Gharbiya Receptor Binding Domain Change in Togo Poultry
Recombinomics Commentary 12:58
January 31, 2008
The first public sequence from H5N1 in Togo has been released. The HA sequence, A/chicken/Togo/4106-1/2007, includes the receptor binding domain change, V223I. V223I has been seen previously in the Gharbiya cluster at the end of 2006 and was common in recent poultry sequences from Egypt. The recent sequences from Egypt had similarities with the Gharbiya sequences, including V223I and M230I.
The Togo sequence however is distinct from the Egyptian sequences. It has more in common with other west African sequences. The outbreak in Togo last year followed an outbreak in Ghana. A sequence from Ghana was also released, A/chicken/Ghana/2534/2007. That sequence was an exact match with three sequences released by NAMRU-3 last spring, shortly after the Ghana outbreak started. These Ghana sequences are also quite distinct from the Togo sequence.
However, outbreaks in west Africa have been characterized by multiple independent introduction, which would be expected since the west African locations are at the intersection of multiple wild bird flyways. Therefore, the later outbreaks in Ghana may be distinct from the early sequences and may be more closely related to the Tojo sequence.
In any event, the V223I has been appended onto a distinct clade 2.2 genetic background. Prior to the detection of V223I in Egypt, it was present on yet another clade 2.2 genetic background, a whooper swan from Mongolia.
The movement of the same polymorphism from one genetic background to another is common. A dramatic example on NA is G743A, which has now been reported on eleven different clade 2.2 genetic backgrounds, including recently released sequences from Nigeria. G743A was also found in the earlier Ghana sequences, and is likely on the NA sequence from the Ghana sequence above. Only the HA sequences from the above west African isolates was released.
As more sequences are released, more examples of polymorphisms jumping from one genetic background to another are noted.
The recent detection of the Tamiflu resistance marker, H274Y, in human H1N1 is another example. H274Y began to appear in H5N1 in patients treated with Tamiflu, However, it had been seen previously in avian sequences, including a chicken from Hong Kong in 2002 and swans in Astrakhan in 2005. Movement of polymorphisms from one genetic background to another is facilitated by homologous recombination, which occurs during co-infections.
In humans, H274Y began to appear in H1N1 isolates from the United States in early 2007. Now it has exploded in samples collected in late 2007 / early 2008 and is becoming increasing common in Europe and North America. The H1N1 sequences with H274Y are the Solomon Island variant, which traces back to Asia, where Tamiflu blankets were used to control the spread of H5N1.
The sudden appearance of H274Y in the Solomon Island strain of human H1N1 in 2007 / 2008 is not due to de novo mutations and is not an unrelated coincidence.
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