Membrane raft association of the Vpu protein of human immunodeficiency virus type 1 correlates with enhanced virus release.
The Vpu protein of human immunodeficiency virus type 1 (HIV-1) is known to enhance virion release from certain cell types. To accomplish this function, Vpu interacts with the restriction factor known as bone marrow stromal cell antigen 2 (BST-2)/tetherin. In this study, we analyzed whether the Vpu protein is associated with microdomains known as lipid or membrane rafts. Our results indicate that Vpu partially partitions into detergent-resistant membrane (DRM) fractions when expressed alone or in the context of simian-human immunodeficiency virus (SHIV) infection. The ability to be partitioned into rafts was observed with both subtype B and C Vpu proteins. The use of cholesterol lowering lovastatin/M-β-cyclodextrin and co-patching experiments confirmed that Vpu can be detected in cholesterol rich regions of membranes. Finally, we present data showing that raft association-defective transmembrane mutants of Vpu have impaired enhanced virus release function, but still maintain the ability to down-regulate CD4.
Ruiz
Autumn
A
Department of Anatomy and Cell Biology, University of Kansas Medical Center 3901 Rainbow Blvd. Kansas City, Kansas 66160.
Hill
M Sarah
MS
Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center 3901 Rainbow Blvd. Kansas City, Kansas 66160.
Schmitt
Kimberly
K
Department of Anatomy and Cell Biology, University of Kansas Medical Center 3901 Rainbow Blvd. Kansas City, Kansas 66160.
Stephens
Edward B
EB
Department of Anatomy and Cell Biology, University of Kansas Medical Center 3901 Rainbow Blvd. Kansas City, Kansas 66160.|Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center 3901 Rainbow Blvd. Kansas City, Kansas 66160.
D000924:Anticholesteremic Agents / Q000494:pharmacology; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D021962:Membrane Microdomains / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D057074:Virus Release; D000086082:Viroporin Proteins
D000924:Anticholesteremic Agents; D002784:Cholesterol; D054298:Human Immunodeficiency Virus Proteins; D008148:Lovastatin; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins