Abstract
Human immunodeficiency virus type 1 (HIV-1) encodes for a Vpu protein, which interacts with CD4 resulting in its degradation. In this study, we examined the role of the 10 amino acids within the predicted second α-helical domain of the subtype B Vpu cytoplasmic tail in CD4 down-modulation using a VpuEGFP reporter system. Our findings indicate that the invariant leucine at position 63 and, to a lesser extent, the valine at position 68 were required for CD4 down-modulation. Mutation of analogous L63 in Vpu proteins subtypes A2, B(YU-2), C, D, and H also abolished CD4 down-modulation from the cell surface. Co-immunoprecipitation analysis revealed that L63A and V68A mutants were capable of binding CD4 and still retained the ability to interact with h-β-TrCP1. Taken together, these results indicate that amino acid substitutions in the second α-helical domain that retain the predicted structure and binding to h-β-TrCP1 can influence Vpu-mediated CD4 degradation.
Original language | English (US) |
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Pages (from-to) | 104-112 |
Number of pages | 9 |
Journal | Virology |
Volume | 397 |
Issue number | 1 |
DOIs | |
State | Published - Feb 5 2010 |
Keywords
- Alpha helical domain
- CD4 down-modulation
- HIV-1
- Human immunodeficiency virus type 1
- SHIV
- Simian-human immunodeficiency virus
- Vpu
ASJC Scopus subject areas
- Virology