H5N1 Binding to Human Upper Respiratory Cells
Recombinomics Commentary
January 11, 2007
In conclusion, our finding that H5N1 virus infects nasopharyngeal and oropharyngeal epithelia implies that the inefficiency of the avian-to-human or human-to-human transmission of the H5N1 virus may not be explained by the inability of the virus to replicate at these sites. Virus infection of cells that apparently do not express SA2-3Gal1-3GalNAc implies that there may be other binding sites on the epithelium that mediate virus entry. Furthermore, because human H1N1 and avian H5N1 viruses do not differ in their ability to replicate in the alveolar epithelium, we also conclude that the increased severity of human H5N1 influenza cannot be explained purely on the basis of a differential tropism of H5N1 to the lower respiratory tract.
The above comments are from a recent Nature Medicine report on H5N1 binding in ex-vivo tissues from the human upper respiratory tract. H5N1 binding was similar to H1N1 (human serotype), indicating a number of H5N1 strains could bind to cells in the human upper respiratory tract.
These data are consistent with earlier reports which indicated H5N1 infected patients had high levels of H5N1 in their upper respiratory tract, and levels in patient’s throats were higher than seasonal flu.
Similarly, reassortment experiments with ferrets also found high levels of H5N1 in the upper respiratory tract. These data raise serious questions about the emphasis on receptor differences in the upper and lower respiratory tract in humans.
There has been considerable emphasis on possible changes at positions 226 and 228 (H3 numbering). H5N1 and current human H3N2 sequences differ at these positions. Prior WHO updates on H5N1 describe a lack of "significant mutations" in human isolates, implying that positions 226 and 228 had not changed. However, the H5N1 sequence at 226 (Q) and 228(G) is present in early H3N2 human sequences, which were efficiently transmitted from human to human, as well as influenza B, which is currently easily transmitted from human to human.
Moreover, the recent H5N1 Qinghai sequence from a patient in Egypt has M230I, which extends the region of identity with influenza B to positions 226-230 (QSGRI). Moreover, the HA sequences from two of the recent cluster members also have M230I, raising concerns that this polymorphism is becoming fixed in Egyptian Qinghai isolates. M230I is present in all three seasonal flu strains (H1N1, H3N2, influenza B).
Thus, the ability of H5N1 binding to cells in the upper respiratory tract, coupled with the acquisition of additional “human” polymorphisms adjacent to the receptor binding domain, are cause for concern.
Media sources
Phylogenetic Trees