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H5N1 S227N in Both Turkey Siblings?
April 6, 2006
A leading bird flu expert said on Thursday there was no evidence that the virus was showing any signs of mutating into a form that would be more infectious in humans. But Ian Brown, head of avian influenza at Britain's Veterinary Laboratories Agency, an official lab that tests for the virus, also said that it was extremely difficult to track bird flu as it mutated.
The above comments are curious. Tracking H5N1 bird flu polymorphisms is difficult because most of the sequences from Europe are being withheld by Weybridge's Veterinary Laboratory Agency. The change that has received the most attention has been HA S227N.
Three lines of evidence point toward S227N increased efficiency of H5N1 transmission to humans. The first line comes from receptor binding experiments. H5N1 isolates were screened for increased affinity for human receptors. The 2003 Hong Kong isolates showed increased affinity for human receptors and decreased affinity for avian receptors. Both isolates, A/Hong Kong/212/2003 and A/Hong Kong/213/2003 had been isolated on mammalian MDCK cells and both had S227N.
Recent experiments measuring binding of H5N1 to cells of the upper and lower respiratory tract also showed that the tested Hong Kong isolate could bind to both cell types, also suggesting that such properties would increase transmission to humans. This isolate was also cultured on MDCK cells.
The third line of evidence comes from the size of the familial cluster in Turkey. Although WHO updates withheld disease onset dates and relationships between H5N1 positive patients, media reports indicated that the index case was related to siblings as well as Ozcan cousins. The three sets of cousins accounted for all four fatal H5N1 cases in Turkey as well as three additional confirmed cases.
Media reports indicated that S227N was identified in the index case. A report by the Ministry of Health in China confirmed S227N in A/Turkey/12/2006. However, the isolate from the index case's sister, A/Turkey/15/2006, was also listed in a phylogenetic tree and the sequence was displayed as being identical, indicating that S227N was also in the sister's isolate. Earlier media reports had indicated that the isolate from the sister was negative for S227N, but those same reports suggested that isolation may have involved growth in chicken eggs which selects against receptor binding changes that involve increased affinity for mammalian receptors.
Release of the H5N1 sequences from Turkey would help resolve this issues. Thus far, the only sequence released is from a turkey isolated in October, 2005, A/turkey/Turkey/1/2005. The phylogenetic tree indicates another isolate, A/chicken/Turkey/5/2005, was more closely related to the human isolates. All three sequences are in a private password protected database. These sequences should be released immediately, as H5N1 rapidly spreads and evolves in Europe and worldwide.