Research breakthrough opens door to new strategy for battling HIV

September 26, 2012 by Michele Mcdonald
Researchers Yuntao Wu and Jia Guo in Mason’s National Center for Biodefense and Infectious Diseases. Photo by Evan Cantwell

(Medical Xpress)—New research showing how the HIV virus targets "veterans" or memory T-cells could change how drugs are used to stop the virus, according to new research by George Mason University.

The research will appear in the '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 and . "I think this will impact the field."

Helper T-cells support the body's immune system by organizing forces to fight off infection. The 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 ," says Weifeng Wang, 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 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 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 . 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 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 also like to migrate. So some drugs that are used to slow down cancer migration could also be used to treat HIV."

Explore further: New memory for HIV patients

More information: www.jbc.org/content/early/2012 … M112.362400.abstract

Related Stories

New memory for HIV patients

March 26, 2012
The hallmark loss of helper CD4+ T cells during human immunodeficiency virus (HIV) infection may be a red herring for therapeutics, according to a study published on March 26th in the Journal of Experimental Medicine.

Sugar-binding protein may play a role in HIV infection

June 14, 2011
Specific types of "helper" T cells that are crucial to maintaining functioning immune systems contain an enzyme called PDI (protein disulfide isomerase).

Under the right conditions, peptide blocks HIV infection at multiple points along the way

July 24, 2012
Human defensins, aptly named antimicrobial peptides, are made in immune system cells and epithelial cells (such as skin cells and cells that line the gut). One of these peptides, human neutrophil peptide 1, under certain ...

Recommended for you

Study suggests a way to stop HIV in its tracks

December 1, 2017
When HIV-1 infects an immune cell, the virus travels to the nucleus so quickly there's not enough time to set off the cell's alarm system.

Discovery puts the brakes on HIV's ability to infect

November 30, 2017
Viewed with a microscope, the virus faintly resembles a pineapple—the universal symbol of welcome. But HIV, the virus that causes AIDS, is anything but that. It has claimed the lives of more than 35 million people so far.

Rising levels of HIV drug resistance

November 30, 2017
HIV drug resistance is approaching and exceeding 10% in people living with HIV who are about to initiate or reinitiate first-line antiretroviral therapy, according to the largest meta-analysis to date on HIV drug resistance, ...

Male circumcision and antiviral drugs appear to sharply reduce HIV infection rate

November 29, 2017
A steep drop in the local incidence of new HIV infections accompanied the rollout of a U.S.-funded anti-HIV program in a large East-African population, according to a study led by researchers at Johns Hopkins Bloomberg School ...

Combination HIV prevention reduces new infections by 42 percent in Ugandan district

November 29, 2017
A study published today in the New England Journal of Medicine provides real-world evidence that implementing a combination of proven HIV prevention measures across communities can substantially reduce new HIV infections ...

Research on HIV viral load urges updates to WHO therapy guidelines

November 24, 2017
A large cohort study in South Africa has revealed that that low-level viraemia (LLV) in HIV-positive patients who are receiving antiretroviral treatment (ART) is an important risk factor for treatment failure.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.