Fighting HIV with HIV: in its zeal to keep competing viruses out of a cell it controls, the AIDS virus may have exposed its own vulnerability

Gardner and his colleagues became interested in retroviral infections among feral mice. In a barn on a squab farm near the town of Lake Casitas, California, they found a colony of mice in the throes of an epidemic. A particularly virulent retrovirus was spreading to young mice as they nursed. Yet within the closed population, some of the mice were clearly resistant to infection. Investigators analyzed the genomes of both the resistant and susceptible populations and quickly identified a stable, heritable genetic locus in the former group that was not present in the latter.

Molecular cloning of the locus showed that it carried a highly mutated form of the DNA copy of the retroviral genome infecting the colony. The data implied that within the group of virus-resistant mice, at least one founder had carried so many viruses in its bloodstream that the viruses were infecting other tissues, including germ cells. By the time the virus had become stably integrated with the germ-cell DNA, however, the virus had mutated, and so the mutated form was being passed along to the mouse progeny, just like the rest of the mouse genome.

The cells of these virus-resistant mice produced no viral particles. Instead, the cells produced just the viral proteins that would block the receptor molecules used by the viruses on the mouse cells, preventing complete, infectious viruses from entering. Even though the mice were presumably heavily exposed to the virus present in the barn, the defective copy of the virus they inherited was keeping new, lethal viruses out of their cells and protecting the lucky mice from the ravages of the disease.

The Lake Casitas mouse colony offers an outstanding example of how evolutionary forces might deal with viral infections. Given the efficacy of the process, a number of investigators have begun to wonder whether a similar approach might work against HIV.

Donald B. Kohn and his collaborators at the Children's Hospital Los Angeles have been investigating the possibility of inoculating white blood cells such as T cells against HIV. White blood cells, red blood cells, and platelets are generated by a kind of stem cell in the bone marrow that displays a molecule called CD34 on its cell surface (the molecule lends its name to the stem cell as well). Infecting CD34 cells with defective HIV might offer an elegant way to treat people already infected with HIV.

Many leukemia patients and others have survived a medical procedure known as a bone-marrow transplant. In that procedure, the patient's marrow is irradiated to kill cancerous cells, and then non-cancerous stem cells from a donor are restored to repopulate the bone marrow. A similar treatment could help AIDS patients. If some of the CD34 cells were removed before irradiation and infected with defective copies of HIV, they could then be replaced after irradiation. As the replaced cells repopulated the bone marrow, they would give rise to T cells that also carried the genetic instructions for making defective HIV.