current research


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HIV and HIV-related proteins

In the past, a number of structures of HIV and HIV-associated proteins were determined by our laboratory, including Nef, Intergrase, Protease and Vpr. We also established a major program to investigate the interplay between HIV and cellular proteins.

The Pittsburgh Center for HIV Protein Interactions (PCHPI) is one of five centers funded by the NIH and dedicated to understanding HIV-host protein interactions at a molecular level.  The PCHPI is located at the University of Pittsburgh School of Medicine in the Department of Structural Biology.  Research conducted at the PCHPI is focused on a subset of early events in the HIV infection cycle, those that occur after the virus has fused with the cellular membrane and before the viral genome integrates into the genome of the cell. The path of HIV components and the cytosolic events that take place after membrane fusion and prior to nuclear import remain a poorly understood area of HIV biology.  At the same time, it presents an enormous opportunity for major discoveries.

A large number of interactions between HIV and host-cell components have been reported in the scientific literature. The PCHPI is dedicated to validating the functional importance of reported interactions and to determining high-resolution structures of HIV proteins and their interacting partners from the human host. Complexes are structurally characterized using a combination of X-ray crystallography, NMR spectroscopy, and electron microscopy. Furthermore, models and assays to predict and validate the biological significance of putative HIV-host protein interactions are being developed.  Results provide insight into aspects of HIV immediate post-entry biology and can be  leveraged to develop novel therapeutic strategies.

A particular highlight of work conducted at the PCHPI was the elucidation of an all-atom model of the HIV-1 capsid.