AIDS: long research road still looms ahead.

AIDS: Long research road still looms ahead

Three basic research reports provide useful insights into the AIDS-causing virus (HIV), but the news that emerges is not all heartening. In particular, one study suggests that an experimental drug called soluble CD4 appears less promising than once thought. Taken together, the three studies -- detailed in the Dec. 14 SCIENCE -- serve as a reminder that despite remarkable gains made by AIDS researchers in the past few years, the deadly virus they seek to understand remains insidiously difficult to manage.

In an encouraging report, molecular biologists describe isolating a piece of HIV's genetic code they hope to use in an AIDS vaccine. Scientists have had difficulty developing a vaccine that protects against all HIV strains because vaccine-induced antibodies that attack some strains prove useless against others.

With seven others, Kashi Javaherian of Repligen Corp. in Cambridge, Mass., vaccinated guinea pigs with a six-amino-acid sequence found on the outer coats of about 60 percent of HIV strains. The animals made antibodies that "neutralized," or rendered noninfectious, widely divergent strains of HIV bearing the key sequence on their viral coats. In earlier efforts, the researchers vaccinated animals with larger proteins that included the six crucial amino acids. But the surrounding amino acids apparently diverted much of the animals' antibody-making machinery away from the six key targets, says study coauthor Dani P. Bolognesi of Duke University Medical School in Durham, NC.

The new work suggests that a vaccine containing the six-amino-acid sequence and other proteins common to other HIV strains might provide broad protection against HIV infection in humans, Bolognesi says. However, he adds, it remains unclear just what or how many ingredients such a vaccine would require.

In a separate report, Dana Giulian and his colleagues at the Baylor College of Medicine in Houston describe an in vitro system that mimics the environment of an ADS-infected brain and may help scientists identify new treatments for AIDS-related neurologic damage. Researchers remain baffled by AIDS' central nervous system complications, which range from mild weakness to paralysis and dementia. HIV seems not to infect neurons directly. But the infection triggers an accumulation of white blood cells in the brain, leading some to suggest that these cells, called macrophages, may be inadvertent culprits.

The new in vitro system helps identify compounds secreted by HIV-infected white blood cells, and the tests the effects of those compounds on cultured neurons. Using the system, the Baylor team has identified a previously unrecognized neurotoxin secreted by HIV-infected macrophages. Moreover, Giulian says, their findings indicate that at least some AIDS-induced neuronal destruction occurs via one of the same biochemical mechnsms that cause brain damage during a stroke, suggesting that drugs useful for limiting the effects of stroke may someday play a role in minimizing the neurologic complication of AIDS.

In perhaps the most disappointing AIDS FINDING REPORTED THIS WEEK, researchers at the columbia University College of Physicians and Surgeons in New York City Showed that some viruses undergo mutations that enable them to circumvent an otherwise promising anti-viral strategy. Researchers had hoped they could prevent HIV infection in humans by flooding the bloodstream with engineered receptor molecules, called soluble CD4, that mimic the docking sites through which HIV enters cells. But Vincent B. Racaniello and his co-workers find that polioviruses can mutate in ways that prevent them from binding to soluble receptors while leaving them perfectly capable of infecting living cells. It's unclear how polioviruses manage this trick, or whether HIV can do the same, but the researchers say the findings "temper enthusiasm for the use of soluble receptors as antiviral compounds."