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H5N1 Cleavage Site Reversion in Gharbiya Sequences in Egypt

Recombinomics Commentary 00:55
February 26, 2008

Poultry H5N1 HA sequences from Egypt have been recently released by NAMRU-3.  Included in the released sequences was a series that contained the two receptor binding domain changes present in the Gharbiya cluster, V223I and M230I.  However, this series has a number of additional polymorphisms that had been previously limited to east Asia.  Moreover, many of these changes are non synonymous, raising concerns that the rapid evolution is being driven by mismatched vaccines.  Although the vaccination campaign has been extensive, reports of H5N1 in poultry have been high.

One of the non synonymous changes converts the signature Qinghai polybasic cleavage site of GERRRKKR into the original cleavage site of RERRRKKR, which was first reported in a Guangdong goose in 1996, and subsequently became widespread in eastern Asia in highly pathogenic H5N1.  Although various human clade 2 isolates have signature changes such as RESRRKKR for clade 2.1 in Indonesia and RERRRKR for clade 2.3 (Fujian strain) in China and now moving into southeast Asia, the conversion of the Qingai cleavage site to the original motif has not been reported in public sequences.

However, the largest cluster in Indonesia, the Karo cluster in 2006, has the original cleavage site, which is now on Gharbiya-like sequences in Egypt.  It is not clear if the Tamiflu resistance marker, N294S, is on the avian or human sequences this season, because no NA sequences have been released.

The acquisition of the original consensus cleavage is indicative of multiple changes in the recently released HA sequences.  The recent confirmation of in a child in Minya who has a least one lung infection, in contrast to the mild cases last season, is cause for concern.

Sequences with traditional RERRRKKR cleavage site


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