A London, Ont., virology lab has accidentally uncovered a link between 2 of history's best-known epidemics, AIDS and smallpox (Science 1999;286:1968-71). 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. FIGURE
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 it has been used to prevent land from being overrun by them.
"I think there will be more discoveries of viruses that use these receptors," Robarts virologist Grant McFadden told reporters. "Other viruses and pathogens may offer 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.
"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." The article reported that myxoma infection of CCR5 mouse cells could be inhibited by RANTES, a protein that normally binds to chemokine receptors, as well as by anti-CCR5 polyclonal antibody or herbimycin A. Pertussis toxin did not prevent infection, and neither did monoclonal antibodies that normally block HIV-1 infection. These findings raise hopes 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. The lab will continue its work on myxoma, but McFadden wants to collaborate with HIV researchers to uncover further implications of the findings.