Fighting HIV with HIV
Rajan, T. V., Natural History
In its zeal to keep competing viruses out of a cell it controls, the AIDS virus may have exposed its own vulnerability.
The acquired immunodeficiency syndrome, AIDS, has proved a challenging foe for medicine since it first became widely known almost a quarter century ago. Unlike most viral diseases, AIDS attacks more by stealth and by subverting the human immune system than by frontal assault. The virus that causes the disease enters a cell with the grace of an expert thief picking a complicated lock, using an array of the cell's sensors to its own advantage. Then the virus hijacks the machinery of the cell to reproduce-not in some violent orgy that leads to quick cell death, but patiently, quietly, spreading itself without raising much of an alarm.
Some of the world's best minds in biology have been working hard since the 1980s to define, design, and deploy a vaccine to prevent infection by the AIDS virus, and perhaps even to defeat the virus in established cases. Unfortunately, after the first rush of enthusiasm for such a strategy, many investigators have wondered whether a preventative vaccine is likely to appear in the next several decades, much less the next few years. The original model, or basic design idea, for such a vaccine, which goes back to the late eighteenth-century tactic the English surgeon Edward Jenner used to make the first smallpox vaccine, has proved unsuccessful so far.
But there are other options. One approach is summed up in an aphorism quoted by the first-century A.D. Greek writer Plutarch: "Knavery is the best defense against a knave." The knavery of the AIDS virus is twofold: its cunning method of infection-a large protein, which dangles from the virus like a hair, tricks a cell into Rising with it-and its insidious practice, once it gets inside the cell membrane, of adding its own genetic material to that of its host. (The latter action is what gives the AIDS virus and a number of other similarly acting viruses their name: retroviruses.) Those two behaviors are what have made the disease so difficult to combat.
The best defensive knavery against the AIDS virus may be to exploit one or both these tricks. Virologists now realize that the ongoing AIDS pandemic is not the first time a species of mammal has come under attack by a retrovirus. For example, investigators recently discovered a group of mice that is immune to a highly virulent retrovirus that infects the genomes of almost all other mice living in the area, and that does so via much the same mechanism as the AIDS virus uses to infect the human genome. Furthermore, it is now clear that about 8 percent of the human genome derives from other viruses that long ago spliced their genetic material into human DNA. Understanding the effects of those earlier viral encounters holds out the possibility that we can end AIDS's reign of terror.
Thinking about ths reign of AIDS, I still harken back to a day in 1982, when I was a young assistant professor of surgical pathology at the Albert Einstein College of Medicine, in New York City. The AIDS epidemic was just surfacing, and microscope slides prepared from fluid rinsed through a patients air passages had just come in to the hospital's department of pathology. Almost every member of the unit gathered to look at the slides.
Reviewing specimens with the pathologist is an important learning experience for every young physician. Most doctors, though, loaded with heavy clinical burdens, seldom have the time for such reviews. Most material a pathologist examines, after all, is fairly commonplace. But the occasional rare specimen is of great interest, and on that day in 1982, the specimen in the pathology lab was highly unusual and still so rare that most of us had never seen it before.
The Mobility and Mortality Weekly Report, published by the Centers for Disease Control and Prevention (CDC) in Atlanta, had recently alerted the medical community that, in the preceding several weeks, a number of patients with similar case histories had been arriving at hospitals in large urban centers, particularly Los Angeles, New York City, and San Francisco. …