Avian influenza receptor expression in H5N1-infected and noninfected human tissues

Avian and human influenza viruses preferentially bind to alpha-2,3-linked and alpha-2,6-linked sialic acids, respectively. Until today, the distributions of these two receptor types had never been investigated in H5N1-infected human tissue samples. Here, the expression of avian (AIV-Rs) and human influenza receptors (HuIV-Rs) is studied in various organs (upper and lower respiratory tracts, brain, placenta, liver, kidney, heart, intestines, and spleen) of two H5N1 cases and 14 control cases. Histochemical stains using biotinylated Maackia amurensis lectin 11 and Sambucus nigra agglutinin were performed to localize AIV-Rs and HuIV-Rs, respectively. Immunohistochemical stainings were performed to identify the receptor-bearing cells. AIV-Rs were detected on type II pneumocytes; a limited number of epithelial cells of the upper respiratory tract; and the bronchi, bronchioli, and trachea; as well as on Kupffer cells, glomerular cells, splenic T cells, and neurons in the brain and intestines. HuIV-Rs were abundantly present in the respiratory tract and lungs. They were also detected on Hofbauer cells, glomerular cells, splenic B cells, and in the liver. Moreover, endothelial cells of all organs examined expressed both receptor types. In conclusion, the distribution pattern of AIV-Rs is partially inconsistent with the pattern of infected cells as detected in previous studies, which suggests there may be other receptors or mechanisms involved in H5N1 infection. In addition, the diffuse presence of receptors on endothelial cells may account for the multiple organ involvement in H5N1 influenza. Finally, the relative lack of AIV-Rs in the upper airway may be a one of the factors preventing efficient human-to-human transmission of H5N1 influenza.