1887

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Volume 93, Issue 6

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

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 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.

  • Received:
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© 2012 SGM
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2012-06-01
2024-04-16
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Attenuation of CD4+ T-cell function by human adenovirus type 35 is mediated by the knob protein
J. Gen. Virol. 93, 1339 (2012); https://doi.org/10.1099/vir.0.039222-0
/content/journal/jgv/10.1099/vir.0.039222-0
/content/journal/jgv/10.1099/vir.0.039222-0
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