Chicken Ig-like receptors represent a multigene family encoded by the leukocyte receptor complex that encode a variety of receptors further subgrouped into activating CHIR-A, inhibitory CHIR-B and bifunctional CHIR-AB. Apart from CHIR-AB that functions as an Fc receptor, CHIR ligands are unknown. In the present study using a panel of different BWZ.36 CHIR reporter cells we identified an interaction between specific CHIR to avian influenza virus (AIV). The specificity of the CHIR-AIV interaction was further demonstrated using CHIR-fusion proteins which bound to AIV coated plates and were able to reduce the interaction of reporter cells with AIV. There was no difference in binding of CHIR to different AIV strains. Furthermore CHIR fusion proteins reduced in vitro AIV induced activation of natural killer (NK) cells obtained from lungs of AIV infected animals as judged by the lower frequency of CD107+ cells. Since the original CHIR reporter lines were generated according to sequence information of the extracellular CHIR domains, we next identified a full length CHIR that displayed similar binding to AIV. The sequence analysis identified this CHIR as a CHIR-A. Neuraminidase treatment of coated CHIR-hIg proteins reduced binding of trimeric H5 proteins to CHIR. This suggests that the interaction is dependent on sialic acid moieties on the receptor. In conclusion, this report identifies AIV as ligand of CHIR-A and describes functional consequences of this interaction.