Medicine: AIDS Research Spurs New Interest in Some Ancient Enemies

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Unlike any other known creature, the virus occupies a strange netherworld somewhere between living and inanimate objects. While made up of protein and genetic material, it lacks the cell structures common to all life. And unlike true lifeforms, it does not need and cannot metabolize nutrients, does not grow, and cannot replicate without the help of its host. Says David Baltimore, head of the Whitehead Institute in Cambridge, Mass.: "Viruses are the most extreme form of parasite." Anthony Faras, director of the Institute of Human Genetics at the University of Minnesota, emphasizes the virus' utmost dependence on its host. "Put a virus in a test tube," he says, "and it can't do anything. It can't even make copies of itself."

To circumvent its shortcomings the virus must commandeer the protein-making facilities and cellular power plants of its host. It does so by staging a genetic coup, either inserting its genes into the DNA of the host cell -- as the AIDS virus does -- or establishing a floating command center either in the nucleus or the cytoplasm. Once activated, the viral genes order the cell to begin producing more viruses, carbon copies of the original invader (see chart).

In general, viruses are particular in choosing their hosts. Though some, including the rabies and flu viruses, are capable of infecting both animals and man, most favor not just a single species but a limited number of cell types within that species. "If it's AIDS, it commonly goes to the T cells," says Dr. Bernard Fields, chairman of the department of microbiology and molecular genetics at Harvard. "If it's polio, it goes to certain subsets of nerve cells in the spinal cord. If it's hepatitis, it goes to the liver." Until recently the virus' ability to discriminate mystified researchers. How, after all, does a rabies virus, entering the muscle tissue through a dog bite in the leg, know how to find its way along the nerves to particular cells in the brain? The answer lies in the configurations of both the invader and the cell it targets. The rabies virus carries a protein on its envelope shaped in such a way that it meshes precisely with another protein, or receptor, found on the surface of certain brain cells, just as AIDS virus surface proteins fit helper T cell receptors.

Nature did not provide these docking sites for the convenience of viruses; they serve as receptors for hormones and other substances vital to the workings of the cell. It is the peculiar genius of viruses that they have mutated and evolved protein shapes that enable them to use these receptors as ports of call. Once the virus has docked, it is taken in as if it were a valued visitor. "This is a lovely event," says Harvard Biochemist Stephen Harrison admiringly. "The virus gets taken into (the cell), and pow! -- the genes of the virus are dumped into the cytoplasm." In the typical acute infection, like the common cold or the flu, those genes go straight to work, producing proteins that eventually take over and retool the cell machinery to make viruses.