Research Breakthrough Opens Door to New Strategy for Battling HIV

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.”