Our Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH) studies the structural biology of HIV-Host interactions involved in viral trafficking and assembly (as broadly defined). Our biological studies will focus on the structural biology, biochemistry, cell biology and molecular virology of five key aspects of the HIV-1 life cycle: 1) Reverse transcription and preintegration complex transformations and trafficking, 2) TRIM5a restriction, 3) Rev-dependent DEAD-box helicase transformations, 4) Virion assembly and budding, and 5) Virion structure, energetics and maturation. In each case, we aim to understand: 1) The molecular machines that drive these events, 2) The mechanisms by which host pathways are recruited and utilized, and 3) The underlying viral and cellular structures. In parallel, we will pursue technological developments in four different areas that will facilitate our biological studies and are important frontiers in HIV research: 1) Single-molecule analyses of native Rev complexes, 2) Multiscale computer simulations of viral capsid structure and assembly, 3) Advances in virus imaging, and 4) Development and application of methodology for imaging HIV in tissues. The efforts of our Center will also be extended through: 1) Extensive collaborations with other PSO Centers and colleagues, and access to scientific resources within the biomedical community, 2) A Collaborative Development Program that will fund promising collaborators who will enhance and benefit from interactions with our Center, and 3) Training programs for younger scientists. Our overall goals are to lay the groundwork for development of new antiviral strategies and to continue to develop HIV into an unparalleled model system for studying how a human virus interacts with its host.

Public Health Relevance

Like other viruses, HIV-1 makes extensive use of host factors and pathways as it traffics through the cell and undergoes the transformations associated with each stage of the viral life cycle. These virus-host interfaces are, in principle, attractive targes for therapeutic intervention. Our program will inform efforts to develop this promise by providing a more comprehensive understanding of the structures, mechanisms, and functions of critical host-virus interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
3P50GM082545-08S1
Application #
8921355
Study Section
Special Emphasis Panel (ZRG1-AARR-K (50))
Program Officer
Sakalian, Michael
Project Start
2007-08-27
Project End
2017-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
8
Fiscal Year
2014
Total Cost
$319,550
Indirect Cost
$74,267
Name
University of Utah
Department
Biochemistry
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Wang, Haoqing; Cohen, Alexander A; Galimidi, Rachel P et al. (2016) Cryo-EM structure of a CD4-bound open HIV-1 envelope trimer reveals structural rearrangements of the gp120 V1V2 loop. Proc Natl Acad Sci U S A 113:E7151-E7158
Monroe, Nicole; Hill, Christopher P (2016) Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines. J Mol Biol 428:1897-911
Imam, Sabrina; Talley, Sarah; Nelson, Rachel S et al. (2016) TRIM5α Degradation via Autophagy Is Not Required for Retroviral Restriction. J Virol 90:3400-10
Grime, John M A; Dama, James F; Ganser-Pornillos, Barbie K et al. (2016) Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly. Nat Commun 7:11568
Chen, Jianbo; Rahman, Sheikh Abdul; Nikolaitchik, Olga A et al. (2016) HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein. Proc Natl Acad Sci U S A 113:E201-8
Chuong, Edward B; Elde, Nels C; Feschotte, Cédric (2016) Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science 351:1083-7
Ma, Hanhui; Tu, Li-Chun; Naseri, Ardalan et al. (2016) Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow. Nat Biotechnol 34:528-30
Iwasa, Janet H (2016) The Scientist as Illustrator. Trends Immunol 37:247-50
Li, Yen-Li; Chandrasekaran, Viswanathan; Carter, Stephen D et al. (2016) Primate TRIM5 proteins form hexagonal nets on HIV-1 capsids. Elife 5:
Coey, Aaron; Larsen, Kevin; Puglisi, Joseph D et al. (2016) Heterogeneous structures formed by conserved RNA sequences within the HIV reverse transcription initiation site. RNA 22:1689-1698

Showing the most recent 10 out of 130 publications