UF research could lead to more effective treatment for HIV


Published: Thursday, December 1, 2005 at 6:01 a.m.
Last Modified: Wednesday, November 30, 2005 at 3:08 p.m.
University of Florida researchers are working to close the doors of the body's cells to HIV invaders.
They've identified a biochemical code that a form of the human immunodeficiency virus, or HIV, uses to access immune system cells, turning them into virus-making factories.
In a study reported this month in the Journal of Virology, researchers suggest that new targets for treating HIV might be found by decoding the genetic makeup of the virus, which can pick a biochemical lock and break into cells called macrophages.
All strains of HIV-1, a strain of the virus that emerges in the later stages of the disease, can invade T cells, the body's infection-fighting cells also known as lymphocytes.
But they vary in their ability to enter macrophages, the long-living white blood cells often considered the scavengers of the immune system. The HIV-1 viruses that can infect both types of immune cells share a genetic lineage that allows them to chemically access macrophages through a series of ordered interactions at the virus's outer coating, or envelope.
"Most times when people think about HIV, they think about it infecting the T cells," said Maureen Goodenow, the study's senior author and the Stephany W. Holloway University Chair in AIDS Research at the UF College of Medicine. "When HIV enters the macrophage, it doesn't kill the cell, it uses it to create more virus. If we can stop that, we can stop the virus. Not kill it directly, but stop it from getting what it needs to complete its life cycle - a cell."
The key to halting the process would be to identify genetic biomarkers of HIV-1, Goodenow explained.
"With the biomarker, we can predict the virus's emergence over time," said Guity Ghaffari, the study's lead author. Ghaffari is an assistant professor of pediatrics in UF's College of Medicine.
The long-term goal of the team is to use the genetic information they collect to develop vaccine that doctors can use in combination with the antiretroviral drugs now used to treat AIDS.
This will be a fairly lengthy process, according to Goodenow.
"If we knew everything we need to know about the human immune system, we'd have an effective vaccine against AIDS by now," she said.
To identify how HIV-1 can enter macrophages, UF researchers took RNA and DNA samples from a group of 50 HIV-1 infected children and, through a series of steps, sequenced the DNA and analyzed the genetic makeup.
They found that a region on the surface of the virus, glycoprotein 120, dictates how viruses get into macrophages. To enter, the virus requires the presence of a molecule called CD4 and certain co-receptors, or "locks," CCR5 or CXCR4, on the macrophages' outer cell wall.
If the CD4 molecule is present, this type of HIV-1 virus can use it like a key to open the locks and enter the cell, said Goodenow.
"As it turns out, getting into macrophages is an incredibly complex interaction," she said. "In some ways that is good because if it were a very simple interaction, you'd have only one shot to break it up. But in this case you can have lots and lots of targets, interactions that perhaps scientists will be able to block."
Goodenow said the researchers ultimately would like to come up with small-molecule inhibitors which can interfere with the lock-and-key process that opens the cells to a virus invasion.
"Because we don't know the actual structure of the interaction, we need more studies to precisely localize where these interactions are occurring," she said.
People are living much longer with HIV, through combinations of drugs which have some serious side effects, Goodenow explained.
"The longer they are on these drugs, the more likely it is that the virus will develop mutations, and we are not making new drugs fast enough to keep up with that process," she warned.
With well over one million people infected with HIV in the United States alone, Goodenow said she and other researchers cannot afford to become complacent.
"The commitment to developing new drugs and vaccine strategies is absolutely essential," she said.
Diane Chun can be reached at (352) 374-5041 or chund@gvillesun.com

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