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H5N1 Iranian Swan Sequence Linked to Italian Swan Sequence  

Recombinomics Commentary

March 14, 2006

The HA 1653 BP sequence of a H5N1 swan isolate from Iran,
A/swan/Iran/754/2006(H5N1), has been made available at GenBank (sequenced in Italy).  As expected, the sequence is over 99% homologous to the Qinghai strain of H5N1 and has an HA cleavage site of GERRRKKR.

However, the isolate has a number of polymorphisms that have a very limited distribution among other Qinghai isolates.  Three of these polymorphisms, T199C, A527G, and T856C are also found in the A/swan/Italy/179/06 isolate, providing tight linkage between the swan sequence in Italy and Iran.  The latter two polymorphisms are also found in a small number of H5N1 isolates from southeast Asia.

Several additional polymorphisms, G530A, G964A, C1213T are not in any Qinghai strain, but are in H5N1 isolates from Southeast or eastern Asia.  Only one polymorphism, T1486C was not represented in the Los Alamos database.

The distribution of the above polymorphisms provide additional evidence from acquisition by recombination.  These polymorphism are over laid on a Qinghai genetic background.  Three have a common link to the Italian swan sequence, but the other polymorphisms are found in Asia.  These are NOT random mutations.  They are found in other H5N1 isolates that are likely candidates for dual infections when the Qinghai strain was circulating in Asia.  These polymorphisms are useful for tracing the movement of the H5N1 isolates.

The polymorphism also point to the large number of regional differences in these sequences.  A large number of swan isolates from Astrakhan have been sequenced and they are also over 99% homologous to the Qinghai strain, yet form two distinct Astrakhan clades which have North American polymorphisms.  Because of the large number of H5N1 outbreaks in countries that have never reported H5N1, the expansion of the H5N1 database should be rapid. Moreover, as noted for the mallard sequence from Italy, differences in species may be more significant.

The data on this isolate from Iran also points to the need for rapid release of data at a public database.  The WHO restricted sequences are analyzed by consultants who do not acknowledge recombination.  They maintain that these changes are due to random mutations and have no predictive value.  However, the data, when properly analyzed shows clear tracings of the movement of the H5N1. 

Moreover, the newly acquired changes can have significant affects on the host range of the H5N1.  In Turkey, as predicted, the isolate from the index case had acquired S227N, which increases the affinity of HA for human receptors.  A similar change G228S is predicted for H5N1 isolates that recombine with H1N1 in European swine.

The analysis of these sequences is most useful when a full and current database is available.  WHO should release the sequestered H5N1 sequences immediately for analysis by the scientific community.

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