A Magazine for the George Mason University Community

Breaking the Code

By Mason Spirit contributor on April 1, 2009


Yuntao Wu

By Marjorie Musick

In a small lab on Mason’s Prince William Campus, Yuntao Wu and his team of researchers have spent the past six years decoding the molecular processes of the human immunodeficiency virus (HIV). As a result of one of his recent studies, the medical community is one step closer to understanding how HIV, the AIDS virus, attacks cells in the immune system.

“If you ask anyone working on AIDS why they are doing this, they will probably tell you that they want to cure the disease and help people. That is the ultimate goal,” says Wu, assistant professor in Mason’s Department of Molecular and Microbiology. “Once we really comprehend the basic mechanism of how HIV interacts with the body, then it may be possible to target and treat the infection.”

New Inroads in AIDS Research

In the September 2008 issue of the journal Cell, Wu and his collaborators from the National Institutes of Health (NIH) revealed the covert methods that HIV uses to break a barrier present in human CD4 T-cells, the primary immune cells targeted by the virus. HIV-1 infection causes CD4 T-cell depletion, which leads to immunodeficiency and AIDS.

During the six-year study, a team largely comprising research associates and graduate students analyzed CD4 T-cells taken from blood and infected with HIV. The researchers found that when HIV binds to the cell surface, it uses a molecule called chemokine coreceptor CXCR4 to send a signal that activates a cell protein known as cofilin. The protein is then used to cut through the cortical actin cytoskeleton (the circular layer that lies just beneath the cell’s outer membrane).

“Similar to a human skeleton, every cell has a cytoskeletal structure that supports the cell, gives it its shape, and provides a force that allows the cell to migrate. For the virus, this layer also presents a barrier,” says Wu. “We never understood how the virus overcomes this barrier to gain access to the center of the cell. Now we know that HIV triggers the mimicking of a cell process that activates cofilin, which cuts and modifies the cortical actin cytoskeleton and permits the virus to cross it.”

Wu notes that the goal of his research is to attain a fundamental understanding of how the virus interacts with cells and the immune system to identify new ways to treat the disease. Much basic research still needs to be conducted before the findings from this study produce a clinical benefit; however, Wu believes this discovery may later be used to develop a new treatment that could block viral interaction with or viral alteration of the cortical actin cytoskeleton.

“We are trying to develop a new therapy that will reduce the virus’ reservoir so that it will no longer be a living threat to the body.”

—Yuntao Wu

“Now we have a basic understanding of the parts that cortical actin and cofilin play in all this. This study really opened avenues for us, and we hope to use this information as a foundation for more detailed studies that could lead to the development of new therapeutic tools,” says Wu.

This research was largely funded by Mason. Additional support was received from the National Institute of Mental Health and the National Institute of Allergy and Infectious Diseases.

From Discovery to Development

Wu estimates that developing a new therapy typically takes 10 years from initial lab work to animal tests and clinical trials—and costs millions of dollars. Wu’s team is pursuing a new treatment based on a Trojan horse concept in which a particle that looks and behaves like the virus is used to target HIV-infected cells. The imposter particles then seek out and infiltrate cells containing a known HIV protein called “Rev.”

“The theory is that once these fake particles identify and invade infected cells, the Rev protein will trigger the release of a toxin that will eliminate the virus’ reservoir,” explains Wu. “So in this sense, it is just like a Trojan horse—it sneaks into the enemy’s territory and then jumps out and attacks.”

Yuntao Wu and

Wu with undergraduate biology major Anastasya Jabaly

What makes Wu’s research unique is his strategy of inducing the decay of HIV-infected T-cells so that patients may stop drug treatment without the virus rebounding.

“Right now, once the patient is put on therapy, it’s a lifetime treatment, arguably, because the current cocktail of drugs only inhibits the virus. Those blocks prevent HIV from spreading, but they are unable to destroy the virus’ resources,” says Wu. “We are trying to develop a new therapy that will reduce the virus’ reservoir so that it will no longer be a living threat to the body.”

The Path to Human Virology

Human disease was not always the subject of Wu’s investigations. He earned a doctorate in virology in 1998 from Queens University in Kingston, Ontario, Canada, after spending four years studying the DNA replication of the baculovirus family— a group of viruses fatal to insects that are often used for nonchemical pest control.

It was not until Wu joined NIH in 1999 that he began examining HIV infection in humans. “After four years of focusing on insect viruses, I really wanted to study human viruses so that I could see my work translated as a benefit to patients,” says Wu. “When I started at NIH, HIV was one of the biggest health threats facing the world, and I thought that maybe I could do something to help fight it.

A widely published researcher whose work has also appeared in prestigious scientific journals such as Science, Journal of Virology, Virology, Retrovirology, and Current HIV Research, Wu believes that a solution to the AIDS epidemic is possible.

“The more we understand the virus, the better we will be able to fight it,” he says. “Every time we discover something new in our lab, we really get excited because it brings us that much closer to finding a cure.”


No Comments Yet »

Leave a comment