It is now well established that the plasma membrane is composed of various types of microdomains containing unique sets of proteins and lipids. Among these, cholesterol- and saturated-lipid-enriched microdomains known as lipid rafts have been the subject of much interest and debate across several disciplines of biology. We and several other groups demonstrated that lipid rafts play important roles in HIV-1 assembly and entry. We have explored the possibility that cholesterol-depleting and cholesterol-binding compounds inhibit HIV-1 replication. Our ongoing studies with amphotericin B methyl ester (AME), a cholesterol-binding polyene fungal antibiotic, have revealed a novel mechanism of escape from an HIV-1 entry inhibitor. The molecular basis for this escape will be defined in future studies. [Corresponds to Freed Project 3 in the April 2007 site visit report of the HIV Drug Resistance Program]

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010777-01
Application #
7592926
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2007
Total Cost
$323,007
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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
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