Scientists Discover How Ebola
Virus Infects Cells
Finding Could Lead to Treatments for Viral Hemorrhagic
Ebola virus reproduction in laboratory-grown cells
is severely hampered by enzyme-inhibiting chemicals,
and these chemicals deserve further study as possible
treatments for Ebola virus infections in humans, report
scientists supported in part by the National Institute
of Allergy and Infectious Diseases (NIAID), a component
of the National Institutes of Health (NIH).
The researchers, whose paper is published online today
in Science Express, identified two cellular enzymes
Ebola virus must have to reproduce. When those enzymes
are blocked, the virus loses most of its infectivity,
the scientists found.
Ebola virus, like the Marburg virus now alarming Angola,
is a filovirus, a family of viruses that cause severe
and frequently fatal hemorrhagic fevers. “Finding medical
countermeasures for viral hemorrhagic fevers is a global
public health priority because not only do these diseases
occur naturally, but they also have the potential to
be unleashed by bioterrorists,” says NIH Director Elias
A. Zerhouni, M.D.
“This new research sheds light on the mechanism Ebola
virus uses to enter cells,” notes NIAID Director Anthony
S. Fauci, M.D. “These findings raise the possibility
of a broad-spectrum antiviral therapy that could be
effective against multiple hemorrhagic fever viruses.”
Senior author James M. Cunningham, M.D., of Brigham
and Women’s Hospital and Harvard Medical School in Boston,
and his colleagues discovered two cellular enzymes that
the Ebola virus co-opts and uses to cut up one of the
virus’ surface proteins. Once this protein is
snipped apart, the virus is free to begin multiplying.
The scientists applied broad-spectrum enzyme inhibitors
to mammalian cells before exposing them to Ebola virus.
When one specific cellular enzyme, cathepsin B, was
inhibited, the infectivity of Ebola virus dropped to
near zero. An accessory role is played by another cellular
enzyme, cathepsin L, the scientists determined.
Inhibitors of cathepsins are already under clinical
development as anti-cancer drugs. The authors write, “Further
investigation of the antiviral efficacy of [enzyme]
inhibitors may …be warranted. The wealth of existing
knowledge regarding the design and in vivo pharmacology
of these inhibitors may facilitate development of an
The work was done in collaboration with Nancy J. Sullivan,
Ph.D., of NIAID’s Vaccine Research Center.
The paper’s lead author, Kartik Chandran, Ph.D., of
Brigham and Women’s Hospital and Harvard Medical School,
is supported by a career development award from the
NIAID Regional Centers of Excellence for Biodefense
and Emerging Infectious Diseases Research (RCE) program.
In 2003, NIAID funded the establishment of eight RCEs
nationwide. The RCE program supports interdisciplinary
research aimed at new and improved therapies, vaccines,
diagnostics and other tools to protect against the threat
of bioterrorism and other emerging and re-emerging diseases.
NIAID is a component of the National Institutes of
Health, an agency of the U.S. Department of Health and
Human Services. NIAID supports basic and applied research
to prevent, diagnose and treat infectious diseases such
as HIV/AIDS and other sexually transmitted infections,
influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research
on transplantation and immune-related illnesses, including
autoimmune disorders, asthma and allergies.
News releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at http://www.niaid.nih.gov.