Increasing Manganese Levels Inhibit HIV

Scientists working with yeast have made the unexpected discovery that the metal manganese can block the replication of HIV inside cells, a finding that could lead to a whole new class of treatments for the virus, according to research released yesterday.

HIV depends on the enzyme reverse transcriptase to replicate, and a team of researchers at Johns Hopkins University in Baltimore found that higher than normal levels of manganese lower the activity of a similar enzyme used by a virus-like component of yeast. Further research determined increasing manganese levels also lowers the activity of HIV's reverse transcriptase, which could block replication of the virus and help prevent it from causing AIDS.

If drugs could be developed that increase manganese levels, it would be a novel approach to treating HIV, said Jef Boeke, professor of molecular biology and genetics at Johns Hopkins University and principal investigator of the study published in Molecular Cell (April 2002;9;4:879-889). Boeke cautioned, however, it is not yet known whether raising manganese levels in humans will have any therapeutic effect. HIV may still develop resistance but "a new class of agents would still be really useful because what has really been successful is combining drugs," he said.

The higher levels of manganese in yeast were caused by a defective gene called PRM1, which produces a protein that shuttles manganese out of cells. Carl Dieffenbach, associate director for basic sciences in the AIDS program at the National Institutes of Health's Institute of Allergy and Infectious Diseases, said the study will spur a flurry of research to further understand whether the PRM1 gene is a viable target to develop drugs around. "Within two to three years, we'll know if this is a viable target," he said.

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