Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B cells

Nat Immunol. 2006 Mar;7(3):302-10. doi: 10.1038/ni1302. Epub 2006 Jan 22.


Immunoglobulin class switching from immunoglobulin M (IgM) to IgG and IgA is central to immunity against viruses and requires the activation of B cells by T cells via CD154 (CD40 ligand) and cytokines. These molecules limit their signaling activity in immune cells by turning on negative feedback proteins, including IkappaB and SOCS. We show here that negative factor (Nef) protein, an immunosuppressive human immunodeficiency virus 1 protein expressed and released by infected cells, penetrates B cells both in vivo and in vitro. Nef suppressed immunoglobulin class-switch DNA recombination by inducing IkappaBalpha and SOCS proteins, which blocked CD154 and cytokine signaling via NF-kappaB and STAT transcription factors. Thus, human immunodeficiency virus 1 may evade protective T cell-dependent IgG and IgA responses by 'hijacking' physiological feedback inhibitors in B cells via Nef.

Publication types

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

MeSH terms

  • B-Lymphocytes / immunology*
  • B-Lymphocytes / virology
  • Bystander Effect / immunology*
  • CD40 Antigens / immunology*
  • CD40 Antigens / metabolism
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Products, nef / immunology*
  • Gene Products, nef / metabolism
  • HIV-1 / immunology*
  • Humans
  • I-kappa B Kinase / immunology
  • I-kappa B Kinase / metabolism
  • Immunoblotting
  • Immunoglobulin Class Switching / immunology*
  • Immunohistochemistry
  • Microscopy, Confocal
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT Transcription Factors / immunology
  • STAT Transcription Factors / metabolism
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • nef Gene Products, Human Immunodeficiency Virus


  • CD40 Antigens
  • Gene Products, nef
  • NF-kappa B
  • STAT Transcription Factors
  • Suppressor of Cytokine Signaling Proteins
  • nef Gene Products, Human Immunodeficiency Virus
  • CD40 Ligand
  • I-kappa B Kinase