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

By Ed Yong | October 18, 2010 9:00 am

Ebola

This is an old article, reposted from the original WordPress incarnation of Not Exactly Rocket Science. I’m travelling around at the moment so the next few weeks will have some classic pieces and a few new ones I prepared earlier.

In 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 by 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.

The 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.

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. 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.

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.

Under 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.

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.

Reference: Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1129-33. Epub 2008 Jan 22.

More on viruses;

CATEGORIZED UNDER: Medicine & health, Viruses
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