Cancer Drug Slows Poxvirus in Mice
Mice given a relatively new cancer drug can survive an otherwise
lethal dose of vaccinia virus, a relative of smallpox virus, report
scientists supported by the National Institute of Allergy and Infectious
Diseases (NIAID), part of the National Institutes of Health. The
findings, say the investigators, suggest that Gleevec or similar
drugs might be useful in preventing adverse side effects of smallpox
vaccine. The classic smallpox vaccine is made from live, weakened
vaccinia virus and is not recommended for people with compromised
immunity, except in emergency situations where they may have been
exposed to smallpox virus.
“This study helps illuminate the cellular machinery used
by poxviruses to exit infected cells, and also provides new support
for the concept of treating viral infections by targeting specific
host cell molecules rather than the viruses themselves,” says
NIAID Director Anthony S. Fauci, M.D.
The senior author of the paper, published online this week in
the journal Nature Medicine, is Daniel Kalman, Ph.D., of Emory
University School of Medicine in Atlanta.
Like all viruses, poxviruses co-opt various cellular molecules
and processes to enter a cell, replicate and then spread to uninfected
cells. Using lab-grown cells, Dr. Kalman and his colleagues identified
specific cell proteins vaccinia uses to detach from an infected
cell and move toward an uninfected cell. The proteins, members
of the Abl-family (pronounced “able”) of tyrosine kinases,
are well known to cancer investigators because mutation of one
family member, Abl, causes a rare form of cancer known as chronic
myelogenous leukemia (CML). Gleevec inhibits Abl-family tyrosine
kinases and has proved very useful in treating CML.
To learn whether Gleevec could prevent or lessen vaccinia’s
ability to spread in a living organism, the researchers treated
mice with either saline solution or with Gleevec at a dose equivalent
to that given to humans being treated for CML. Next, they exposed
the mice to ordinarily lethal amounts of vaccinia. All of the Gleevec-treated
mice survived, while 70 percent of the untreated mice died.
This finding, if confirmed in additional animal model studies,
suggests that Gleevec might play a role in addressing a public
health emergency in the event of a smallpox outbreak, Dr. Kalman
says. Specifically, Gleevec might be useful as a preventive against
adverse effects of smallpox vaccine, enabling clinicians to use
the vaccine even in people who otherwise could not take it. Given
for a short period, Gleevec theoretically could hamper the cell-to-cell
spread of virus and allow the body’s immune system to mount
a successful defense, he explains. Experiments to test whether
Gleevec might work against smallpox virus as well as against vaccinia
virus are now being planned, Dr. Kalman says. “The approach
of fighting disease by targeting drugs to cellular molecules rather
than to disease agents themselves may be applicable to a wide variety
of pathogenic microorganisms,” he says.
Routine vaccinations for smallpox ended in this country in the
early 1970s, and the World Health Organization declared smallpox
eradicated in 1980. Nevertheless, concern remains that smallpox
virus could be unleashed through an act of bioterror. For this
reason, scientists are working to better understand the mechanisms
of smallpox disease and to develop new and improved smallpox treatments
and vaccines.
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.
The National Institutes of Health (NIH) The Nation's
Medical Research Agency is comprised of 27 Institutes
and Centers and is a component of the U. S. Department of Health
and Human Services. It is the primary Federal agency for conducting
and supporting basic, clinical, and translational medical research,
and investigates the causes, treatments, and cures for both common
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visit www.nih.gov.
Reference: PM Reeves et al. Disabling poxvirus pathogenesis by
inhibition of Abl-family tyrosine kinasas. Nature Medicine DOI:
10.1038/nm1265 (2005). |