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H5N1 Receptor Binding Domain Changes in Shantou China
Recombinomics Commentary
November 7, 2006

H5N1 sequences from patients in Egypt were released today.  The S227N change in the receptor binding domain was reported for one of the eight sequences, bringing the number of human Qinghai sequences with S227N to three.  This change was predicted on October 22, 2005 in a warning issued for an increase in the efficiency of H5N1 transmission in humans.  S227N was subsequently confirmed in the index case for Turkey in January 2006 and was also found in a second isolate from Turkey

To date, only four human sequences from Turkey have been released, so the number of patients positive for S227N remains unknown to the public.  Similarly, only one sequence from the cluster of fatal infections in Azerbaijan has been released.  The three S227N positive patients in Turkey and Egypt suggests additional unreported sequences from the beginning of 2006.  At this time more H5N1 will be migrating into the Middle East, increasing the likelihood of additional acquisitions from H9N2 infected poultry, since H9N2 is endemic to the region.

Sequences released last week also show receptor binding domain changes in H5N1 from a goose in Shantou.  The three changes,  K222R, V223I, and S227R, within such a small region, suggests these changes were also acquired by recombination.  The high level of H5N1 detected in China raise concerns that additional recombination events will further increase the genetic diversity.  The Shantou goose isolate, A/goose/Shantou/2086/2006 also has a novel HA cleavage site, QRERRKKR, again signaling rapid genetic change, which is a characteristic of increased frequencies of recombination among genetically diverse viruses.  Moreover, the Qinghai strain, A/Guinea fowl/Shantou/1431/2006, is also present in Shantou, increasing the likelihood of acquisition of PB2 E627K by recombination or reassortment.

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