Influenza virus tropisms.

Human and avian influenza viruses target different cell types in human airway epithelium. Recent outbreaks of avian influenza infections in humans highlighted the threat of pathogenic influenza viruses emerging from a huge natural reservoir in birds. To initiate the infection, avian influenza viruses bind to cell-surface receptors containing terminal sialyl-galactosyl residues linked by 2-3-linkage, whereas human viruses, including the earliest available pandemic isolates, bind to receptors that contain terminal 2-6-1inked sialyl-galactosyl residues. It is believed that a nonoptimal receptor specificity of avian viruses limits their replication in human respiratory tract and pandemic spread, but the mechanism of this restriction is not clear. Ciliated epithelium of conducting airways consists of several distinct cell types with different functions, but the roles of specific cell types in virus replication have not been defined. To investigate cellular tropism of influenza viruses, the authors employed cultures of differentiated human airway epithelial cells which closely mimic airway epithelium in vivo. The authors found that human viruses preferentially infected nonciliated cells, whereas avian viruses mainly infected ciliated cells; this pattern correlated with cell type-specific distribution of sialic acid receptors recognized by the viruses. This study suggests that two widely held concepts concerning influenza viruses (uniform susceptibility of airway epithelial cells to human viruses and a lack of receptors for avian viruses) are incorrect. These data provide insight on the emergence of pandemic viruses and open avenues for cellular studies on influenza virus replication and pathogenicity in humans.

Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD. Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proc Natl Acad Sci U S A. 2004;101:4620-4. Epub 2004 Mar 15.