Inhibition of Human Immunodeficiency Virus Type 1 Assembly and Release by the Cholesterol-Binding Compound Amphotericin B Methyl Ester: Evidence for Vpu Dependence

Waheed, Abdül; Ablan, Sherimay D.; Soheilian, Ferri; Nagashima, Kunio; Ono, Akira; Schaffner, Carl P.; Freed, Eric O.

doi:10.1128/jvi.00917-08

Cited by 43 publications

(50 citation statements)

References 35 publications

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“…This is supported by the observation that nystatin affected properties of the arginine and glucose transporters in yeast plasma membrane vesicles (20). Further, the amphotericin B methyl ester inhibited the replication, assembly, and release of HIV-1 by interfering with the ion channel viral protein U (VPU) (18,21). Microarray studies with S. cerevisiae clearly show an increase of expression of transport proteins on treatment with the polyenes amphotericin B and nystatin (22,23).…”

Section: Discussionsupporting

confidence: 54%

Polyene antibiotic that inhibits membrane transport proteins

Welscher

Leeuwen

Kruijff

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The limited therapeutic arsenal and the increase in reports of fungal resistance to multiple antifungal agents have made fungal infections a major therapeutic challenge. The polyene antibiotics are the only group of antifungal antibiotics that directly target the plasma membrane via a specific interaction with the main fungal sterol, ergosterol, often resulting in membrane permeabilization. In contrast to other polyene antibiotics that form pores in the membrane, the mode of action of natamycin has remained obscure but is not related to membrane permeabilization. Here, we demonstrate that natamycin inhibits growth of yeasts and fungi via the immediate inhibition of amino acid and glucose transport across the plasma membrane. This is attributable to ergosterol-specific and reversible inhibition of membrane transport proteins. It is proposed that ergosterol-dependent inhibition of membrane proteins is a general mode of action of all the polyene antibiotics, of which some have been shown additionally to permeabilize the plasma membrane. Our results imply that sterol-protein interactions are fundamentally important for protein function even for those proteins that are not known to reside in sterol-rich domains.

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Section: Discussionsupporting

confidence: 54%

Polyene antibiotic that inhibits membrane transport proteins

Welscher

Leeuwen

Kruijff

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…The intact viral particles within the MVB or "viral exosomes" may be transported subsequently to the cell surface for release. However, viruses seen in these internal structures may also be the result of particles bound by tetherin and internalized (54,82). In most cell types, Gag further moves from the LEs to the plasma membrane to initiate budding.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of Niemann-Pick Type C-1 Protein Impairs Release of Human Immunodeficiency Virus Type 1 and Results in Gag Accumulation in Late Endosomal/Lysosomal Compartments

Tang

Leao

Coleman

et al. 2009

J Virol

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“…One such compound, amphotericin B methyl ester (AME), has been shown to inhibit both virus particle production and virion infectivity (Waheed et al, 2006; Waheed et al, 2008). The infectivity of HIV-1 virions bearing heterologous Env glycoproteins (e.g., from murine leukemia virus or vesicular stomatitis virus) or truncated forms of HIV-1 gp41 is not affected by AME, demonstrating that the long gp41 cytoplasmic tail is required for AME-imposed inhibition of infectivity (Waheed et al, 2006).…”

Section: B Novel Therapeutic Approachesmentioning

confidence: 99%

Novel approaches to inhibiting HIV-1 replication

2010

Self Cite

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Considerable success has been achieved in the treatment of HIV-1 infection, and more than twodozen antiretroviral drugs are available targeting several distinct steps in the viral replication cycle. However, resistance to these compounds emerges readily, even in the context of combination therapy. Drug toxicity, adverse drug-drug interactions, and accompanying poor patient adherence can also lead to treatment failure. These considerations make continued development of novel antiretroviral therapeutics necessary. In this article, we highlight a number of steps in the HIV-1 replication cycle that represent promising targets for drug discovery. These include lipid raft microdomains, the RNase H activity of the viral enzyme reverse transcriptase, uncoating of the viral core, host cell machinery involved in the integration of the viral DNA into host cell chromatin, virus assembly, maturation, and budding, and the functions of several viral accessory proteins. We discuss the relevant molecular and cell biology, and describe progress to date in developing inhibitors against these novel targets.Keywords virus entry; virus assembly; retrovirus; drug resistance; HIV-1 drug therapy A. Introduction A1. Overview of HIV-1 ReplicationThe replication cycle of human immunodeficiency virus type 1 (HIV-1) is a complex multistep process that depends on both viral and host cell factors (Figs. 1 and 2) . Replication begins with viral entry into the target cell. Entry proceeds by fusion of the viral lipid envelope and the cellular plasma membrane (Doms, 2000;Melikyan, 2008). The viral component that mediates fusion is the envelope (Env) glycoprotein spike, which is composed of a trimeric, non-covalently associated complex of the surface glycoprotein gp120 and the transmembrane glycoprotein gp41 (Roux and Taylor, 2007). Fusion is initiated by binding of gp120 to the cellular receptor CD4 and a subsequent interaction with the CCR5 or CXCR4 coreceptor (Berger, Murphy, and Farber, 1999;Doms, 2000). Coreceptor binding triggers a series of conformation changes in both gp120 and gp41 that mediate membrane fusion (Doms, 2000;Melikyan, 2008). Fusion delivers the viral core into the cytoplasm of the target cell. The viral core is composed of a capsid (CA) protein shell that encapsidates the single-stranded, dimeric viral RNA genome in complex with the viral nucleocapsid (NC) protein and the viral Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Adamson and Freed, 2007;GanserPornillos, Yeager, and Sundquist, 2008). The core uncoats (Warrilow and Harrich, 2007) and RT copies the RNA genome into a ...

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Inhibition of Human Immunodeficiency Virus Type 1 Assembly and Release by the Cholesterol-Binding Compound Amphotericin B Methyl Ester: Evidence for Vpu Dependence

Cited by 43 publications

References 35 publications

Polyene antibiotic that inhibits membrane transport proteins

Polyene antibiotic that inhibits membrane transport proteins

Deficiency of Niemann-Pick Type C-1 Protein Impairs Release of Human Immunodeficiency Virus Type 1 and Results in Gag Accumulation in Late Endosomal/Lysosomal Compartments

Novel approaches to inhibiting HIV-1 replication

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