without risking your life. The altered virus looks like Ebola and behaves like Ebola, but it can’t kill like Ebola. It should make studying the virus easier and most importantly, safer.

Ebola virusThe Ebolaviruses and their cousins, the closely related Marburg family, have a chilling and deserved reputation. In some outbreaks, 90% of those infected die from massive blood loss. There is no approved antiviral treatment. There is no vaccine. And given that it’s almost a rite du passage for infectious disease scientists to contract the contagion they study, working with Ebola is a delicate affair.

Maximum protection

Ebola research requires the highest level of safety possible – the “Biosafety Level-4” laboratory. The stand-alone facilities are designed to be easily sealed and impervious to animals and insects. All routes in and out, including all pipes and ventilation, are peppered with multiple airlocks, showers and rooms designed to prevent any chance of escaping viruses.

There are very few people who are qualified to work in such a prohibitive environment and those that do have to wear a Hazmat suit at all times and breathe from a self-contained oxygen supply. No wonder then that the majority of Ebola research doesn’t actually use live, infectious viruses.

Scientists must instead settle with isolated proteins, proteins shoved into other, less harmful viruses or even “virus-like particles”. But these artificial systems are different to the virus proper, and using them is like staring at a complex machine through a cobweb-covered keyhole. Peter Halfmann from the University of Wisconsin has found a way around this, opening the door for scientists to get a proper look at the virus.

Editing Ebola

Ebola has a tiny genome that contains eight genes, which in turn provide the instructions for eight essential proteins. One of these – VP30 – is used by the virus to switch on its other genes and to make copies of itself.

Together with colleagues from the US, Canada and Japan, Halfmann cut out VP30 from the Ebola genome and replaced it with a gene for an antibiotic called neomycin. Without the gene, the virus is effectively castrated; it can’t carry out its normal deadly activities and it certainly can’t reproduce and spread to infect other cells.

To grow at all, it needs to be placed in a specially created culture of monkey cells that produce the missing VP30. These cells allow the virus to ‘come alive’ but they also act like a biological prison, containing Ebola by its own need for the all-important VP30.

Ebola plush toyUnder the electron microscope, the edited viruses were completely indistinguishable from their wild relatives in both size and shape. In the VP30 cells, they grew at a similar pace and produced their entire repertoire of proteins. But in normal cells, they completely failed to grow, and the team saw found not a trace of viral proteins.

Risks and benefits

There is, of course, a risk that the neutered viruses could somehow regain VP30 from the cells around them and regain their full infectious powers. Halfmann recognised this and carefully checked that the viruses were genetically stable. He was reassured – even after seven rounds of infection in the VP30 cells, the viruses retained the inserted neomycin gene and still failed to infect normal cells.

The implications for Ebola researchers are immense. Now, they have a virus that can be studied outside the prohibitive (and prohibitively expensive) confines of a biosafety level-4 lab.

They could replace VP30 with genes of their choice, such as GFP, a gene that produces a green, glowing protein that would make the virus easy to monitor. They could use Halfmann’s viruses to study Ebola’s life cycle in detail or screen thousands of potential anti-viral chemicals for new vaccines or treatments, in a way that is impossible with current artificial systems. When it comes to Ebola research, accept no substitutes.

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12 Responses

  1. Still sounds dangerous to me.. Even if one virus transposes VP30 back to its genome, you have an ebola outbreak…

  2. True, and I would assume the next step is to test the genetic stability more thoroughly. I also doubt that the endpoint of this will be people happily studying the virus in protection-less labs. But presumably even downgrading it by one biosafety level will increase the number of labs that can work with the virus?

  3. Hi Ed, yes I agree this is in fact great news putting the virus in a ‘biological prison’ will enable more labs to study it. But they should still be careful, viruses evolve fast and gaining that extra gene will be under positive selection :)

  4. No, there is no selection pressures here. The virus is being provided the gene, VP30. VP30 is now a host gene. It would be like Ebola virus picking up any other host gene into it’s genome. The virus can’t tell it’s missing it.

  5. That’s the right way! :)

  6. Sorry, I meant: a virus which gets VP30 can get out to invade other cells, which regular viruses cant, and that is a favorable selection making its generation more successful in replicating…

  7. Maybe I didn’t explain this clearly enough – the regular viruses have VP30. It’s Halfmann’s viruses that are the ‘irregular’ ones. If his strain somehow acquired VP30, it would then be exactly the same as normal Ebola strains and no more successful at replicating.

  8. George feels bad because the ebola came from his bum. The man in the yellow hat says monkies caused all the ebola and George is a monkey, but he has a yellow hat. So george is sorry for his ebola.

  9. [...] If you’ve ever read “The Hot Zone”, you know how frightening the ebola virus can be. Ed at Not Exactly Rocket Science discusses studying the virus in Editing Ebola – How To Tame One of the World’s Deadliest Viruses [...]

  10. Interesting research. Ebola has been a fascination of mine since reading The Hot Zone in 7th grade. I developed a need to read and research the virus to the point where my goal as a young 9th grader was to work for the CDC and study Ebola. Needless to say my parents thought I was nuts. I still keep up on the current research to this day even though I certainly don’t work for the CDC but took an alternative path into NICU nursing instead.

  11. Very interesting indeed. However, there are a lot more than 2 “level 4 biocontainment” labs in the US. I know from personal experience of 4 such labs. There may be only 2 run by the government, but there are many we don’t hear about, most located at major research universities.

  12. Thanks Martygrn! I got that information from the CDC website so it may well have been referring to Government-run facilities. I’ve amended the article accordingly.

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