New evidence supports a cofactor in AIDS.

New evidence supports a cofactor in AIDS

A controversial theory that primitive microbes called mycoplasmas play a contributory role in the development of AIDS got new support this week from one of its leading proponents.

Cultured cells infected with both Mycoplasma fermentans and human immunodeficiency virus (HIV) -- the virus causing AIDS -- die more readily than cells infected with HIV alone, according to a team of federal researchers headed by Shyh-Ching Lo of the Armed Forces Institute of Pathology in Washington, D.C. The finding, reported in the March 1 SCIENCE, supports a growing group of investigators championing the idea that mycoplasmas serve as cofactors in some cases of AIDS. Cofactors are independent organisms or molecules that act synergistically to foster or cause disease.

"When we coinfected cells with mycoplasma and HIV, the cell killing was much more dramatic," says Lo. "The implication is that mycoplasmas are important to the pathology of AIDS."

This research goes one step further than studies published last December by HIV-condiscoverer Luc Montagnier of the Pasteur Institute in Paris. They showed that antibodies against a particular piece of a mycoplasma's outer membrance could block HIV infection in the test tube.

Montagnier's studies were the first in vitro evidence that mycoplasma infections -- found one year earlier by Lo in the blood and tissues of AIDS patients -- could accelerate HIV disease. Both studies caused a controversy among retrovirologists, most of whom regard HIV as the sole agent responsible for AIDS (SN: 6/30/90, p.404).

The smallest and simplest organisms that can live without a host, mycoplasmas are strange microbes, now classified as bacteria. Most are innocuous, though some can cause pneumonia, premature labor or kidney disease.

To show that mycoplasma infection could worsen HIV disease, Lo and his colleagues infected separate cultures of human white blood cells -- called CD4 lymphocytes -- with HIV alone, with M. fermentans alone, or with a combination of the two. Cells infected with HIV alone at first died off to 20 percent of their original density, and then recovered to 80 percent after two weeks. But cells infected with both HIV and the mycoplasma nearly died off completely and they only recovered to 20 percent of their original volume within two weeks.

Thomas Folks, from the Retrovirus Diseases Branch of the Centers for Disease Control in Atlanta -- a former skeptic of the theory that mycoplasmas can accelerate AIDS -- finds Lo's new data persuasive. "I think Lo may be right . . . you have to believe that HIV is probably not acting alone," he says. But Folks adds he won't be convinced completely of the link until epidemiological studies show that most AIDS patients also have mycoplasma infections.

How might mycoplasmas aid and abet HIV infection? "At the present time we don't know the exact mechanism," Lo says. Cells infected with both mycoplasmas and HIV did not clump together to form giant, unhealthy cells called syncytia, as did those infected with HIV alone. They also did not test positive for reverse transcriptase, the enzyme HIV uses to reproduce itself. The assay is probably wrong, however, because mycoplasmas are thought to make a substance which could interfere with it.

Lo speculates that mycoplasmas may have an indirect effect on enhancing HIV infection. This might involve prompting cells to make such cytokines as interleukin-2 or interleukin-6 -- immune system stimulators known to activate HIV.

"I think that could be a real possibility," says Joseph Tully, a mycoplasmologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. "It's my gut feeling that there are cytokines involved in some way," he says. "It's certainly going to be investigated."