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HIV Interaction and Viral Evolution Center

Characterizing at the atomic level the structural and dynamic relationships between interacting macromolecules in the HIV life cycle.

 

Understanding the structural interactions of HIV assembly, maturation and replication is critical to linking the current structural knowledge of two of the major enzymatic targets, HIV protease and reverse transcriptase, with their polyprotein precursors, substrates and effectors. Expanding the evolving structural knowledge of the HIV integrase and its interactions with host proteins will provide a more complete picture of the mechanisms of the third major drug target. We have formed the HIV Interaction and Viral Evolution (HIVE) Center to characterize at the atomic level the structural and dynamic relationships between interacting macromolecules in the HIV life cycle. We will focus 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 will serve to inform our goals. We will explore resistance evolution in HIV as an opportune platform upon which to characterize the dynamic relationships between interacting macromolecular structures at the atomic level. Our 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.

HIVE summary figure

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

  • How do structures of the HIV polyprotein precursors direct assembly, maturation, and replication?
  • What novel HIV–Host interactions drive DNA replication and integration?
  • How does dynamics impact viral function and fitness and how can it be exploited for therapeutic targeting?
  • What are the structural and dynamic consequences of resistance mutations in the HIV life cycle?

 


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