Scientists render Ebola harmless

The deadly Ebola virus, an emerging public health concern in Africa and a potential biological weapon, ranks among the most feared of exotic pathogens.

Due to its virulent nature, a= nd because no vaccines or treatments are available, scientists studying the ag= ent have had to work under the most stringent bio-containment protocols, limiti= ng research to a few highly specialized labs and hampering the ability of scientists to develop countermeasures.

Now, however, a team of resea= rchers from the University of Wisconsin-Madison has figured out a way to genetical= ly disarm the virus, effectively confining it to a set of specialized cells and making the agent safe to study under conditions far less stringent than tho= se currently imposed.

"We wanted to make biologically contained Ebola virus," explains Yoshihiro Kawaoka, a professor of pathobio= logical sciences in the UW-Madison School of Veterinary Medicine and the senior aut= hor of a paper describing the system for containing = the virus published today (Jan. 21, 2008) in the Proceedings of the National Academy of Sciences. "This is a great system."<= /p>

The Ebola virus first emerged= in 1976 with outbreaks in Sudan and Zaire. There are several strains of the vi= rus, which causes hemorrhagic fever and during outbreaks kills anywhere from 50-= 90 percent of its human victims.

At present, research on live Ebola virus is confined to the very highest level of b= iosafety, known as Biosafety Level 4 (BSL 4). Because such laboratories are rare, small and very expensive, basic research that is the basis for any potential drugs or vaccines to thwart the virus has been limi= ted to perhaps half a dozen labs worldwide. The system devised by Kawaoka and his colleagues could provide a way to gre= atly expand studies of the pathogen and speed the development of countermeasures= .

Taming Ebola virus, according= to the new study, depends on a single gene known as VP30. Like most viruses, E= bola is a genetic pauper. It has only eight genes and depends on host cells to provide much of the molecular machinery to make it a successful pathogen. T= he virus's VP30 gene makes a protein that enables it to replicate in host cell= s. Without the protein, the virus cannot grow.

"The altered virus does = not grow in any normal cells," says Kawaoka. "We made cells that express the VP30 protein and the virus can grow in those cells because the missing protein is provided by the cell."=

It took years, Kawaoka explains, to find which viral protein was not= toxic to cells and could thus be used to develop a system, using monkey kidney ce= lls, to confine the virus.

And Kawa= oka, an internationally noted virologist, is convinced of the safety of the new system: "We did this work in a BSL 4, and the altered cells didn't pro= duce any infectious virus after many passages or replication cycles."<= /o:p>

With the exception that it is unable to grow in anything but cells engineered to express the VP30 protein, the virus is identical to the pathogen found in the wild, making it ideal f= or studies of basic biology, vaccine development and screening for antiviral compounds.

"This system can be used= for drug screening and for vaccine production," Kawao= ka says, noting that getting the equipment and compounds for such work into a = BSL 4 lab is extremely difficult. "High throughput screening (for drugs) i= n a BSL 4 is almost impossible."

Currently, live Ebola virus c= an be studied only in a BSL 4 laboratory. Any proposal to permit studying the pathogen in lower safety level labs is certain to generate controversy.

But according to Kawaoka, making the agent available for study to a br= oader cross section of science is essential for thwarting the virus that kills a = high percentage of its victims because there is now no defense against it. A new strain of Ebola, which so far has emerged only in remote areas of the world, was recently identified in Uganda and has killed at least 40 people.

"This = is an emerging virus and it's highly lethal," Kawaok= a says. "But because of the BSL 4 requirement, knowledge of this virus is limited."

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