UNC-TV Science: Two Studies, Two Breakthroughs Against HIV

UNC-TV Science: January 17, 2014
Two Studies, Two Breakthroughs Against HIV

More than 33 million people worldwide currently live with HIV, the deadly virus that causes AIDS, which attacks the body’s immune system. Since the disease was first reported in 1981, medicine has come a long way in managing the deadly retrovirus, a virus that makes its DNA in host cells and uses those cells to multiply.

Antiretroviral therapies (ART) help to keep this virus and others like it at bay, but small hidden colonies of virus can escape ART, allowing the virus to come back. Also, we know the general mechanism of how HIV infects cells, but key parts of the biochemistry that could be used to stop infections in the first place are still unknown. But two studies, one from Duke and one from UNC Health Care, may help to solve some of these problems.

Viruses, at their most basic, are capsules made of protein that carry genetic information inside. In order for a virus to infect a cell, that protein capsule must help get that genetic information through the cell’s membrane to where it can force the cell to help it multiply, and at the point of attack usually sits a specialized protein that attacks the membrane.

In HIV, that protein is called gp41 and it has an open end that looks like a claw that opens up to attack the cell membrane. Scientists are interested in the membrane proximal external region, or business end, of gp41 as an area for a vaccine to attack so that HIV can’t get into the cells. The issue is that current imaging techniques require the molecules to sit still for a short time, and the business end of gp41 does its business too quickly for us to see its exact shape.

But a team of computer scientists and molecular biologists from Duke have found a way to get a picture of gp41. Leonard Spicer, Bruce Donald and Patrick Reardon worked together to design a whole protein that would stabilize the interaction between a cell membrane and gp41, and using a measurement technique that uses a bare minimum of data, they were able to create a picture of gp41 as it binds to a cell.

The work, which was published in the Proceedings of the National Academy of Sciences, may provide a specific target for a vaccine, and the Bill and Melinda Gates foundation recently donated $2.9 million for research into a vaccine that could stop HIV before it gets into cells.

Once HIV gets into cells, doctors can fight it with ART, but there are always a few infected cells which can “hide” from ART drugs, allowing the virus to recover and repopulate.

But a new study from UNC Health Care shows a new method that can target some of those cells that ART misses. The new treatment is a bound cocktail of an antibody (3B3), which recognizes HIV infected cells and a toxin harvested from bacteria called (PE38). 3B3 recognizes cells that are infected with HIV by recognizing a protein on their surface. After 3B3 binds to that protein, PE38 enters and kills the cell.

J. Victor Garcia, the lead author of the study, examined HIV-infected mice that had been genetically modified to carry human immune tissue. He gave them a treatment of three ART drugs at high doses, and that cocktail left some HIV infected cells every time.  Then, he gave those same mice the 3B3-PE38 compound, killing 5 of every 6 of the remaining HIV-infected cells. 

The treatment still isn’t perfect, but it does provide another weapon in the fight against HIV. The findings appear in the journal, PLoS Pathogens.

- Daniel Lane

Daniel Lane covers science, medicine and the environment as a reporter/writer. He is currently pursuing a master's degree in medical and science journalism at UNC - Chapel Hill.