Researchers have long been intrigued, and a bit unnerved, by a family of microbes known as spuma or "foamy" viruses. These agents, which infect such diverse creatures as cats, cows, monkeys, hamsters and humans, are toxic to cells in a test tube. Yet infected animals often appear perfectly healthy-and the virus is so rare in humans that its effects are largely unknown. That could now be changing. Dr. W. John Martin, chief of immunopathology at the University of Southern California, has tentatively linked the mysterious microbe to an equally enigmatic illness: chronic fatigue syndrome (CFS).
At recent meetings of researchers and health officials, Martin has reported finding foamy virus in a number of patients with CFS, a persistent, debilitating, flulike affliction that has swept the world during the past decade. He also implicated the virus in a recent spate of severe, unexplained neurological illnesses. Few experts share Martin's belief that he's looking at a foamy virus. But four separate research teams are now finding evidence of an unusual viral infection among CFS patients, and there's a growing sense that they may be bearing down on the same suspect.
The search for a CFS virus heated up last fall, when Elaine DeFreitas, a virologist at Philadelphia's Wistar Institute, linked the illness to an unknown retroviral infection. Retroviruses are basically free-floating pieces of RNA that can translate themselves into DNA and splice themselves permanently into the chromosomes of host cells. (RNA, a single-stranded messenger molecule, is normally derived from the double-stranded DNA molecules that make up chromosomes, but retroviruses use a special enzyme to reverse the process.) Though animals carry myriad retroviruses, only a handful have turned up in humans. They include HIV-1 and -2 (the AIDS viruses), HTLV-l and -2 (the T-cell leukemia viruses) and HFV (human foamy virus).
Using a genetic probe-a strand of DNA that will bind to any matching strand hidden within a cell-DeFreitas discovered that blood samples drawn from CFS patients contained one of the four genes that make up HTLV-2. Yet the finding didn't implicate HTLV-2 itself, for the blood samples tested negative for a second piece of the virus. DeFreitas's hunch was that the patients harbored some related agent.
By the time DeFreitas reported these findings, Martin was pursuing similar evidence. He had been studying CFS in 1988 when local specialists started sending him patients with strange brain conditions. The first was a schoolteacher who, after deteriorating for nine months, was unable even to draw a picture of a clock. When Martin applied genetic probes to a sample of her brain tissue, he discerned an "atypical viral infection": the tissue tested negative for such likely suspects as herpes, but it responded to a general probe for retroviruses. He got similar results when he tested blood and spinal fluid from several other neurology patients. And when he ran the probes on 300 CFS sufferers, half of them tested positive as well.
Since last fall, Martin and DeFreitas have both succeeded at extracting a whole virus--not just a genetic marker--from CFS patients. Martin cites three reasons for thinking his is a foamy virus. First, he says, it looks like a foamy virus; viewed through an electron microscope, it has a spherical outer coat and resides mainly in vacuoles, or pockets, in the cytoplasm of cells. Second, it acts like a foamy virus, making cultured cells swell and stick together in large foamy masses. Finally, it reacts with probes made from simian foamy virus, a relative of HFV.
Other researchers nonetheless cite several grounds for skepticism. For example, the most distinctive feature of a foamy virus-a set of long spikes protruding from its outer coat-shows up only when the virus is spotted outside of a host cell. But Martin reported seeing only intracellular virus. Moreover, foamy virus is just one of several that can make cultured cells swell up and agglomerate. And as Martin is the first to admit, the genetic probes he used were not specific enough to provide a definitive identification. "What he's seeing sounds consistent with what I'm seeing," says DeFreitas, "but I think its identity is still open to question."
DeFreitas won't discuss her latest findings until they're accepted for publication. But her earlier work, suggesting that CFS involves a virus related to HTLV-2, has now been confirmed by researchers in Houston and at the University of Glasgow, in Scotland. Scientists at the U.S. Centers for Disease Control are also working to verify the retroviral connection. Dr. Walter Gunn, who heads the effort, sees "no reason to believe" it will fail. Linking CFS to an unusual virus won't allay the epidemic. No one knows whether the bug will turn out to be a cause or a cofactor in the illness. And even if a causal role is confirmed, the task will remain to figure out how the virus spreads-and how to stop it. But considering that just two years ago the medical world was dismissing CFS as a fantasy, there's been dazzling progress already.