title: Anti-tetherin activities of HIV-1 Vpu and Ebola virus glycoprotein do not involve removal of tetherin from lipid rafts.
abstract: BST-2/tetherin is an interferon-inducible host restriction factor that blocks the release of newly formed enveloped viruses. It is enriched in lipid raft membrane microdomains, which are also the sites of assembly of several enveloped viruses. Viral anti-tetherin factors, such as the HIV-1 Vpu protein, typically act by removing tetherin from the cell surface. In contrast, the Ebola virus glycoprotein (GP) is unusual in that it blocks tetherin restriction without apparently altering its cell surface localization. We explored the possibility that GP acts to exclude tetherin from the specific sites of virus assembly without overtly removing it from the cell surface and that lipid raft exclusion is the mechanism involved. However, we found that neither GP nor Vpu had any effect on tetherin's distribution within lipid raft domains. Furthermore, GP did not prevent the colocalization of tetherin and budding viral particles. Contrary to previous reports, we also found no evidence that GP is itself a raft protein. Together, our data indicate that the exclusion of tetherin from lipid rafts is not the mechanism used by either HIV-1 Vpu or Ebola virus GP to counteract tetherin restriction.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lopez
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Yang
authors.forename: Colin M
authors.initials: CM
authors.lastname: Exline
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rengarajan
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Haworth
authors.forename: Paula M
authors.initials: PM
authors.lastname: Cannon
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D029043:Ebolavirus / Q000235:genetics / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D019142:Hemorrhagic Fever, Ebola / Q000378:metabolism* / Q000821:virology; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D008051:Lipid Bilayers; D014759:Viral Envelope Proteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C113189:envelope glycoprotein, Ebola virus; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins