New Study on Smallpox in Monkeys Reveals Tactics of a Killer
Results of a new study in monkeys offer scientists a rare glimpse
of how, on a molecular level, the smallpox virus attacks its victims.
The findings shed light on how the virus caused mass death and suffering,
and will help point the way to new diagnostics, vaccines and drugs
that would be needed in the event of a smallpox bioterror incident.
The study, led by David Relman, M.D., of Stanford University, is
now online in the Proceedings of the National Academy of Sciences
(PNAS). The research was funded by the National Institute of Allergy
and Infectious Diseases (NIAID), part of the National Institutes
“In light of today’s concerns about bioterror attacks,
we have an urgent need to know as much as possible about the workings
of the smallpox virus and other bioterror agents,” says Anthony
S. Fauci, M.D., director of NIAID. “This new research fills
in some of the gaps in our understanding of smallpox. Now we are
better positioned to speed the development of protective measures.”
Related research, also published online in PNAS this week, set
the stage for Dr. Relman’s smallpox study. In this work, researchers
at the U.S. Army Medical Research Institute of Infectious Diseases,
the Centers for Disease Control and Prevention (CDC) and Stanford
University, show that cynomolgus macaque monkeys exposed to smallpox
virus can develop a disease similar to human smallpox. Previously,
scientists thought it impossible for the smallpox virus to sicken
any species other than humans.
Following on that discovery, Dr. Relman and a separate team of researchers
did molecular-level analysis of how the smallpox infection altered
gene expression patterns in the monkeys’ blood cells. Dr.
Relman used DNA microarrays, a tool unavailable in 1977 when naturally
occurring smallpox was eradicated after a global vaccination campaign.
Microarray analysis research reveals how smallpox alters gene activity
in host cells under attack by the virus. It also reveals changes
in levels of gene expression and expression of some proteins in
the blood of monkeys when they are infected with smallpox virus.
In their PNAS paper, Dr. Relman and colleagues suggest possible
mechanisms by which the virus subverts host defenses. Uncovering
these mechanisms gives scientists targets for developing countermeasures
to lessen or block the ability of the smallpox virus to cause disease.
Experts believe that this new knowledge of how smallpox acts on
cells could speed up development of smallpox countermeasures. Researchers
will now be able to compare the actions of smallpox on cells to
other pox viruses and use less lethal pox viruses in the search
for smallpox countermeasures.
CDC has the only U.S. laboratory facility in which research using
smallpox virus is permitted. However, many more labs in the United
States have sufficient safety features for handling less-lethal
pox viruses, such as monkeypox. If monkeypox — a pox virus
less virulent in humans — proves to have molecular workings
similar to smallpox, researchers could test countermeasures on it
in a greater number of lab facilities, hastening the pace of research.
NIAID supports research to develop animal models of monkeypox infection.
Researchers will evaluate the amount of virus needed to cause disease
by natural routes of infection such as inhalation, and the way in
which the disease develops. These models could potentially be used
to advance the development of diagnostics tools, vaccines and therapies
for smallpox without employing smallpox virus. NIAID is supporting
this research through its “In Vitro and Animal Models for
Emerging Infectious Diseases and Biodefense” program.
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
News releases, fact sheets and other NIAID-related materials are
available on the NIAID Web site at http://www.niaid.nih.gov.
References: KH Rubins et al. The host response to smallpox: Analysis
of the gene expression program in peripheral blood cells in a nonhuman
primate model. Proceedings of the National Academy of Sciences DOI:
PB Jahrling et al. Exploring the potential of variola virus
infection of cynomolgus macaques as a model for human smallpox.
Proceedings of the National Academy of Sciences DOI: 10.1073/PNAS0405954101.