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Mammalian PB2 in Israel H5N1  Increases Pandemic Concerns

Recombinomics Commentary 12:33
April 15, 2008

Full H5N1 sequences from a 2008 isolate from Israel, A/chicken/Israel/1055/2008, have been released.  The HA sequence is closely related to sequences from vaccinated flocks in Egypt.  The Egyptian isolates were collected between mid-December, 2007, and mid-January, 2008, which is the same timeframe as the Israeli isolate.  The HA sequences contained a large number of non synonymous polymorphisms, including M230V.

However, the PB2 sequence also has a number of recent acquisitions, which include mammalian polymorphisms.  One set of three consecutive polymorphisms are found in H1N1 isolates, including the 1918 pandemic strain (see list here).

The acquisition of mammalian polymorphisms is cause for concern.  Earlier (2006) isolates from Egypt and Israel had a series of PB2 mammalian polymorphisms, which were regionally localized.  However, the 2008 isolate has additional acquisitions, including the three linked above.

Like most clade 2.2 isolate, the Israeli isolate also has E627K, a polymorphism found in H1N1 and H3N2 seasonal isolates, including the 1918 pandemic strain. The fixing of E627K has been noted previously as has the associated increase in activity at lower temperatures, which are close to the temperature of a human nose and throat in the winter.

The series of three polymorphisms linked above are clearly acquired via recombination.  Other sequences with that series are distinct from PB2 in clade 2.2 and the Israeli sequence has the Egypt/Israel regional markers that are present in 2006.  Thus, the new acquisitions are appended onto an Egyptian clade 2.2 genetic background.  The likelihood of the acquisitions by selection of random mutations is remote.  However, acquisitions via homologous recombination increase as regions of identity increase due to prior mammalian acquisitions, which are in 2006 isolates.

The presence of a mammalian PB2 in a highly pathogenic H5N1 with a rapidly evolving H5 significantly increases pandemic concerns.

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