UTMB research discovers what makes Ebola virus tick
Published 11:51 am, Friday, June 21, 2013
In September 1976, an alarming new virus appeared in central Africa. It started with flulike symptoms - fever, muscle pain, headache and sore throat - then progressed to vomiting, rash and internal and external bleeding. It spread rapidly, from patients at a hospital to their families and caretakers, and it killed almost 90 percent of the people who fell ill. By the time the outbreak subsided a few weeks later, nearly 300 people were dead.
That outbreak in Zaire - now the Democratic Republic of Congo - was the first recognized appearance of the Ebola virus. The disease, which took its name from Congo's Ebola River, hasn't been stopped since. In the 37 years since that first horrific wave, Ebola has become a steady source of fear in African countries. Outbreaks have flared up in Congo, in Uganda, in Gabon and elsewhere - and no one's found a treatment, a cure or a vaccine that works to stop it.
But in a high-containment lab at the University of Texas Medical Branch at Galveston, researchers have made a breakthrough that could lead to just that. They've figured out what makes Ebola able to shut down the immune system and run rampant in the body, and now they're working to find ways to counteract that mechanism.
The work is both personal and professional for Ndongala Lubaki, a postdoctoral fellow and the lead author of the team's paper, which was recently published in the Journal of Virology. Lubaki is a native of the Democratic Republic of Congo, and he was a young man living there when that first outbreak occurred.
"This is something that you know affects your people directly," he said, and that's what makes the potential for a treatment so important.
Ebola is such a deadly virus because it hampers the adaptive immune system, Lubaki said. Dendritic cells in the bloodstream would ordinarily trigger the immune system to respond, but Ebola prevents those cells from maturing and doing their job. So the body's disease-killing T-cells never get the signal to attack, the body's immunoresponse never kicks in, and the virus - unchecked - continues to harm the body.
This team of Galveston researchers, however, has located the "secret weapon" that helps Ebola short-circuit the immune system: two proteins that work together to shut down the dendritic cells and prevent the body from fighting back.
"We targeted some specific regions of the proteins and made some changes to the genetic code," Lubaki said. Those slight mutations created new strains of the virus, which the team then used to infect human dendritic cells in the lab.
And sure enough, these new viruses weren't able to suppress the dendritic cells' maturation. Which means, of course, the immune system has a fighting chance.
The discovery, Lubaki said, is "a first step." Now that they've found that secret weapon, they want to use that knowledge to help cure or prevent Ebola. One of the next steps will be testing possible treatments on animals.
Lubaki works in the lab of UTMB professor Alexander Bukreyev, which recently won federal funding for two major projects that involve Ebola. With a $3.5 million National Institutes of Health grant, the lab will work on developing an aerosol vaccine for the Ebola and Marburg viruses. The lab will study human immune responses to both viruses with the aid of a $1.8 million grant from the Defense Threat Reduction Agency, the U.S. Department of Defense's agency dedicated to countering weapons of mass destruction.
Ebola hasn't spread to people in the United States, but the ease and frequency of air travel means that is always a possibility - especially when there's an outbreak in a city with an international airport. Someone carrying the virus could fly to another country before Ebola's symptoms even appear.
"When there is an outbreak, you never know if that outbreak will reach a big city," Lubaki said. "If it does reach a big city, it can go anywhere around the world in a matter of days."
Diseases like Ebola, Lubaki points out, can also be used as biological weapons, which makes this research even more urgent.
"We need to have in our hands at least some form of treatment," he said.
But the immediate benefit will be seen in African countries, where Ebola epidemics occur regularly. In the past year, outbreaks in Uganda and Congo have killed dozens of people.
That's territory Lubaki knows well. In the 1980s, he started his research career in Kinshasa, investigating another virus that has impacted Africa: HIV. He moved to the United States in 1992 to continue his work at Johns Hopkins University. Three years ago, when he finished a Ph.D. at McGill University, Lubaki intended to return to Kinshasa to work on an HIV vaccine, but his immunology work led him instead to Galveston and the study of Ebola. It's another way of helping people in his home country.
"I'm always interested in what I call the science that makes sense for those who need it," he said. And the practical goal of a treatment for Ebola is a little closer now.
"There are armies of people working on the same subject," Lubaki said. "But at least you can do your part, hoping that someone will come up with some vaccine strategy or treatments."