Important note: Information in this article was accurate in 2002. The state of the art may have changed since the publication date.
Newsday - Monday, July 15, 2002
Laurie Garrett, Staff Correspondent
The finding concerns an obscure gene in HIV, an equally mysterious and poorly understood gene in human DNA and a way to suppress the ability of the virus to reproduce and infect cells. Taken together, the findings, which will appear in this week's issue of the British journal Nature, offer hope for both vaccine and drug makers.
For more than a decade Dr. Michael Malim, of St. Thomas' School of Medicine, Kings College London, has been studying an odd gene in HIV that has been dubbed vif. The role of the gene isn't understood, but when viruses lack it, or have a defective form of it, they are unable to infect other human cells. Lacking vif, a virus may replicate, but its progeny are unable to exit the cell of their birth, and thus are unable to infect other cells.
So, HIV without vif is essentially a harmless HIV.
But why?
In essence, Malim discovered that human cells possess an anti-HIV switch. But HIV with vif stifles that process.
Malim worked with an assortment of mutant HIVs that had defective or missing vif genes. In his search of the human genome for anything resembling a counterpart, he settled on a stretch of DNA that is the mirror image of the vif gene.
Malim found that HIV containing vif could replicate and infect in a normal manner. But if vif was absent, the DNA strand, dubbed CEM-15, seemed to exert a powerful effect, dramatically reducing the amount of viable viruses produced.
"I would characterize this as the most important discovery in HIV research since finding the cell receptors" that are used by HIV to gain entry to cells, Dr. Mario Stevenson, a viral gene expert at the University of Massachusetts in Amherst, said in an interview.
Already Dr. Ron Desrosiers at the New England Primate Center is in pursuit of the discovery's implications. When he uses vaccines created from vif-lacking HIV, monkeys develop an immune response without disease.
The discovery of CEM-15 "is a promising target for drug development," Malim said.
One question, of course, is exactly what purpose CEM-15 normally serves for human beings.
"It doesn't look like anything anybody has seen in the [human genome] database, ever," Malim said. "But CEM-15 hasn't just been hanging around in the human genome waiting for HIV to come along."
HIV is a member of a family of viruses, called lentivirus, which includes a number of pathogens that cause disease. One theory Malim is pursuing is that CEM-15 may be an ancient genetic switch in our DNA, aimed at protecting humans from this class of viruses. And only HIV has evolved this vif capacity to stifle the switch, allowing the virus to do its mischief.
At the just-ended International AIDS Conference, Dr. Melissa Farrow of the University of Massachusetts Medical Center described a patient infected with HIV for more than 20 years who had never shown any symptoms or signs of illness, despite having received no treatment. Farrow ultimately figured out that the patient's HIV strain had a vif gene, but the gene was defective. It would not get into the nucleus of human cells the virus infected, and therefore sat uselessly in the cellular cytoplasm.
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