Scientists working with yeast have made the unexpected discovery that the metal manganese can block the replication of HIV (Human immunodeficiency virus) inside cells, a finding that could lead to a whole new class of treatments for the virus that causes AIDS (Acquired Immuno Deficiency Syndrome).

Human immunodeficiency virus depends on an enzyme called reverse transcriptase to replicate. A team of researchers at the 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 also lowers the activity of HIV's reverse transcriptase, which could block replication of the virus and help prevent it from causing AIDS.

The higher levels of manganese in yeast were caused by a defective gene called PRM1, which produces a protein that carries manganese out of cells. They expect the human equivalent of PRM1 will be a good target for drugs designed to treat HIV infection. If drugs could be developed that target PRM1 and increase manganese levels, it would be a new approach to treat HIV. The team is currently aiming for drugs that do just that.

Drugs that target PRM1 and increase manganese levels may help prevent the development of resistance. However, HIV may still develop resistance but a new class of agents would still be really useful. This study will spur a flurry of research to further understand whether the PRM1 gene is a viable target to develop drugs. The first step will be to do a study in mice. At the same time, researchers also can look at people infected with HIV and see if they can detect any with a defect in the PRM1 gene. If they do find a defect, they can determine if they are protected from HIV infection or have a slower progression of the disease. However, it is not yet known whether raising manganese levels in humans will have any therapeutic effect.

Molecular Cell April 2002, Vol. 9(4)