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

W. C. Adams, R. J. Berenson, G. B. Karlsson Hedestam, A. Lieber, R. A. Koup, K. Lore
2012 Journal of General Virology  
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
more » ... rleukin-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. 3Present address:
doi:10.1099/vir.0.039222-0 pmid:22357750 fatcat:wsmltmex6fhf5kwba33gvfthhm