Previous studies have shown that poxviruses such as smallpox, monkeypox, and vaccinia, the virus used to vaccinate against smallpox, all make proteins that bind to IFN- to interfere with its signaling pathway. Karupiah's findings bolster suspicions that IFN- and other cytokines play key roles in pathogenesis of these infections. He and his colleagues are the first to rigorously characterize the distinct cytokine responses in susceptible mice and compare them to those observed in resistant mice.

Many in the field had believed IL-4 to be a hallmark for a type-2 cytokine response, and IFN- to be characteristic of the type-1 response. Karupiah's group demonstrated that simply taking away IL-4 in susceptible animals is not by itself enough to reverse susceptibility, "meaning that it's a lot more complicated than people think," said Karupiah. "But the prerequisite for efficient virus clearance seems to be high levels of gamma interferon production."

Scientists know relatively little about the immune response to smallpox, primarily because the virus has been all but eradicated for years. Researchers and public health officials therefore had little motivation to understand the immune responses generated. Also, although Karupiah's group has been working with mousepox for 15 years, investigators worldwide have been generally wary of working with the pathogen for fear it might spread to other mouse colonies. "Smallpox was one of the biggest human scourges," said Karupiah, noting that in some populations there was a 30% mortality rate. "And yet, because it was successfully eradicated, no one was interested in understanding how individuals recovered. But now, of course, the interest is back because of the threat of bioter
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Contact: Jennifer Donovan
donovanj@hhmi.org
301-215-8859
Howard Hughes Medical Institute
7-Jun-2004