Paper in Cell describes how HIV uses a chemokine coreceptor CXCR4 molecule to activate the cofilin protein, which cuts through the cell’s cytoskeleton.
Scientists have determined that HIV uses a cell protein called cofilin to gain entrance to CD4 T cells. Their research found that when HIV binds to the cell surface, it uses the chemokine coreceptor CXCR4 molecule to send out a signal that activates cofilin.
The protein then cuts through the cortical actin cytoskeleton – the circular layer that lies just beneath the cell’s outer membrane – and allows the virus to enter human CD4 T cells.
“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,” says Yuntao Wu, Ph.D., assistant professor in George Mason University’s Department of Molecular and Microbiology. “For the virus, this layer also presents a barrier. 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.”
Dr. Wu and collaborators from the NIH analyzed CD4 T cells taken from blood and infected with HIV. He notes that though there is still much basic research left to be conducted before the team’s findings produce a clinical benefit, the discovery may later help develop a treatment that could block HIV’s viral interaction with the cortical actin cytoskeleton.
The findings will appear in the September 5 issue of Cell.
