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

Three-in-one antibody protects monkeys from HIV-like virus

September 20, 2017
A three-pronged antibody made in the laboratory protected monkeys from infection with two strains of SHIV, a monkey form of HIV, better than individual natural antibodies from which the engineered antibody is derived, researchers ...

Fighting HIV on multiple fronts might lead to vaccine

September 20, 2017
A combination antibody strategy could be the key to halting the spread of HIV, according to results from two promising animal studies.

HIV-AIDS: Following your gut

September 18, 2017
Researchers at the University of Montreal Hospital Research Centre (CRCHUM) have discovered a way to slow viral replication in the gastrointestinal tract of people infected by HIV-AIDS.

Study finds cutbacks in foreign aid for HIV treatment would cause great harm

August 30, 2017
Proposed reductions in U.S. foreign aid would have a devastating impact on HIV treatment and prevention programs in countries receiving such aid, an international team of investigators reports. In their paper published online ...

Cancer drug can reactivate HIV

August 24, 2017
People living with HIV must take a combination of three or more different drugs every day for the rest of their lives. Unfortunately, by following this strict treatment plan, they can suffer from side effects ranging from ...

New injectable antiretroviral treatment proved to be as effective as standard oral therapy

August 3, 2017
Intramuscularly administered antiretroviral therapy (ART) may be as effective for HIV treatment as current oral therapies. This is the main conclusion of a Phase II clinical trial carried out by 50 research centers around ...

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.