Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression

M. Sarah Hill, Autumn Schulze, Kimberly Schmitt, Edward B. Stephens

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)104-112
Number of pages9
JournalVirology
Volume397
Issue number1
DOIs
StatePublished - Feb 5 2010
Externally publishedYes

Fingerprint

HIV-1
Amino Acids
Valine
Amino Acid Substitution
Immunoprecipitation
varespladib methyl
Leucine
Proteins
Mutation

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

Cite this

Identification of amino acids within the second alpha helical domain of the human immunodeficiency virus type 1 Vpu that are critical for preventing CD4 cell surface expression. / Hill, M. Sarah; Schulze, Autumn; Schmitt, Kimberly; Stephens, Edward B.

In: Virology, Vol. 397, No. 1, 05.02.2010, p. 104-112.

Research output: Contribution to journalArticle

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