Attenuation of CD4+ T-cell function by human adenovirus type 35 is mediated by the knob protein

J Gen Virol. 2012 Jun;93(Pt 6):1339-1344. doi: 10.1099/vir.0.039222-0. Epub 2012 Feb 22.

Abstract

The complement-regulatory protein CD46 is the primary receptor for human adenovirus type 35 (HAdV-35) and can regulate human immune-cell activation. CD4(+) T-cells are critical for initiating and maintaining adaptive immunity elicited by infection or vaccination. It was reported previously that HAdV-35 can bind these cells and suppress their activation. The data reported here demonstrate that recombinant trimeric HAdV-35 knob proteins alone can induce CD46 receptor downregulation and inhibit interleukin-2 production and proliferation of human CD4(+) T-cells in vitro similarly to mAbs specific to the CD46 region bound by HAdV-35 knobs. A mutant knob protein with increased affinity for CD46 compared with the wild-type knob caused equivalent effects. In contrast, a CD46-binding-deficient mutant knob protein did not inhibit T-cell activation. Thus, the capacity of HAdV-35 to attenuate human CD4(+) T-cell activation depends predominantly on knob interactions with CD46 and can occur independently of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus Infections, Human / genetics
  • Adenovirus Infections, Human / immunology*
  • Adenovirus Infections, Human / virology
  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Cells, Cultured
  • Down-Regulation
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Lymphocyte Activation
  • Membrane Cofactor Protein / genetics
  • Membrane Cofactor Protein / immunology
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology

Substances

  • Capsid Proteins
  • Interleukin-2
  • Membrane Cofactor Protein
  • Receptors, Virus