HIV-1 clade B Tat, but not clade C Tat, increases X4 HIV-1 entry into resting but not activated CD4+ T cells

J Biol Chem. 2010 Jan 15;285(3):1681-91. doi: 10.1074/jbc.M109.049957. Epub 2009 Nov 16.


CXCR4-using human immunodeficiency virus, type 1 (HIV-1) variants emerge late in the course of infection in >40% of individuals infected with clade B HIV-1 but are described less commonly with clade C isolates. Tat is secreted by HIV-1-infected cells where it acts on both uninfected bystander cells and infected cells. In this study, we show that clade B Tat, but not clade C Tat, increases CXCR4 surface expression on resting CD4+ T cells through a CCR2b-dependent mechanism that does not involve de novo protein synthesis. The expression of plectin, a cytolinker protein that plays an important role as a scaffolding platform for proteins involved in cellular signaling including CXCR4 signaling and trafficking, was found to be significantly increased following B Tat but not C Tat treatment. Knockdown of plectin using RNA interference showed that plectin is essential for the B Tat-induced translocation of CXCR4 to the surface of resting CD4+ T cells. The increased surface CXCR4 expression following B Tat treatment led to increased function of CXCR4 including increased chemoattraction toward CXCR4-using-gp120. Moreover, increased CXCR4 surface expression rendered resting CD4+ T cells more permissive to X4 but not R5 HIV-1 infection. However, neither B Tat nor C Tat was able to up-regulate surface expression of CXCR4 on activated CD4+ T cells, and both proteins inhibited the infection of activated CD4+ T cells with X4 but not R5 HIV-1. Thus, B Tat, but not C Tat, has the capacity to render resting, but not activated, CD4+ T cells more susceptible to X4 HIV-1 infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / chemistry
  • Actins / metabolism
  • Antibodies / chemistry
  • Antibodies / immunology
  • Binding Sites
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Chemotaxis
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • HIV-1 / classification
  • HIV-1 / physiology*
  • Humans
  • Lymphocyte Activation*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphorylation
  • Phytohemagglutinins / immunology
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / immunology
  • Receptors, CXCR4 / metabolism
  • Receptors, CXCR5 / metabolism
  • Signal Transduction
  • Species Specificity
  • Up-Regulation
  • Virus Internalization*
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*


  • Actins
  • Antibodies
  • CXCR4 protein, human
  • CXCR5 protein, human
  • HIV Envelope Protein gp120
  • Phytohemagglutinins
  • Receptors, CXCR4
  • Receptors, CXCR5
  • gp120 protein, Human immunodeficiency virus 1
  • tat Gene Products, Human Immunodeficiency Virus
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3