The HARC Center is an interdisciplinary research center aimed at creating a comprehensive structural picture of interactions between HIV viral proteins and intracellular host molecules at early stages in the viral lifecycle. High-resolution structures of such complexes offer the potential for novel targeted drug design strategies in the treatment of AIDS.

Virus-host complexes play essential roles in HIV infection and propagation. Host T cells are initially targeted by the binding of viral proteins to cell surface receptors, and once internalized, the virus depends upon a different set of interactions with intracellular host proteins for the successful production, packaging and release of new viral particles.

The HARC Center is specifically focused upon five HIV proteins that perform essential regulatory and acccessory functions at this stage: Integrase, Tat, Rev, Vif and Nef. Integrase coordinates with host proteins to integrate a DNA copy of the viral genome into the host genome, while Tat and Rev recruit cellular proteins to enhance the production and nuclear export of viral mRNAs. Vif is a component of an assembly that tags host defense proteins for destruction, while Nef interacts with a variety of proteins to remodel cell architecture and alter signaling, enhancing viral replication overall.

The Center aims to provide a detailed structural picture of these HIV-host interactions, which will illuminate how recognition occurs, and how it might be disrupted to the detriment of the virus. In addition, by comparing structures of proteins bound to multiple partners, or in different states of assembly, we can begin to understand how allosteric changes may modulate host protein function and assembly, and how this is affected by the binding of viral proteins, again with the downstream goal of therapeutic intervention.

The Center is comprised of researchers from nine different laboratories at UCSF and Berkeley, and is one of three Research Centers launched in 2007 by the National Institute of General Medical Sciences (NIGMS) and National Institute of Allergy and Infectious Diseases (NIAID), with the goal of gaining a deeper understanding of the structural biology of HIV. Members of the HARC Center provide expertise within a comprehensive range of biochemical, molecular biological and structural methods, including mass spectroscopy, x-ray crystallography, NMR and cryo-electron microscopy. Two Technology Cores provide services to the projects and innovation of essential methods.

In conjunction with its research activities, the Center makes new methodologies, tools and databases available to the research community at large, and is active in creating new collaborations with outside investigators, including those carrying out associated R21/R33 projects.