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Susceptibility of mice to mousepox offers promise of smallpox protection

NOTE: This release has been updated since its original posting.

A team of scientists led by a Howard Hughes Medical Institute (HHMI) international research scholar has discovered the immune system mechanism that causes some mice to be more susceptible to mousepox than others. The discovery could pave the way to better protection for humans against the threat of smallpox, a related virus, as a weapon of bioterrorism.

HHMI international research scholar Gunasegaran Karupiah, a scientist at the John Curtin School of Medical Research at the Australian National University, and colleagues have identified proteins that determine which mice succumb to mousepox and which do not. The new insights into the immune response of mice to the mousepox virus could enable scientists to combine antivirals and cytokines such as such as gamma interferon to increase the efficacy of the treatment of poxvirus infections, including smallpox, said Karupiah.

The researchers found that strains of mice that are resistant to mousepox infection generate three types of the regulatory proteins called cytokines that are released by immune system cells to produce an immune response: interferon gamma (IFN-), interleukin-2 (IL-2), and tumor necrosis factor (TNF). Collectively, this is known as a type-1 cytokine response. Strains of mice susceptible to infection produce little or none of these cytokines, but they do produce IL-4--a type 2 cytokine. The findings were published online in the June 7 edition of the Proceedings of the National Academy of Sciences.

A potentially important application could be treating or protecting the increasing numbers of persons being vaccinated against smallpox with the vaccinia virus--primarily health professionals in the United States and elsewhere who are on the front lines of a potential bioterrorist attack.

"We are interested in not only overcoming an acute infection to save the individual, but at the same time hel
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Contact: Jennifer Donovan
donovanj@hhmi.org
301-215-8859
Howard Hughes Medical Institute
7-Jun-2004


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