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Journal of Virology, October 2008, p. 9776-9781, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00917-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Abdul A. Waheed,1* Sherimay D. Ablan,1 Ferri Soheilian,2 Kunio Nagashima,2 Akira Ono,1,{dagger} Carl P. Schaffner,3 and Eric O. Freed1

Virus-Cell Interaction Section, HIV Drug Resistance Program,1 Image Analysis Laboratory, Research Technology Program, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, Maryland 21702,2 Department of Microbiology and Biochemistry, The Waksman Institute, Rutgers-The State University of New Jersey, New Brunswick, New Jersey 089033

Received 2 May 2008/ Accepted 11 July 2008

We investigated the mechanism by which the cholesterol-binding compound amphotericin B methyl ester (AME) inhibits human immunodeficiency virus type 1 (HIV-1) particle production. We observed no significant effect of AME on Gag binding to the plasma membrane, Gag association with lipid rafts, or Gag multimerization, indicating that the mechanism of inhibition by AME is distinct from that by cholesterol depletion. Electron microscopy analysis indicated that AME significantly disrupts virion morphology. Interestingly, we found that AME does not inhibit the release of Vpu-defective HIV-1 or Vpu retroviruses such as murine leukemia virus and simian immunodeficiency virus. We demonstrated that the ability of Vpu to counter the activity of CD317/BST-2/tetherin is markedly reduced by AME. These results indicate that AME interferes with the anti-CD317/BST-2/tetherin function of Vpu.


* Corresponding author. Mailing address: Virus-Cell Interaction Section, HIV Drug Resistance Program, NCI-Frederick, Bldg. 535, Rm. 108, Frederick, MD 21702-1201. Phone: (301) 846-1739. Fax: (301) 846-6777. E-mail: awaheed{at}ncifcrf.gov

{triangledown} Published ahead of print on 23 July 2008.

{dagger} Present address: Department of Microbiology and Immunology, University of Michigan Medical School, 6706 Medical Science Building II, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0620.


Journal of Virology, October 2008, p. 9776-9781, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00917-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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