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Updated: May 24, 2026

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
15:33

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation

Published on: August 13, 2013

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

William C Adams1, Ronald J Berenson2, Gunilla B Karlsson Hedestam3

  • 1Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

The Journal of General Virology
|February 24, 2012
PubMed

Insights

Human adenovirus type 35 (HAdV-35) knob proteins alone suppress CD4(+) T-cell activation by downregulating CD46 receptors. This interaction inhibits T-cell proliferation and interleukin-2 production, independent of viral infection.

Area of Science:

  • Immunology
  • Virology

Background:

  • CD46 is a complement-regulatory protein and the primary receptor for human adenovirus type 35 (HAdV-35).
  • CD4(+) T-cells are crucial for adaptive immunity, and HAdV-35 has been previously shown to bind and suppress their activation.

Purpose of the Study:

  • To investigate the mechanism by which HAdV-35 knob proteins interact with CD46 to inhibit CD4(+) T-cell activation.
  • To determine if HAdV-35 knob-mediated T-cell suppression is dependent on viral infection.

Main Methods:

  • Utilized recombinant trimeric HAdV-35 knob proteins (wild-type and mutants with altered CD46 affinity).
  • Assessed CD46 receptor downregulation, interleukin-2 production, and proliferation of human CD4(+) T-cells in vitro.
  • Compared effects of knob proteins with monoclonal antibodies (mAbs) specific to the CD46 binding region.

Main Results:

  • Recombinant HAdV-35 knob proteins alone induced CD46 receptor downregulation on CD4(+) T-cells.
  • Knob proteins inhibited interleukin-2 production and proliferation of CD4(+) T-cells in vitro.
  • A knob mutant with deficient CD46 binding did not inhibit T-cell activation, while a high-affinity mutant showed equivalent inhibition to wild-type.

Conclusions:

  • HAdV-35 knob protein interaction with CD46 is the predominant mechanism for attenuating human CD4(+) T-cell activation.
  • This immunosuppressive effect can occur independently of HAdV-35 infection, highlighting a direct role for the viral knob protein.

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