Researchers link AIDS resistance and smallpox

Date: Dec. 3, 1999
Time: 12:17 pm

The researchers, who originally worked at the John P. Robarts Research Institute (some have since moved to other centres) found that myxoma virus (a rabbit-specific poxvirus related to human smallpox) uses the same chemokine receptors as HIV to infect immune cells. This is the first time that a virus other than HIV has been shown to exploit chemokine receptors.

In a paper (Science(registration or subscription required) published today, the research team reported that 3 human chemokine receptors, CCR1, CXCR4, and CCR5, all induced infection when mouse cells were exposed to the myxoma virus, which is so lethal to rabbits that officials in Australia and New Zealand used it during the 1950s to prevent agricultural land from being overrun by rabbits introduced from Europe.

"I think there will be more discoveries in the future of viruses that use these receptors," Robarts virologist Grant McFadden told reporters yesterday. "This is just the tip of the iceberg. Other viruses and pathogens may open other insights into these receptors."

Because of the involvement of chemokine receptors in inflammation, the discovery will also affect researchers in that field, McFadden added.

The Canadian findings may also provide an explanation for the 1% of Caucasians who are immune to HIV infection. It is known that such immunity involves a genetic defect involving chemokine receptors. Perhaps resistance to HIV developed many centuries ago during epidemics of smallpox, the most lethal virus in the history of medicine, he said.

"The protective mutation in the CCR5 chemokine receptor gene almost certainly emerged well before HIV began to infect humans, just about 50 years ago," said Alshad Lalani, lead author of the Science article. "Based on genetic analysis, it has been speculated by HIV researchers that the CCR5 mutation probably evolved at least 700 years ago, possibly during the European smallpox plagues," Lalani said in a written release. After participating in the discovery at Robarts, Lalani went to the University of California's San Francisco campus, where he is now involved in postdoctoral research. The Science paper reported that myxoma infection of CCR5 mouse cells could be inhibited by RANTES, a protein that normally binds to chemokine receptors, as well by anti-CCR5 polyclonal antibody or herbimycin A. Pertussis toxin did not prevent infection. Neither did monoclonal antibodies that normally block HIV-1 infection. These findings raise hope that some form of 'blockade' therapy might be possible, McFadden said.

The discovery in McFadden's laboratory was an accidental byproduct of research into chemokine inhibitors expressed by the myxoma virus. The lab will continue its work on myxoma, but McFadden wants to collaborate with HIV researchers to uncover further implications of the new findings.

In a nice coincidence, publication of the Science article coincided with McFadden's 50th birthday.

-- David Helwig, London, Ont.

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