U of M scientists gain clues to stopping HIV

The ability of HIV to infect human cells and reprogram them into virus-making factories has frustrated efforts to combat the sexually transmitted infection for decades.

But University of Minnesota scientists have discovered clues about this process of "viral replication" that could improve treatment.

Using X-rays to analyze an Avian virus that resembles HIV, the researchers tracked how the virus creates enzymes called integrase that attack healthy cells and infect them with their own genetic material.

While other viruses arrange these enzymes in clusters of four to claw their way into host cells, the Avian virus surprisingly forms them in clusters of eight, according to the results, published Wednesday in the prestigious scientific journal Nature.

Understanding this process of viral replication gives researchers a better chance at creating effective medications, said Hideki Aihara, lead author of the paper and a molecular virologist at the university.

While existing antiretroviral drug cocktails include medications that inhibit integrase from infecting host cells, HIV can grow resistant to them.

"There are known mutations already against the current integrase inhibitors," Aihara said. "So it's really important to keep studying and trying to come up with new drugs."

HIV is no longer the killer it was 30 years ago — thanks to advances in antiretroviral medications — but it nonetheless is a severe, incurable infection that comes with a variety of risks and complications. Minnesota has reported about 300 new infections and 90 HIV-related deaths each year for the past decade. Roughly 8,000 people in the state carry the infection. It can be transmitted through needles or contact with certain bodily fluids, but sexual activity remains the leading form of transmission.

The so-called RSV virus in Aihara's study causes cancer in chickens and is genetically similar to HIV. As a result, researchers believe the findings could prove applicable to HIV infections in humans.

In the same issue of Nature, Salk Institute and Harvard University researchers report similar findings using an MMTV virus that causes tumors in mice. The studies are the second and third to identify molecular structures of retroviruses, and the results apply to more than HIV research, said Dmitry Lyumkis, a Salk fellow who co-authored the mouse virus paper.

Modified retroviruses have been effective in studies as "vectors" for delivering gene therapies to correct human genetic defects, Lyumkis said. But the way some of them integrate into the genome have caused cancers to form.

Mapping how retroviruses integrate is "quite interesting," he said, "in part for development of better and safer methods for gene therapy."

A next step for the researchers will be mapping HIV integrase enzymes to prove they work in the same way as the RSV and MMTV viruses.

The RSV work was painstaking, Aihara said. It took several years to create a crystalline form of the virus' protein complex for analysis, then another three years of number crunching with the help of the Minnesota Supercomputing Institute to confirm the precise positions of the molecules within the complex.

Researchers from Cornell and St. Louis universities collaborated in the project.

Jeremy Olson • 612-673-7744