H5N1 Mammalian Receptor Binding in Indonesia
Recombinomics Commentary
June 9, 2006
I began research in February-March 2006. This research was sponsored by Tokyo University.
The samples that I tested came from poultry, swine and humans. Of the 100 samples, there were 20 that succeeded in being brought to life and actually 11 of them had the receptor specificity 2.6.
a portion of those samples had the amino acid lysine at number 627 protein PB2, which means that the virus can be stable at the human body temperature.
The above human translation of an interview of Dr CA Nidom from the Avian Influenza Laboratory Tropical Disease Center and the Department of Biochemistry and Molecular Biology from the Faculty of Veterinary Medicine at Airlangga University, Surabaya. Dr Nidom has previously identified H5N1 in swine in Indonesia, including Tangerang, not far from the residence of the first reported H5N1 cluster in Indonesia.
The current interview raises a number of important questions that are not easily answered with the information above. Additional information indicates that 3 of the 11 isolates with alpha 2,6 specificity also had PB2 E627K. Since alpha 2,6 linkages are found in mammalian upper respiratory tract, it is likely that those 11 isolates with 2,6 specificity were from swine or humans. The only H5N1 from birds that have E627K are in the Qinghai strain. However, all of the human H5N1 isolates described to date are readily distinguished from the Qinghai strain. This can be seen in the phylogenetic tree generated by China's Ministry of Health. It contains data for the first two H5n1 isolated form humans in Indonesia. The first isolate was Indonesia/5/2005, which was from the father in the Tangerang cluster. The second isolate, Indonesia/6/2005, was from a patient who lived in southwest Jakarta and is thought to have been infected by home fertilizer. These two isolates are at opposite sides of the Indonesia branch, which is distinct from the Qinghai isolates, which are from Qinghai and Turkey in the isolates represented on the tree.
All of the other human isolates from Indonesia are similar to the first Indonesian isolate. They have a novel cleavage site, RESRRRKKR, as does a H5N1 from a cat in Jakarta. The samples described by CA Nidom also are from the Jakarta area and the cleavage site does not match the poultry isolates from the region. However, these two named isolates above have been described in WHO updates and there was no mention of the 2.6 receptor specificity.
This difference could be explained by isolation procedures. Isolating human H5N1 in chicken eggs will select against H5N1 with alpha 2,6 specificity. Since the 2.6 linkage is found in the upper respiratory tract of humans, H5N1 with that specificity would be more efficiently transmitted from human-to-human. Indonesia has reported a large number of familial clusters, and most have a gap between disease onset dates of the index case and other family members, strongly suggested that most or all are from human-to-human transmission.
Thus, more detail on the distribution of alpha 2,6 specificity among human and swine isolates, as well as sequence data from these isolates, would be useful.
Media Source Link
Phylogenetic Tree