[procaare] 'AIDS Has Weak Link, One HIV gene may be key'

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'AIDS Has Weak Link, One HIV gene may be key'
[AEGiS](07.15.02)
********************

Barcelona, Spain - British researchers have discovered an Achilles heel of the AIDS virus
that scientists are hailing as one of the most significant pieces of good news to come
from the laboratory front in the battle against AIDS in several years.

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.

Source: [AEGiS] Study: AIDS Has Weak Link, One HIV gene may be key<mary@aegis.org>

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