National Heart, Lung,and Blood Institute
Ebola virus is the most infamous of the hemorrhagic fever viruses, a group
of microbes found only in humans and monkeys. Although these outbreaks are
not common or widespread, they have received much publicity because of their
lethal nature and horrifying symptoms, which include high fever and massive
internal bleeding. To add to the mystery, Ebola virus strikes sporadically,
often devastating an isolated town or village before disappearing back into
the jungle, where scientists believe it may hide away in an as yet unknown
Ebola strains from Zaire, Sudan and the Ivory Coast are usually fatal to
humans, while a monkey strain that infected laboratory workers in Reston,
Virginia, in 1989 failed to cause overt disease. The reason for this
difference was not clear, but because Ebola virus produces several different
proteins, researchers believe one or more of these likely holds the key.
While studying these viral proteins, Zhi-Yong Yang and Gary Nabel, M.D.,
Ph.D., of the Dale and Betty Bumpers Vaccine Research Center (VRC), located
on the NIH campus, led a research team investigating glycoprotein (GP), a
sugar-containing molecule that sticks out from the surface of the Ebola
virus. Along with other scientists from the VRC, the National Heart, Lung,
and Blood Institute, and the Centers for Disease Control and Prevention,
Yang and Dr. Nabel discovered that a specific portion of the protein caused
it to destroy human and monkey endothelial cells in the test tube. The
protein also caused isolated blood vessels to leak, which may explain the
internal bleeding seen in infected individuals. GP isolated from the Reston
strain, however, destroyed only monkey blood vessels, possibly explaining
why this Ebola strain did not cause disease in humans.
As the scientists focused on GP, they found that a part of the protein that
becomes modified with sugars had a toxic effect on the virally infected
cells. When the researchers made forms of GP that lacked this region, the
protein no longer destroyed the blood vessels but was otherwise active. The
protein therefore serves two functions: it targets Ebola to the endothelium,
and once sufficient GP has been manufactured by the infected cells, it kills
those cells leading to the toxic effects of the disease.
By discovering the part of the protein that appears to be responsible for
Ebola-induced hemorrhaging, the researchers have made important strides
toward finding better ways to attack the virus. "We have been able to
define the major Ebola virus gene that kills cells, and have provided a
molecular target for potential new antiviral drugs and vaccines," states Dr.
Nabel. This study also begins to reveal the basic mechanisms of how Ebola
virus attaches to and enters cells, and future studies will continue to
investigate how different regions of the virus surface perform different
tasks for the invading microbe.
The Vaccine Research Center is a unique venture within the NIH intramural
research program that receives joint funding from the National Institute of
Allergy and Infectious Diseases (NIAID) and the National Cancer Institute
(NCI), and is spearheaded by NIAID, NCI and the NIH Office of AIDS Research.
NIAID is a component of the NIH. NIAID conducts and supports research to
prevent, diagnose and treat illness such as HIV disease and other sexually
transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is
an agency of the U.S. Department of Health and Human Services.
Press releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.
The National Institute of Allergy and Infectious Diseases
is a component of the National Institutes of Health,
U.S. Department of Health and Human Services