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H5N1 in Shantou China Lacks Regional Qinghai Sequences
December 7, 2006
A large series of H5N1 sequences from 2005 and 2006 isolates in southern China has been released. There isolates were described in a recent PNAS paper on the spread of Fujian H5N1 in China. The paper included 404 HA sequences as well as 156 PB2 sequences, but no sequence data from the other six gene segments. The current set of sequences (see list here) are from the previously described isolates, but have a large number of sequences for each of the six gene segments that were described in the earlier publication.
Included were the additional sequences for A/Guinea fowl/Shantou/1341/2006, which was the only Qinghai isolate in the series. Initially the HA and PB2 sequences were released, which contained the common Qinghai HA cleavage site, as well as the mammalian polymorphism, PB2 E627K. Both genes were also mostly closely related to other Qinghai isolates. However, the isolate was readily distinguished from the other Qinghai isolates, because the polymorphisms with limited distribution with the Qinghai group, were usually found in H5N1 that were not Qinghai.
Analysis of the six additional gene segments extends these observation. All six gene segments are most closely related to Qinghai isolates, but the polymorphisms with limited distribution are generally shared with H5N1 isolates from Asia (China, Vietnam, Thailand, and Indonesia).
MP and NP do not have Qinghai polymorphisms among the seven polymorphisms with limited distribution. Similarly, only one of the eight PA polymorphisms is shared with a single Qinghai isolate from Astrakhan. The same is true fro the six PB1 polymorphisms (found in a single Qinghai isolate in Egypt). NA and NS each have one of two polymorphism found in a broader subset of Qinghai isolates, but the vast majority of polymorphisms are not in any Qinghai isolates on the public side of sequences at the Los Alamos flu database.
These data provide evidence for the acquisition of new polymorphism via recombination between co-circulating influenza isolates. For Qinghai strains, the new acquisitions are frequently from other distinct Qinghai isolates, leading to an expansion of regional polymorphism.
For the Shantou isolate, other Qinghai isolates from eastern Asia are not present in the public databases at Los Alamos or Genbank. Consequently, shared polymorphisms are readily found, but they are not in public Qinghai sequences.
The absence of such isolates highlight surveillance shortfalls in the region. The vast majority of the H5N1 sequences from southern China were from live markets, which appear to significantly under-represent Qinghai sequences. Consequently, only one sequence has been isolated in Asia, while virtually all H5N1 sequences west of China are the Qinghai nstrain, including over 700 PCR positive samples in Europe in late 2005 and 2006, the same time frame represented by the southern China isolates.
The analysis of these polymorphisms demonstrates the ability to distinguish the Qinghai strain as well as monitor the movement of these polymorphisms acquired via recombination. These data support the conclusion that these single nucleotide polymorphisms are not random or due to recent mutations, but instead are changes acquired through recombination with co-circulating strains of influenza.