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New strategy for battling HIV

Date:
September 26, 2012
Source:
George Mason University
Summary:
New research shows how the HIV virus targets "veterans" or memory T-cells could change how drugs are used to stop the virus.

Researchers Yuntao Wu and Jia Guo in Mason’s National Center for Biodefense and Infectious Diseases.
Credit: Evan Cantwell

New research showing how the HIV virus targets "veterans" or memory T-cells could change how drugs are used to stop the virus, Mason researchers say.

The research will appear in the Journal of Biological Chemistry's October edition and currently is available online.

"It's a big breakthrough for us," says Yuntao Wu, an author of the study and professor at the Mason-based National Center for Biodefense and Infectious Diseases. "I think this will impact the field."

Helper T-cells support the body's immune system by organizing forces to fight off infection. The HIV virus hijacks helper T-cells. When helper T-cell numbers plummet, the body is vulnerable to disease.

Not all helper T-cells are the same; some are experienced ones called memory helper T-cells, and others, naive cells or "virgin" cells, haven't encountered an infection. Mason researchers studied why HIV preferentially goes after memory helper T-cells, while shunning their close colleagues. Memory and naive T-cells appear similar.

"In the body, HIV is able to kill most memory helper cells," says Weifeng Wang, PhD Biosciences '12, the study's main author. "We wanted to pursue what makes the difference between memory and naive T-cells on a molecular level."

Unlike naive helper T-cells, memory T-cells are on the go, and much more mobile. And it's that momentum that attracts the HIV virus and makes the memory cell vulnerable, says Wang, who's currently a research fellow in the Dana-Farber Cancer Institute at Harvard Medical School.

When a memory cell moves, inside the cell, it looks like a waterfall on the moving edge. "It's called 'treadmilling'," Wu says. "The cytoskeleton or the cell's supporting bone is acting like a muscle. The treadmilling of cytoskeleton pushes the cell to migrate. That's how it pushes itself. In the past year we've been studying how HIV infects those memory cells. It has to go to the center, into the nucleus. It has to go past the cytoskeleton barriers to go into the center. For many years we didn't understand how the virus could cross such a structure. It's like a wall. It has to cross that wall."

HIV jumps over the wall by exploiting the cell's treadmilling process, Wu says. "The HIV virus uses a receptor to attach to the cell for entry," he says. "When the virus touches that receptor it's like someone ringing the doorbell. That triggers a signal -- someone comes out and opens the door. Now the HIV virus can start the treadmill to 'walk' along the cytoskeleton towards the center. If the virus goes to naive cells, it cannot do it. Naive cells aren't sensitive enough. The cytoskeleton of these 'virgin' cells is different from the memory cells, and it is not easy for the virus to start the treadmilling process."

HIV's ability to mutate makes it difficult for our body to control it. "It can mutate very fast," Wu says. "You may have a lot of memory cell soldiers there but they are not able to recognize the HIV virus. They remember one guy, but this guy changes his face so they don't remember him. That's why our immune system is not effective against HIV. On top of that, the virus kills lots of your memory helper cells. Without sufficient help, your immune system is in complete dysfunction, and now you don't have an immune system."

HIV's knack for mutating makes it a tough target for drugs, Wang says. By shifting the focus to the cell, away from the virus itself, researchers may find a new way to tackle the virus, he says.

"Basically, our new strategy will be finding a cellular target, something HIV needs to depend on," Wu says. "It's as if the virus says 'give me a house.' The cell is the house. The house has to have electricity and everything so it can live there. Our approach is to look for something the virus needs to live in that house and then to reduce it or shut it down. The challenge will be if you shut that down, that it doesn't impact normal cell functions. It's a very tricky balance. You want to kill the virus but not healthy cells along with it."

Wu is looking at existing drugs, including those used for cancer. "There is something shared between cancer cells and HIV- infected cells because cancer cells also like to migrate. So some drugs that are used to slow down cancer migration could also be used to treat HIV."

As part of his doctoral thesis, Wang spent six years pursuing why HIV attacks memory cells. Failure is a part of research, he says. He had to change the experiment conditions multiple times before finding success. "It's like when you get lost in the woods at night; it's difficult to find the way out."

Mentors and colleagues spurred Wang on. Sheer persistence and hours in the lab eventually won out. "It's very challenging to do scientific discovery," Wang says. "There is no precedent."

NYC DC AIDS Research Ride partially funded the research for three years, Wu says. Also, a $1.2 million grant from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, is slated for the project from June 2009 until May 2013.


Story Source:

The above story is based on materials provided by George Mason University. The original article was written by Michele McDonald. Note: Materials may be edited for content and length.


Journal Reference:

  1. W. Wang, J. Guo, D. Yu, P. J. Vorster, W. Chen, Y. Wu. A dichotomy in cortical actin and chemotactic actin activity between human memory and naive T cells contributes to their differential susceptibility to HIV-1 infection. Journal of Biological Chemistry, 2012; DOI: 10.1074/jbc.M112.362400

Cite This Page:

George Mason University. "New strategy for battling HIV." ScienceDaily. ScienceDaily, 26 September 2012. <www.sciencedaily.com/releases/2012/09/120926133229.htm>.
George Mason University. (2012, September 26). New strategy for battling HIV. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2012/09/120926133229.htm
George Mason University. "New strategy for battling HIV." ScienceDaily. www.sciencedaily.com/releases/2012/09/120926133229.htm (accessed August 28, 2014).

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