Abstract

This application will examine structural and functional aspects of HIV-1 integration.
The specific aims i nclude: A. Analyzing the integrase active site by site-directed mutagenesis. B. Establishing methods for purifying and concentrating HIV-1 preintegration complexes. C. Examination of higher order protein-protein and protein-DNA interactions important for preintegration complex activity. D. Develop an assay for authentic integration of exogenous HIV-1 DNA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI039394-02
Application #
2429493
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1996-07-01
Project End
2000-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Engelman, Alan N; Singh, Parmit K (2018) Cellular and molecular mechanisms of HIV-1 integration targeting. Cell Mol Life Sci 75:2491-2507
El Ashkar, Sara; Schwaller, Juerg; Pieters, Tim et al. (2018) LEDGF/p75 is dispensable for hematopoiesis but essential for MLL-rearranged leukemogenesis. Blood 131:95-107
Hoyte, Ashley C; Jamin, Augusta V; Koneru, Pratibha C et al. (2017) Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing. J Biol Chem 292:19814-19825
Alvarez, Frances J D; He, Shaoda; Perilla, Juan R et al. (2017) CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction. Sci Adv 3:e1701264
Lesbats, Paul; Engelman, Alan N; Cherepanov, Peter (2016) Retroviral DNA Integration. Chem Rev 116:12730-12757
Serrao, Erik; Cherepanov, Peter; Engelman, Alan N (2016) Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites. J Vis Exp :
Serrao, Erik; Engelman, Alan N (2016) Sites of retroviral DNA integration: From basic research to clinical applications. Crit Rev Biochem Mol Biol 51:26-42
Engelman, Alan; Cherepanov, Peter (2014) Retroviral Integrase Structure and DNA Recombination Mechanism. Microbiol Spectr 2:
Slaughter, Alison; Jurado, Kellie A; Deng, Nanjie et al. (2014) The mechanism of H171T resistance reveals the importance of N?-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Retrovirology 11:100
Wang, Hao; Shun, Ming-Chieh; Li, Xiang et al. (2014) Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Mol Ther Methods Clin Dev 1:

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