Antagonism of CD317 restriction of human immunodeficiency virus type 1 (HIV-1) particle release and depletion of CD317 are separable activities of HIV-1 Vpu.
Vpu antagonizes human immunodeficiency virus type 1 (HIV-1) particle release inhibition by CD317/BST-2/Tetherin. Whether this Vpu activity strictly requires cellular depletion of the restriction factor is unclear. Here, we characterized CD317 variants with mutations in putative sorting or ubiquitination motifs. All mutants still potently impaired release of Vpu-defective HIV-1 and remained sensitive to Vpu-mediated release enhancement. Importantly, this virological antagonism correlated with surface downregulation of CD317 mutants by Vpu, while intracellular pools of these mutants, which were consistently depleted of the wild-type protein, were highly variable or even enhanced. Thus, Vpu can efficiently antagonize virion tethering in the absence of CD317 degradation.
Department of Infectious Diseases, Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany.
Christine
C
Goffinet
Stefanie
S
Homann
Ina
I
Ambiel
Nadine
N
Tibroni
Daniel
D
Rupp
Oliver T
OT
Keppler
Oliver T
OT
Fackler
D015703:Antigens, CD / Q000235:genetics; D058851:GPI-Linked Proteins; D015497:HIV-1 / Q000472:pathogenicity*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D050505:Mutant Proteins; D054334:Viral Regulatory and Accessory Proteins; D037521:Virulence Factors; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins