A team of Harvard researchers has developed a new portrait of how HIV, the virus that causes AIDS, reproduces itself in a development that may provide clues for future drug treatments.

Through a collaboration between the Department of Chemistry and Chemical Biology and the Department of Molecular and Cellular Biology, researchers were able to take a snapshot of a stage of the mechanism by which the enzyme reverse transcriptase (RT) works on a strand of viral DNA to make new copies.

Understanding this mechanism may help researchers make new drugs that will serve as options in the drug cocktails--mixtures of three or four drugs--that have resulted in far more effective treatment of AIDS.

RT, one of several major proteins in the AIDS virus, is one of the most important enzymes in the replication of HIV, performing various functions at different stages of replication.

Currently, one major class of drugs that fights AIDS, called RT inhibitors, tries to interfere with RT. These drugs range from AZT to DDI to DDC.

But mutations in RT--which lead to mutations in HIV--sometimes make these drugs ineffective, said Huifang Huang, a post-doctoral fellow in the Department of Molecular and Celluar Biology who served on the research team.

"The virus finds a way to evade the action of the drugs that we come up with to fight it," said David D. Ho, a Harvard Overseer who won Time Magazine's Man of the Year Award in 1996 for AIDS research.

With an understanding of the mechanism, researchers said they have made another important step in combating AIDS, which killed 2.3 million people worldwide last year.

Higgins Professor of Biochemistry Stephen C. Harrison, who worked with the research team, said that while this is not "some major breakthrough...in the history of AIDS research," it is certainly an advance.

"Here's one more small step in the direction of trying to make this process faster, better, more rational, more effective," Harrison said. "[And] it's a contribution I'm very proud of, incidentally," he added.

"That's how science is done," Ho said. "Little by little."

A Good Shot

The group's research, published in an article in Science entitled "Structure of a Covalently Trapped Catalytic Complex of HIV-1 Reverse Transcriptase: Implications for Nucleoside-Analog Drug Resistance," represents years of efforts aimed at understanding RT.

In the late 1980's Harrison and colleagues at other schools began uncovering the structure of RT. But until recently, researchers still did not know much about the mechanisms by which RT worked.

Then several years ago, Harrison joined forces with Professor of Chemistry Gregory L. Verdine and Huang. Rajiv Chopra, another post-doctoral fellow, joined the effort soon after.