Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / genetics
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GPI-Linked Proteins
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HIV-1 / pathogenicity*
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Human Immunodeficiency Virus Proteins / genetics
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Human Immunodeficiency Virus Proteins / physiology*
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Humans
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Membrane Glycoproteins / antagonists & inhibitors*
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Membrane Glycoproteins / genetics
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / genetics
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Mutant Proteins / antagonists & inhibitors
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Mutant Proteins / genetics
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Viral Regulatory and Accessory Proteins / genetics
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Viral Regulatory and Accessory Proteins / physiology*
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Virulence Factors / genetics
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Virulence Factors / physiology*
Substances
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Antigens, CD
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BST2 protein, human
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GPI-Linked Proteins
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Human Immunodeficiency Virus Proteins
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Membrane Glycoproteins
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Membrane Proteins
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Mutant Proteins
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Viral Regulatory and Accessory Proteins
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Virulence Factors
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vpu protein, Human immunodeficiency virus 1