BASIC SCIENCE: HIV, Poxvirus Use Same Receptors - Brief Article

Applied Genetics News, Dec 19, 1999

A research team led from UC San Francisco and the University of Ontario reports in the Dec. 3rd issue of Science that myxoma poxvirus invades cells using the same chemokine receptors, CCR5 and CXCR4, which HIV uses. This finding may shed light on the origin of a rare mutation in the CCR5 receptor that has been found to confer immunity to the HIV virus in a small number of high-risk individuals. Genetic analysis has traced the likely emergence of the mutation to a major epidemic about 700 years ago--possibly the European smallpox plague.

Presumably the mutation was fixed in the population because it protected against smallpox infection. As the smallpox virus is no longer available to researchers, the theory cannot be tested directly. It is not known whether the poxvirus also uses the CD4 receptor, as does HIV. Apparently CCR5 is dispensable since individuals with the mutation remain perfectly healthy despite having inactive CCR5 receptors.

"This suggests a treatment or prevention strategy--blocking the CCR5 receptors to keep HIV out," suggests Alshad Lalani, Ph.D., a post-doctoral researcher at UC San Francisco and lead author of the Science paper. "There should be no ill effects."

Lalani and colleagues introduced the myxoma virus to a mouse cell line--normally not a target of myxoma infection--along with any of three human chemokine receptors--CCR1, CXCR4 and CCR5. They reported that any of the three chemokine receptors allowed infection by the virus--evidence that each functioned as a binding or entry receptor.

In a parallel set of experiments, researchers discovered that by introducing a high concentration of one protein, called RANTES, that normally binds to the human CCR5 receptor, they were able to prevent infection by the myxoma virus in mouse and primate cell lines. Presumably, this occurred because the protein occupied the CCR5 receptors and prevented the virus from gaining access. The discovery that the myxoma virus gains access through the CCR5 receptor may help in vaccine development, either for HIV or for other diseases, as poxviruses are commonly used as vectors for vaccines.