Abstract

This application proposes to study the process of HIV integration by (1) purifying preintegrative complexes to near homogeneity and determine the protein composition and stoichiometry, (2) characterizing the structure of isolated preintegrative complexes in detail using electron microscopy and assays for protein-DNA interactions, and (3) to build upon the exciting finding that HMG I(Y) is a likely component of the preintegrative complex by examining its role in the integration process in vivo and in vitro.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI034786-06
Application #
2672254
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1993-07-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Ciuffi, Angela; Diamond, Tracy L; Hwang, Young et al. (2006) Modulating target site selection during human immunodeficiency virus DNA integration in vitro with an engineered tethering factor. Hum Gene Ther 17:960-7
Ciuffi, Angela; Bushman, Frederic D (2006) Retroviral DNA integration: HIV and the role of LEDGF/p75. Trends Genet 22:388-95
Lewinski, Mary K; Yamashita, Masahiro; Emerman, Michael et al. (2006) Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog 2:e60
Wang, Gary P; Bushman, Frederic D (2006) A statistical method for comparing viral growth curves. J Virol Methods 135:118-23
Diamond, Tracy L; Bushman, Frederic D (2005) Division of labor within human immunodeficiency virus integrase complexes: determinants of catalysis and target DNA capture. J Virol 79:15376-87
Barr, Stephen D; Leipzig, Jeremy; Shinn, Paul et al. (2005) Integration targeting by avian sarcoma-leukosis virus and human immunodeficiency virus in the chicken genome. J Virol 79:12035-44
Lewinski, M K; Bisgrove, D; Shinn, P et al. (2005) Genome-wide analysis of chromosomal features repressing human immunodeficiency virus transcription. J Virol 79:6610-9
Groschel, Bettina; Bushman, Frederic (2005) Cell cycle arrest in G2/M promotes early steps of infection by human immunodeficiency virus. J Virol 79:5695-704
Ciuffi, Angela; Llano, Manuel; Poeschla, Eric et al. (2005) A role for LEDGF/p75 in targeting HIV DNA integration. Nat Med 11:1287-9
Gao, Kui; Wong, Steven; Bushman, Frederic (2004) Metal binding by the D,DX35E motif of human immunodeficiency virus type 1 integrase: selective rescue of Cys substitutions by Mn2+ in vitro. J Virol 78:6715-22

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