HIV-1 Vpu's lipid raft association is dispensable for counteraction of the particle release restriction imposed by CD317/Tetherin
- Resource Type
- Authors
- Joëlle V. Fritz; Oliver T. Keppler; Oliver T. Fackler; Nadine Tibroni
- Source
- Virology, 424(1), 33-44. United States (2012).
- Subject
- animal diseases
viruses
Amino Acid Motifs
Human Immunodeficiency Virus Proteins
HIV Infections
Plasma protein binding
Viral Regulatory and Accessory Proteins
Antigens, CD/genetics/metabolism
Peptide sequence
Lipid raft
Virus Release
chemistry.chemical_classification
virus diseases
HIV-1 release
Human Immunodeficiency Virus Proteins/chemistry/genetics/metabolism
Amino acid
Cell biology
HIV-1/genetics/physiology
CRAC motif
lipids (amino acids, peptides, and proteins)
Protein Binding
Immunology & infectious disease [D12] [Human health sciences]
Molecular Sequence Data
Biology
GPI-Linked Proteins
Cell Line
Membrane Lipids
CD317
Antigens, CD
Virology
Vpu
Viral Regulatory and Accessory Proteins/chemistry/genetics/metabolism
HIV Infections/genetics/metabolism/virology
Amino Acid Sequence
Lipid rafts
Cell Membrane
Lipid microdomain
GPI-Linked Proteins/antagonists & inhibitors/genetics/metabolism
biochemical phenomena, metabolism, and nutrition
Immunologie & maladie infectieuse [D12] [Sciences de la santé humaine]
DRM
chemistry
Membrane Lipids/metabolism
Cell culture
HIV-1
Tetherin
Cell Membrane/metabolism/virology
Sequence Alignment
- Language
- ISSN
- 0042-6822
HIV-1 Vpu antagonizes the block to particle release mediated by CD317 (BST-2/HM1.24/Tetherin) via incompletely understood mechanisms. Vpu and CD317 partially reside in cholesterol-rich lipid rafts where HIV-1 budding preferentially occurs. Here we find that lipid raft association of ectopically expressed or endogenous CD317 was unaltered upon co-expression with Vpu or following HIV-1 infection. Similarly, Vpu's lipid raft association remained unchanged upon expression of CD317. We identify amino acids V25 and Y29 of Vpu as crucial for microdomain partitioning and single substitution of these amino acids resulted in Vpu variants with markedly reduced or undetectable lipid raft association. These mutations did not affect Vpu's subcellular distribution and binding capacity to CD317, nor its ability to downmodulate cell surface CD317 and promote HIV-1 release from CD317-positive cells. We conclude that (i) lipid raft incorporation is dispensable for Vpu-mediated CD317 antagonism and (ii) Vpu does not antagonize CD317 by extraction from lipid rafts.