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Rabbit-Test Hormone Suppresses HIV Genes in Mice

7 April 1997 8:00 pm
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A pregnancy hormone appears to protect newborn mice from a wasting syndrome that is similar to a hallmark AIDS symptom. The findings, in the current issue of the Journal of Clinical Investigation, suggest that one of the body's own chemicals might be a promising drug candidate against HIV.

AIDS workers have had few lucky breaks against the disease, but one is that, mysteriously, fewer than one in four children born to HIV-positive mothers is infected. Bolstering the theory that some factor during pregnancy protects against the virus is that HIV-positive babies appear otherwise healthy at birth and only later develop a severe wasting syndrome similar to that seen in adults in advanced stages of AIDS. A potential clue to the protective factor's identity came a few years ago, when test tube studies revealed that human chorionic gonadotropin (hCG), a hormone produced in the placenta during pregnancy, reduced levels of a key HIV enzyme in infected immune cells.

Probing this further, Abner Notkins and his colleagues at the National Institute of Dental Research in Bethesda, Maryland, studied the effects of pregnancy hormones on a mouse strain engineered to express several HIV-1 genes. Like HIV-infected human babies, newborn mice homozygous for the HIV-1 genes appear normal at birth but quickly develop dry, scaly skin and a wasting condition that results in death within a few weeks. The researchers implanted a tiny pump under the skin of lactating females 1 day after they had given birth and pumped into the females--and therefore into the milk the newborn mice drank--several hormones, levels of which are elevated during pregnancy: hCG, estrogen, progesterone, and dexamethasone. Only hCG had a protective effect: Indeed, the infusion prevented the newborn mice from developing the wasting syndrome. "These animals otherwise would have died," Notkins says. AIDS researcher Robert Gallo, of the Institute of Human Virology in Baltimore, reported similar, unpublished results on hCG's striking anti-HIV activity at the annual meeting of the American Association for the Advancement of Science (AAAS, which publishes ScienceNOW) in February.

Other experts point out, however, that it's unclear how relevant the mouse findings are to HIV-infected people. Moreover, mice don't appear to produce chorionic gonadotropin. "That clouds the interpretation," says one scientist who wishes to remain anonymous. Notkins's group is now trying to determine a mechanism for hCG's protective effects and is planning preliminary clinical trials in AIDS patients.

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