For 10 years, the HIV Interactions in Viral Evolution (HIVE) Center characterized at the atomic level the structural and dynamic relationships between interacting macromolecules in the HIV life cycle. HIVE focused on interactions of the major HIV enzymes with their partners and effectors since they encompass key processes in the viral life cycle and as existing drug targets provide a rich base of structural, biological, and evolutionary data that inform our goals. HIVE explored resistance evolution in HIV as an opportune platform upon which to characterize the dynamic relationships between interacting macromolecular structures at the atomic level. This approach is significant due to the promise of new structural insights into the interdependence of viral mechanisms and the direct potential for new drug design methodologies and therapeutic strategies.

The HIVE Center comprised a group of investigators with expertise in HIV crystallography, virology, molecular biology, biochemistry, synthetic chemistry and computational biology, studying the mechanistic implications of viral macromolecular interactions and dynamics and its broader impacts of the evolution of drug resistance to address several biological questions:

• the structural biology of retroviral polyproteins and their components in retroviral assembly and maturation, including study of structural determinants for integrase pleotropism in viral maturation and assembly, and maturation of HIV and PFV polyproteins;
• interactions of HIV with host factors during reverse transcription and integration, including initiation of reverse transcription, inhibition by APOBEC3 family proteins, and the mechanisms of integration into cellular chromatin and their consequences on the formation and reactivation of latent proviruses;

• evolution of antiviral resistance mutations and their biological and biophysical implications, building on computational analysis of full-length genomes obtained from patient samples using an innovative new sequencing technology;
• develop and characterize small molecule probes to understand the biological function of critical molecules and assemblies in the HIV life cycle, including the innovative SuFEx chemistry approach for discovering highly selective covalent inhibitors and computational approaches for discovering new molecules and characterizing the large mesoscale assemblies that are targets of these molecules.