• HIV Interactions in Viral Evolution Center

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

    Slide
  • HIV Interactions in Viral Evolution Center

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

    Slide

About Us

HIVE Center

The HIV Interactions in Viral Evolution (HIVE) Center is characterizing at the atomic level the structural and dynamic relationships between interacting macromolecules in the HIV life cycle. We 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 inform our goals. We 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.

The HIVE Center comprises a group of investigators with expertise in HIV crystallography, virology, molecular biology, biochemistry, synthetic chemistry and computational biology. We 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:

  • 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.

Stefan Sarafianos and Bruce Torbett, Directors

The HIVE Center is directed by Stephan Sarafianos (University of Missouri) and Bruce Torbett (The Scripps Research Institute), and Arthur Olson is coordinator. Together they bring to the HIVE Center decades of experience in the biology of HIV and coordination of collaborative research.

HIVE Team

The HIVE Center characterizes assemblies of HIV and host molecules in multiple states and their transitions, by combining structural studies of HIV protein interactions with chemical and evolutionary probes and computational modeling to elucidate macromolecular interactions and mechanisms critical for the viral life cycle. Previous work by Center structural biologists have characterized all of the HIV enzymes, with over 300 unique structure depositions in the PDB, and the work within HIVE will reveal their interaction and maturation from viral polyproteins, and their interactions within the viral lifecycle. HIVE laboratories are approaching this challenge with a variety of experimental methods. The evolution of HIV under the selection pressure of small molecule effectors provides a functional window on the underlying macromolecular interactions. Chemistry gives us the capability to design and refine new atomic level probes to explore mechanism. Computational modeling guides the establishment of structural hypotheses and enables the integration of multi-scale dynamic data into a coherent physical picture.


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Winter 2017 Meeting