Inhibition of human immunodeficiency virus type 1 assembly and release by the cholesterol-binding compound amphotericin B methyl ester: evidence for Vpu dependence.
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.
Waheed
Abdul A
AA
Virus-Cell Interaction Section, HIV Drug Resistance Program, NCI-Frederick, Bldg. 535, Rm. 108, Frederick, MD 21702-1201, USA. awaheed@ncifcrf.gov
Ablan
Sherimay D
SD
Soheilian
Ferri
F
Nagashima
Kunio
K
Ono
Akira
A
Schaffner
Carl P
CP
Freed
Eric O
EO
D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D015703:Antigens, CD / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D002784:Cholesterol / Q000378:metabolism*; D058851:GPI-Linked Proteins; D015683:Gene Products, gag / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
D000666:Amphotericin B; D015703:Antigens, CD; D002784:Cholesterol; D058851:GPI-Linked Proteins; D015683:Gene Products, gag; D054298:Human Immunodeficiency Virus Proteins; D008562:Membrane Glycoproteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C017501:methylamphotericin B