Mice new frontier in HIV study

Posted on 12 Apr 2007 at 8:50pm
By John Wright Staff Writer

Dallas researchers make breakthrough in HIV research that could lead to major advances in prevention, treatment of virus



Dr. Anja Wege, a postdoctoral researcher at UT South-western Medical Center at Dallas, analyzes specimens. (Photo by John Wright/DV)

Until now, HIV research involving laboratory animals has focused almost exclusively on rhesus monkeys.

That’s because aside from chimpanzees, an endangered species, researchers have been unable to infect other animals with anything close to the human form of the virus that causes AIDS.

But rhesus monkeys are hardly an ideal model for HIV research, because they are expensive and difficult to house. Which is why a recent breakthrough at UT Southwestern Medical Center in Dallas could prove to be so important.

There, a team of researchers led by infectious disease specialist Dr. J. Victor Garcia has managed to rectally infect humanized mice with HIV, paving the way for what could be major advances in prevention and treatment of the virus.

“Nobody had ever been able to transmit HIV itself via natural route to a humanized mouse,” Garcia said. “It opens a multitude of doors that allow us to do types of experiments that were completely out of reach before.”

Future experiments involving humanized mice, which have been given the equivalent of human immune systems, could be geared toward developing everything from vaccines to microbicides, or preventive topical ointments, to post-exposure remedies, Garcia said.

“We’re limited by our imagination,” he said. “It’s very early to tell. The question is can we really do something with it, but I think it was a significant accomplishment.”

For the study, which appeared in the Journal of Experimental Medicine on Monday, March 26, Garcia and his team transplanted human tissues and stem cells into seven mice born without immune systems.

The mice developed high counts of pathogen-fighting human T-cells in virtually all tissues, including those critical to immune response, such as the guts and lungs.

Garcia and his team were then able to infect the mice with HIV rectally, which is the most common form of transmission between gay men, who account for 45 percent of people living with HIV.

“You can start asking questions that have relevance to the epidemic,” Garcia said.

Key among those questions is which of the multitude of viruses involved with HIV transmission actually take hold, Garcia said. If the strains are pinpointed, researchers can begin to develop microbicides and/or vaccines.

Mitchell Warren, executive director of the New York-based AIDS Vaccine Advocacy Coalition, called the breakthrough “exciting.”

Warren said rhesus monkeys have proven to be unreliable predictors of how potential vaccines will fare in humans.

“It’s an important step,” Warren said. “There isn’t one study that’s going to find an AIDS vaccine. It’s a series of activities and building blocks.”

Garcia’s is not the first research involving HIV and mice, according to Janet Young, program officer with the division of AIDS at the National Institute of Allergy and Infectious Diseases in Rockville, Md. However, previous studies have involved immuno-compromised mice implanted with only small amounts of human tissue before being injected with HIV.

Dr. Young agreed Garcia’s work is the equivalent of taking things to the next level.

“I think it sounds very good,” she said. “This looks to be a much more robust model for the human situation, so it should prove to be very effective.”

Other UT Southwestern researchers involved in the study were Michael Melkus, Anja Wege, Angela Padgett-Thomas, Paul Denton, Florence Othieno and Joel Gatlin.

E-mail wright@dallasvoice.com

This article appeared in the Dallas Voice print edition April 13, 2007

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