Abstract

The release of retrovirus particles from the infected cell is greatly stimulated by """"""""late"""""""" domains present within the Gag precursor protein. Three distinct retroviral late-domain sequences have been identified: Pro-Thr/Ser-Ala-Pro (PTAP), Pro-Pro-x-Tyr (PPxY), and Tyr-Pro-x-Leu (YPxL). We played a key early role in identifying the PTAP late domain of HIV-1, and recent studies from our lab and others have demonstrated that late domains function by interacting with components of the multivesicular body (MVB) sorting machinery. We continue to be actively involved in elucidating the host cell machinery involved in the release of HIV-1 and other lentiviruses (e.g., EIAV and FIV) and have initiated studies aimed at identifying inhibitors of retrovirus budding. [Corresponds to Freed Project 2 in the April 2007 site visit report of the HIV Drug Resistance Program]

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010776-02
Application #
7733214
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2008
Total Cost
$430,837
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Waheed, Abdul A; Ono, Akira; Freed, Eric O (2009) Methods for the study of HIV-1 assembly. Methods Mol Biol 485:163-84
Adamson, Catherine S; Freed, Eric O (2009) Anti-HIV-1 therapeutics: from FDA-approved drugs to hypothetical future targets. Mol Interv 9:70-4
Viard, Mathias; Ablan, Sherimay D; Zhou, Ming et al. (2008) Photoinduced reactivity of the HIV-1 envelope glycoprotein with a membrane-embedded probe reveals insertion of portions of the HIV-1 Gp41 cytoplasmic tail into the viral membrane. Biochemistry 47:1977-83
Liu, Fa; Stephen, Andrew G; Waheed, Abdul A et al. (2008) SAR by oxime-containing peptide libraries: application to Tsg101 ligand optimization. Chembiochem 9:2000-4
Joshi, Anjali; Munshi, Utpal; Ablan, Sherimay D et al. (2008) Functional replacement of a retroviral late domain by ubiquitin fusion. Traffic 9:1972-83
Saad, Jamil S; Ablan, Sherimay D; Ghanam, Ruba H et al. (2008) Structure of the myristylated human immunodeficiency virus type 2 matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in membrane targeting. J Mol Biol 382:434-47
Ono, Akira; Waheed, Abdul A; Freed, Eric O (2007) Depletion of cellular cholesterol inhibits membrane binding and higher-order multimerization of human immunodeficiency virus type 1 Gag. Virology 360:27-35
Garg, Himanshu; Joshi, Anjali; Freed, Eric O et al. (2007) Site-specific mutations in HIV-1 gp41 reveal a correlation between HIV-1-mediated bystander apoptosis and fusion/hemifusion. J Biol Chem 282:16899-906
Adamson, Catherine S; Freed, Eric O (2007) Human immunodeficiency virus type 1 assembly, release, and maturation. Adv Pharmacol 55:347-87