The Wake

An estimated 2,500 people in Minnesota are living with the HIV disease and do not know they have been infected.

In 2006, 318 new cases of HIV were reported in Minnesota, a five percent increase from the previous year.

Eighteen percent of these cases were reported among young people between the ages of 13 and 24.

A new case of the HIV disease is reported in Minnesota about every 27 hours.

These facts all come from the 2006 Profile of the HIV Epidemic from the MN AIDS Project, the most current look into virus data until the 2007 profile is published in April.

While these numbers may seem daunting or even frightening, they are not infallible. In fact, thanks to two assistant professors at the University of Minnesota, new fundamental discoveries are being made that may one day help lead to new treatments.

Dr. Reuben Harris and Dr. Hiroshi Matsuo, who both work in the department of biochemistry, molecular biology and biophysics, have recently solved the structure of a protein that is able to inhibit the AIDS virus HIV.

Their work began nearly three years ago “simply because we did not have an atomic picture of the DNA mutating protein with which we work — the human APOBEC3G DNA cytosine deaminase,” said Harris.

Working with a team of full-time researchers, the two used a technique called “nuclear magnetic resonance” to capture an image of APOBEC3G. Not only were they successful, but also the image was the first picture of any enzyme in its class.

While complementary studies have obtained genetic details about the protein “an atomic level understanding was lacking until we revealed the structure of the catalytic domain of APOBEC3G,” Matsuo says.

But this discovery is only one important piece of a much larger puzzle. Unfortunately, many prior studies have shown that a particular HIV protein, the virion infectivity factor, attacks APOBEC3G before it is able to deactivate the virus.

“This structural information will be therefore used by us and others to develop new therapeutic methods that protect APOBEC3G from Vif,” Matsuo says.

“The easiest to imagine will be a small molecule that only binds Vif, no other proteins within our bodies, and stops it from ‘seeing’ APOBEC3G,” Harris says.

But what really makes APOBEC3G so interesting? It is inside of all of us right now, Harris says.

“The most important concept to understand is that all people have this potent virus mutating enzyme, but it is normally degraded by the [Vif],” he says. “It is really a molecular war and we are working hard to help our protein win.”

While HIV is currently treatable using anti-retroviral therapy, a combination of three drugs, it is still without a cure. However, both Harris and Matsuo are confident that their work will contribute to the discovery of novel treatments.

“Many, many people including my team are working very hard to take fundamental discoveries and knowledge toward the development of novel and potentially better treatments,” Harris says.
Matsuo is also optimistic about virus treatment and predicts major changes for the near future.

“We expect to find low-molecular weight drug-like compounds that stop APOBEC3G degradation within three years,” Matsuo says. “Hopefully, these compounds will be turned into good drugs within an additional five years.”

While this discovery is monumental, as the doctors move closer to creating new drugs they may face even more complications.

Not only is the team in competition with dozens of institutions worldwide, according to Harris, but they may also have changes in patent law to worry about.

In a recent editorial in the Star Tribune titled “Threat To Invention,” Sally C. Pipes suggests that innovators may be less inclined to pursue their big ideas, especially those developing new drugs.

Pipes, president and CEO of the Pacific Research Institute, says that the Patent Reform Act would make it more difficult for inventors to obtain a patent, and more difficult to protect their work, even after obtaining a patent.

The act would require applicants to publish their ideas for up to 18 months before they know whether or not they have been granted a patent. This, Pipes argues, would allow others to view and potentially copy inventions.

Additionally, inventors would only receive patent protection for the particular elements of the invention that they created and not anything they improved or changed from an existing idea.

While these issues may be waiting somewhere in the future, right now Harris and Matsuo are focusing on the good things. Matsuo humbly stressed the support they received from their department on this project, and Harris, who recently returned from a curling tournament, was just as modest.

“We work very hard, but we are also having fun,” Harris says.