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, a study supported by NIH says.

The study, led by David Relman 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 of Health.

"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," Anthony S Fauci, director of NIAID says adding, "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" recently, set the stage for Dr. Relman's smallpox study. In this work, researchers at the US Army Medical Research Institute of Infectious Diseases, the Centres 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 defences. 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, the release says.

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" programme.