Although most of the antibodies that the body produces to fight HIV are ineffective, some antibodies are produced that can neutralize HIV. To gain a better understanding of how these antibodies work, the researchers visualized the HIV spike bound to an antibody called b12 that can neutralize a broad range of HIV particles. The team showed that, in response to b12, the gp120 proteins rearrange in a similar manner as with CD4, but b12 prevents the spike from opening completely. The antibody locks the spike in a semi-open position, preventing the series of actions that enable HIV to infect the target cell.
"The insights gained by understanding the binding of one of the most effective broadly neutralizing antibodies lays the foundation for designing more effective strategies for blocking HIV infection," said Subramaniam. "We are working actively to increase the resolution of our structural analyses, and to understand the differences in binding between antibodies that neutralize, which are very rare in HIV-infected individuals, and non-neutralizing antibodies that are found in almost all AIDS patients. Knowing what these differences are will be critical to designing better strategies to neutralize HIV and to providing a new addition to the arsenal of strategies to combat HIV/AIDS."
The Subramaniam lab has been pioneering advances in electron tomography and related methods for three-dimensional electron microscopy, and is applying these emerging technologies to understanding not only virus-host interactions but also structures inside the cell that distinguish cancer cells from normal cells.
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Liu J, Bartesaghi A, Borgnia M, Sapiro G, and Subramaniam S. Molecular architecture of native HIV-1 gp120 trimers. Nature. Online July 30, 2008.
A diagram showing the structural changes in the HIV spike upon binding to target cell receptors is available at http://www.cancer.gov/images/newscenter/top.jpg and a video is available at http://www.cancer.gov/images/newscenter/schematic_spike_opening_380X380.mov.
For more information on Dr. Subramaniam's research, please go to http://ccr.cancer.gov/staff/staff.asp?profileid=5614 and http://electron.nci.nih.gov.
For more information about cancer, please visit the NCI Web site at http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).