Principal investigator: Alice Telesnitsky, Ph.D., University of Michigan

This center studies the structural biology of viral RNA and its interactions with viral and host proteins. Because RNA is less amenable to structural analysis than proteins are, the researchers are developing approaches to overcome this technical challenge. Their work could help identify RNA-based targets for HIV treatments as well as shed light on the multiple biological functions of the viral genome.

Principal investigator: Nevan Krogan, Ph.D., University of California, San Francisco

The HARC Center mission is to elucidate the molecular basis of systems that are essential for, or contribute to, the pathogenesis of HIV/AIDS, including the physical/functional interactions that occur between viral accessory and regulatory proteins and human proteins, membranes, lipids and nucleic acids (DNA/RNA). Through a powerful structure/function pipeline, including genetic approaches, the HARC team is gaining unprecedented insight into HIV biology, new avenues to complex structures, and the potential to fundamentally alter treatment strategies by targeting key cellular processes that contribute to AIDS at interfaces where mutational resistance is highly unlikely. The Center is also developing new technologies to drive forward work in the center and the field in general, including high resolution cryo-EM approaches, a pipeline for recombinant antibody reagents, novel proximity-based and post-translational mass spectrometry approaches and a CRISPR-cas9 based approach for functional study of host genes in T cells.

Principal investigator: Angela Gronenborn, Ph.D., University of Pittsburgh School of Medicine

The PCHPI is focused on structure determination and imaging of pivotal events that occur during viral particle maturation, post-entry events, nuclear entry and integration. The center applies proteomic approaches to identify novel HIV-interacting host proteins and integrates virological and biochemical approaches in the interrogation of these interactions with structural methodologies for understanding the viral-host interplay. Structural methodologies encompass solution and solid-state NMR spectroscopy, X-ray crystallography, cryo-electron microscopy, and MD simulations, with an emphasis on further developing novel approaches that advance the capabilities of these techniques.

Principal investigators: Bruce Torbett, Ph.D., The Scripps Research Institute and Stephanos Sarafianos, Ph.D., Emory University

The Behavior of HIV In Viral Environments (B-HIVE) Center furthers the understanding of HIV-1 and its interactions with cellular host factors within distinct cellular environments that shape the HIV replication cycle. With the limited size of the HIV RNA genome, it is no surprise that many of the same gene products end up performing different functions in different cellular environments at different times during replication. These various HIV-1-cell host factor interactions promote the cellular pathogenesis, and ultimately disease, characteristic of HIV-1/AIDS. Building on ten successful years of research from the HIVE Center, B-HIVE members collaboratively explore three complementary Projects that focus on specific stages of the viral replication cycle. More information available on their website.

The new DHVI center will focus on three pursuits:

1. Detailing the multiple steps that occur when HIV enters the body, with special emphasis on identifying several short-lived stages that have proven elusive and appear integral to the process. This project is led by Rory Henderson, Ph.D., assistant professor in the Department of Medicine at Duke.

2. Building a model of how the surface of a B cell, an important immune responder, displays the receptor that interacts with antigens on viral and bacterial pathogens. This will help researchers better understand how pathogen-derived antigens interact and activate the immune system to generate antibodies. The project lead is S. Munir Alam, Ph.D., professor in the departments of Medicine and Pathology at Duke.

3. Determining how the autologous neutralizing antibody response to the HIV Envelope protein can be used to block viral rebound and achieve a functional cure. Janet Siliciano, Ph.D., at Johns Hopkins University School of Medicine is leading this project.