A LONG-STANDING mystery about HIV has been solved 鈥� yet again. A team in New York claims to have found the elusive blood factor that allows some HIV-infected patients to stay healthy.
The work is important because it could lead to new treatments for HIV. But some experts say molecules already discovered account for much of the protective effect. Others insist we鈥檝e yet to identify the factor.
The hunt for the elusive factor dates back 16 years to a study done by Jay Levy鈥檚 team at the University of California, San Francisco. His team was studying HIV-positive people who didn鈥檛 get AIDS. They concluded that a certain type of immune cell in such individuals 鈥� the CD8 T cell 鈥� produces a small protein that helps them fight the virus. People who get AIDS don鈥檛 have this CD8 antiviral factor, or CAF.
Advertisement
But which protein was it? In 1995, Robert Gallo, who is now at the University of Maryland Biotechnology Institute in Baltimore, announced his team had unmasked CAF, at least in part. He concluded that it actually consists of three chemokines, small proteins that alter the behaviour of immune cells.
His theory got further backing when it was found that the chemokines bind to protein receptors that HIV uses to break into cells. That means the receptors may be occupied in people who produce chemokines, helping keep HIV out.
But this explanation didn鈥檛 satisfy Linqi Zhang and David Ho of the Aaron Diamond AIDS Research Center in New York. For one thing, Gallo鈥檚 chemokines only block a type of HIV called R5, which binds to the chemokine receptor CCR5. They don鈥檛 block another type of HIV, called X4, that binds to the CXCR4 receptor. CAF is thought to block both.
So together with colleagues at the biotech company Ciphergen in California, the researchers started looking for CAF using protein chips, a technology that separates and identifies proteins with great precision. They looked for proteins made by CD8 cells only, in three HIV-positive 鈥渘on-progressors鈥�.
They found a trio of small proteins which they identified as alpha-defensin-1, 2 and 3. Purified versions of these proteins inhibit both X4 and R5 HIV in human cells, they report in Science (DOI: 10.1126/science.1076185). Defensins are known to act as antibiotics by destroying the membranes of bacteria, but it isn鈥檛 clear how they fight HIV.
The researchers conclude that defensins account for almost all CAF activity against X4 viruses, and a substantial portion of the activity against R5, making it the best candidate yet for the elusive factor. 鈥淲e think we鈥檝e solved the puzzle of CAF,鈥� says Zhang. 鈥淚 think the data speaks for itself.鈥�
But others aren鈥檛 convinced. Gallo thinks that CAF is actually a mixture of proteins that may vary between people. Nonetheless, he says his work still suggests that 90 per cent of the activity against R5 viruses is due to chemokines. 鈥淭echnically, this a very sound paper,鈥� says Gallo. 鈥淏ut to say that all the CAF activity comes from defensins is absurd.鈥�
Levy insists that both groups have got it wrong. He believes neither chemokines or defensins are potent enough to account for CAF activity. But he does think the hunt is worthwhile: 鈥淚t鈥檚 gratifying to know people are finding all sorts of other natural antiviral factors, and that some of them might lead to a new type of therapy.鈥�