Research team develops nonhuman primate model of smallpox...( bination of aerosol plus intravenous in...)

Both variola strains produced severe disease, with almost uniform lethality and end-stage lesions resembling the human disease, in monkeys exposed by the combined route of infection. According to the authors, death usually occurred within six days of inoculation. Similar results were seen in monkeys that received the same dose of either virus by the intravenous route alone.

Having demonstrated that it was possible to achieve lethal infection of primates using variola virus, the team next tried to determine whether lower doses of virus would produce a less accelerated disease course. In order to more closely mimic human smallpox, the animal model would include near uniform mortality, but a longer mean time to death. Using a ten-fold lower dose, however, also resulted in lower mortality overall, so further refinement of the model is indicated.

"Despite its limitations," the authors wrote, "the intravenous variola primate modelhas already provided valuable insight into the pathogenesis of this exquisitely adapted human pathogen." In a related article in the same journal, Rubins and her colleagues examined the host gene expression patterns of hemorrhagic smallpox in these animals. Specifically, they documented fluctuations in cellular proliferation, interferon, and viral modulation of the immune response. A better understanding of the disease process that occurs with smallpox infection will aid in the development of diagnostic and therapeutic approaches.

"Aside from the technical accomplishments, what's notable about these studies is the collaboration between multiple agencies--including the Department of Defense and the academic sector--to address the issues raised in the 1999 Institute of Medicine report on the need to retain live variol
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Contact: Caree Vander Linden
Caree.Vander-Linden@det.amedd.army.mil
301-619-2285
US Army Medical Research Institute of Infectious Diseases
4-Oct-2004