HIV-1 Vpu and HIV-2 Env counteract BST-2/tetherin by sequestration in a perinuclear compartment.
BACKGROUND
In the absence of the Vpu protein, newly formed HIV-1 particles can remain attached to the surface of human cells due to the action of an interferon-inducible cellular restriction factor, BST-2/tetherin. Tetherin also restricts the release of other enveloped viral particles and is counteracted by a several viral anti-tetherin factors including the HIV-2 Env, SIV Nef and KSHV K5 proteins.


RESULTS
We observed that a fraction of tetherin is located at the surface of restricting cells, and that co-expression of both HIV-1 Vpu and HIV-2 Env reduced this population. In addition, Vpu, but not the HIV-2 Env, reduced total cellular levels of tetherin. An additional effect observed for both Vpu and the HIV-2 Env was to redirect tetherin to an intracellular perinuclear compartment that overlapped with markers for the TGN (trans-Golgi network). Sequestration of tetherin in this compartment was independent of tetherin's normal endocytosis trafficking pathway.


CONCLUSIONS
Both HIV-1 Vpu and HIV-2 Env redirect tetherin away from the cell surface and sequester the protein in a perinuclear compartment, which likely blocks the action of this cellular restriction factor. Vpu also promotes the degradation of tetherin, suggesting that it uses more than one mechanism to counteract tetherin restriction.
Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
Heiko
H
Hauser
Lisa A
LA
Lopez
Su Jung
SJ
Yang
Jill E
JE
Oldenburg
Colin M
CM
Exline
John C
JC
Guatelli
Paula M
PM
Cannon
D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000737:chemistry; D058851:GPI-Linked Proteins; D019302:HIV Envelope Protein gp160 / Q000378:metabolism*; D015497:HIV-1 / Q000472:pathogenicity*; D015498:HIV-2 / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D025941:Protein Interaction Mapping; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D019302:HIV Envelope Protein gp160; D054298:Human Immunodeficiency Virus Proteins; D008562:Membrane Glycoproteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514798:gp160 protein, Human immunodeficiency virus 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins