- "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. H5N1 binding was similar to H1N1 (human serotype) indicating
a number of H5N1 strains could bind to cells in
- human upper respiratory tract.
- These data are consistent with earlier reports which
indicated H5N1 infected patients had high level of H5N1 in their upper
respiratory tract and levels in the patient's throat were higher than seasonal
- 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 human.
- 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 and prior WHO updates on H5N1 have described
as a lack of "http://www.recombinomics.com/News/06070602/H5N1_Sumatra_Mutationshtml
- significant mutations" in human isolates, imply
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 <http://www.recombinomics.com/News/10220603/H5N1_M230I.html>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 http://www.recombinomics.com/News/12230603/H5N1_Egypt_RBD.html
- additional "human" polymorphisms adjacent to
- receptor binding domain, are cause for concern.