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Shenzhen H5N1 P198S Is In Clade 2.2 Escape Mutant
Recombinomics Commentary 16:30
January 4, 2012

In order to investigate the escape process and to enable predictions of escape, we serially passaged influenza A H5N1 virus in vitro 100 times under immune pressure. The generated escape viruses were characterized phenotypically and in detail by full genome deep sequencing. Mutations already found in natural isolates were detected, evidencing the in vivo relevance of the in vitro induced amino acid substitutions.
The above comments are from an upcoming publication, “Highly Pathogenic Avian Influenza Subtype H5N1 escaping neutralization: more than HA variation” which describe the identification of escape mutants which are present as a minor species in the original sample.  P198S was identified in a swan clade 2.2 (Qinghai strain) isolate from Germany, A/cygnus cygnus/Germany/R65/2006, using this approach, and it was also in a clade 2.2 swan isolate from Russia, A/Cygnus olor/Caspian Sea/2006, confirming it was in circulation in clade 2.2 in Europe in 2006.

P198S was in the recently released sequence from the fatal case in Shenzhen, China, A/Guangdong-Shenzhen/1/2011, which had a large number of HA changes, including the adjacent change Q196K, which is in clade 2.2 isolates in Egypt, Germany, and Kuwait (see list here).

The Shenzhen sequence is clade (Fujian strain) also has another receptor binding domain change, S227R, but was generated via novel coding that was distinct from S227R in clade in Hokkaido and Fukushima.  The coding found in the Shenzhen sequence is found in H5 sequences from wild birds.

H5N1 is frequently found in wild birds in Hong Kong at this time of year, due to migration patterns.  In 2008  clade 2.3.2 was found Japan, South Korea, and Primorsky (southeastern Russia) in poultry and wild birds, which create expansion concerns.  Clade 2.3.2 was subsequently identified in Mongolia, followed by Romania, matching the wild bird path that brought clade 2.2 to Europe, the Middle east, and Africa.

The movement of clade 2.3 into the clade 2.2 flyway created an environment for co-infections and recombination, leading to the acquisition of clade 2.2 polymorphisms in poultry and wild birds in Europe, the Middle East, and Africa.

These interactions lead to rapid evolution as seen in the large number of HA changes in the fatal case in Shenzhen, China.

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