Receptor Binding Domain Changes in Indonesian H5N1 Cases
Recombinomics Commentary
January 26, 2007
There has been a significant upsurge in cases in Indonesia this month. A large number of suspect cases and clusters have been described in the local media. However, the reports of a jump in suspect cases have been accompanied by a jump in confirmed cases. Four of the five confirmed H5N1 infections this month have been fatal. H5N1 sequences from these cases were made public today at Genbank.
There has been concern about changes in or near the HA receptor binding domain. Recently a number of 2005 and 2006 H5N1 bird sequences in China were made public. These sequences had a number of changes in or near the receptor binding domain.
These changes have recently been appearing in human cases this season. In Egypt, the three sequences from patients in Gharbiya had M230I. This polymorphism is in all three human influenza strains, H3N2, H1N1, influenza B and the change creates a match with Influenza B at positions 226-230. The two isolates from the Gharbiya cluster also have a change within the receptor binding domain, V223I. This change has been found in a Qinghai isolate from Mongolia, as well as recent isolates from geese in Shantou.
Sequences from the four fatal cases in Indonesia, A/Indonesia/CDC1031/2007, A/Indonesia/CDC1032/2007, A/Indonesia/CDC1046/2007, A/Indonesia/CDC1047/2007 also have multiple changes near the receptor binding domain position 190. All four have D187N and A188E. These two changes have been seen in H5N1 birds in Shangxi and Hunan. The changes were also in the more recent 2006 sequences in Indonesia, A/Indonesia/CDC887/2006, A/Indonesia/CDC938/2006. The presence of both changes in all four isolates in 2007 raises the possibility that these changes are being fixed in Indonesia.
Moreover, the three most recent 2007 isolates also have a third change, A189E. The latest acquisitions create a stretch of three consecutive changes at positions 187-189.
The rapid acquisition of changes in or near the receptor binding domain in H5N1 isolates from human cases is cause for concern. All of the above cases have been fatal, and represents a jump in the number of cases in Egypt and Indonesia.
These sequences are being acquired onto regional genetic backgrounds via recombination. The increasingly diverse gene pool, coupled with bird migration and recombination is creating an increasing diversity in key regions such as the receptor binding domain as well as drug resistance to the frontline antiviral, Tamiflu.
These rapid changes in an evolving H5N1 which causes fatal infections in patients, is cause for concern.
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