Original Article TSG101 exposure on the surface of HIV-1 infected cells: implications for monoclonal antibody therapy for HIV/AIDS
Leyla Diaz, Hanwen Mao, Yu Zhou, Manu Kohli, Josephine Cassella, Zena Fesseha, Ke Weng, Hanson Chen, Douty Bamba James D. Marks, Michael Goldblatt, Michael Kinch
Functional Genetics, Inc. 708 Quince Orchard Road, Gaithersburg, MD 20878 USA Department of Anesthesiology, University of California, San Francisco, CA 94110 USA
Received July 8, 2010; accepted July 18, 2010; available online July 20, 2010
Abstract: HIV infection remains a major global public health problem, in part because of the ability of the virus to elude antiretroviral therapies. Most conventional drugs were designed to directly target virus-encoded mechanisms. However, there is increasing appreciation that certain host-encoded molecules are comparably important for the viral life cycle and could therefore represent potential antiviral targets. Prominent among these is TSG101, a cytoplasmic molecule that is “hijacked” by HIV and used to facilitate viral budding and release. In our present report, we demonstrate that TSG101 is uniquely exposed on the surface of HIV-infected cells and is available to antibody-based therapies. We also characterize the development of a monoclonal antibody, CB8-2, which reduces virus production from infected cells. These studies demonstrate the potential of TSG101-directed antibodies to combat HIV/AIDS. (AJTR1007002).