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 others 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 efforts have focused on amphotericin B methyl ester (AME), a cholesterol-binding polyene fungal antibiotic. We have observed that AME inhibits both assembly/release and virus entry and have identified a novel mechanism of escape from this compound, involving cleavage of the cytoplasmic tail of gp41 by the viral protease (PR). [Corresponds to Freed Project 3 in the April 2007 site visit report of the HIV Drug Resistance Program]

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Adamson, Catherine S; Freed, Eric O (2010) Novel approaches to inhibiting HIV-1 replication. Antiviral Res 85:119-41
Waheed, Abdul A; Freed, Eric O (2010) The Role of Lipids in Retrovirus Replication. Viruses 2:1146-1180
Waheed, Abdul A; Ablan, Sherimay D; Sowder, Raymond C et al. (2010) Effect of mutations in the human immunodeficiency virus type 1 protease on cleavage of the gp41 cytoplasmic tail. J Virol 84:3121-6
Waheed, Abdul A; Ono, Akira; Freed, Eric O (2009) Methods for the study of HIV-1 assembly. Methods Mol Biol 485:163-84
Waheed, Abdul A; Freed, Eric O (2009) Lipids and membrane microdomains in HIV-1 replication. Virus Res 143:162-76
Adamson, Catherine S; Freed, Eric O (2009) Anti-HIV-1 therapeutics: from FDA-approved drugs to hypothetical future targets. Mol Interv 9:70-4
Greene, Warner C; Debyser, Zeger; Ikeda, Yasuhiro et al. (2008) Novel targets for HIV therapy. Antiviral Res :
Adamson, Catherine S; Freed, Eric O (2008) Recent progress in antiretrovirals--lessons from resistance. Drug Discov Today 13:424-32
Joshi, Anjali; Garg, Himanshu; Nagashima, Kunio et al. (2008) GGA and Arf proteins modulate retrovirus assembly and release. Mol Cell 30:227-38