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Elevating Manganese Levels hold back HIV

According to researchers at the Hopkins University, working with yeast have made the unexpected discovery 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 that causes AIDS.// A team of researchers at Hopkins University in Baltimore found that, human immunodeficiency virus depends on an enzyme called reverse transcriptase to replicate, and 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 acquired immune deficiency syndrome.

According to Jef Boeke, professor of molecular biology at Hopkins University, if drugs could be grown that increase manganese levels, it would be a innovative approach to treating HIV. Boeke said his team currently is looking for drugs that do just that. 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. The Hopkins scientists, felt that they human equivalent of PRM1 will be a good target for drugs designed to treat HIV infection. Boeke cautioned, however, it is not yet known whether raising manganese levels in humans will have any therapeutic effect.

One of the first treatments for HIV infection, the antiretroviral zidovudine (AZT), targeted reverse transcriptase. The virus is notorious for developing resistance to drugs, however, so new treatments are needed to keep it in check. Drugs that target PRM1 and increase manganese levels may help prevent the development of resistance, Boeke said.

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.

Carl Dief
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