Researchers Decode Viral Process that Prepares Cells for HIV Infection
Posted: September 5, 2008 at 1:00 am, Last Updated: November 30, -0001 at 12:00 am
With the publication of a study led by Yuntao Wu, assistant professor in Mason’s Department of Molecular and Microbiology, the medical community is one step closer to understanding how the human immunodeficiency virus (HIV) attacks cells in the immune system.
AIDS, which is caused by HIV, affected more than 33 million people worldwide in 2007, according to World Health Organization statistics.
In the Sept. 5 issue of the journal Cell, Wu and his collaborators from the National Institutes of Health reveal the covert methods that the virus 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 that leads to immunodeficiency and AIDS.
During the six-year study, a team largely comprised of 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 was to attain a fundamental understanding of how the virus interacts with cells and the immune system in order to identify new ways to treat the disease. There is still much basic research left to be conducted before the findings from this study produce a clinical benefit. However, Wu believes that 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.
“Now we have a basic understanding of the parts that cortical actin and cofilin play in all of 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. “For Cell to publish our findings is a great acknowledgment of the dedication and hard work demonstrated by my students and our group.”
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.