Abstract

P1. Abstract Virus maturation is critical for HIV-1 replication and occurs through an orchestrated series of Gag and Gag-Pol cleavages that result in formation of the conical viral capsid enclosing the viral genomic ribonucleoprotein complex. HIV-1 maturation represents an attractive target for antiviral drug development as evidenced by studies of the small molecule inhibitor bevirimat. In this project, we will employ structural, biochemical, and virological methods to generate new insights into the structure and dynamics of the immature Gag lattice and the effects of maturation inhibitors. We will also define the mechanism by which Integrase-RNA interactions localize the RNP within the viral capsid. Finally, we will dissect the mechanism by which uncleaved matrix-capsid interferes with HIV-1 maturation. These studies will reveal new fundamental aspects of HIV-1 maturation and its inhibition.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM082251-12
Application #
9542836
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
12
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Varlakhanova, Natalia V; Alvarez, Frances J D; Brady, Tyler M et al. (2018) Structures of the fungal dynamin-related protein Vps1 reveal a unique, open helical architecture. J Cell Biol 217:3608-3624
Ning, Jiying; Zhong, Zhou; Fischer, Douglas K et al. (2018) Truncated CPSF6 Forms Higher-Order Complexes That Bind and Disrupt HIV-1 Capsid. J Virol 92:
Himes, Benjamin A; Zhang, Peijun (2018) emClarity: software for high-resolution cryo-electron tomography and subtomogram averaging. Nat Methods 15:955-961
Balasubramaniam, Muthukumar; Zhou, Jing; Addai, Amma et al. (2018) PF74 Inhibits HIV-1 Integration by Altering The Composition of the Preintegration Complex. J Virol :
Lu, Manman; Sarkar, Sucharita; Wang, Mingzhang et al. (2018) 19F Magic Angle Spinning NMR Spectroscopy and Density Functional Theory Calculations of Fluorosubstituted Tryptophans: Integrating Experiment and Theory for Accurate Determination of Chemical Shift Tensors. J Phys Chem B 122:6148-6155
Kraus, Jodi; Gupta, Rupal; Yehl, Jenna et al. (2018) Chemical Shifts of the Carbohydrate Binding Domain of Galectin-3 from Magic Angle Spinning NMR and Hybrid Quantum Mechanics/Molecular Mechanics Calculations. J Phys Chem B 122:2931-2939
Quinn, Caitlin M; Wang, Mingzhang; Polenova, Tatyana (2018) NMR of Macromolecular Assemblies and Machines at 1 GHz and Beyond: New Transformative Opportunities for Molecular Structural Biology. Methods Mol Biol 1688:1-35
Hadden, Jodi A; Perilla, Juan R (2018) All-atom virus simulations. Curr Opin Virol 31:82-91
Yan, Junpeng; Shun, Ming-Chieh; Hao, Caili et al. (2018) HIV-1 Vpr Reprograms CLR4DCAF1 E3 Ubiquitin Ligase to Antagonize Exonuclease 1-Mediated Restriction of HIV-1 Infection. MBio 9:
Dick, Robert A; Zadrozny, Kaneil K; Xu, Chaoyi et al. (2018) Inositol phosphates are assembly co-factors for HIV-1. Nature 560:509-512

Showing the most recent 10 out of 144 publications