Abstract – Overall Approximately 40 million people worldwide are living with HIV/AIDS; however, a protective vaccine or functional cure remain elusive despite four decades of intense research. HIV-1 evades the immune system through its rapid structural evolution during infection and replication. The proposed Duke Center for HIV Structural Biology will provide new insights into the dynamics of HIV-1 entry and fusion with the host membrane, the Env-initiated immune activation of B-cell receptors, and the role of anti-Env antibodies in blocking viral rebound. The Center will pursue structural studies that aim to 1) to develop a complete, time resolved and atomically detailed mechanism of HIV-1 Env fusion; 2) to define BCR complex structures with specificity of autologous (anAb) and broadly neutralizing antibodies (bnAb); and 3) to achieve an atomic level understanding of antibody-mediated control of rebound from latent HIV-1 reservoirs. The ultimate goal of these studies is to advance structural biology techniques and knowledge of HIV-1 Env structure-derived disease mechanisms in HIV-1 infection and rebound. Additionally, through its Developmental Core, the Center will provide resources and training opportunities for early career investigators and trainees who are pursuing careers in the field of HIV-1 structural biology.

Narrative Approximately 40 million people worldwide are living with HIV/AIDS; however, a protective vaccine or functional cure remain elusive despite four decades of intense research. The proposed Duke Center for HIV Structural Biology will provide new insights into the dynamics of HIV-1 entry and fusion with the host membrane, the Env-initiated immune activation of B-cell receptors, and the role of anti-Env antibodies in blocking viral rebound. The ultimate goal of these studies is to advance structural biology techniques and knowledge of HIV-1 Env structure-derived disease mechanisms in HIV-1 infection and rebound.