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|Paradigm Shift Intervention Monitoring
Homologous Recombination in NP in Korean Chicken
March 5 2005
>> Molecular biologist and flu expert Ron Fouchier of Erasmus University Medical Center in Rotterdam, the Netherlands, says the sequences definitely contain WSN's genetic signature. But he says the fact that the six controversial isolates have varying numbers of WSN fragments points to lab contamination: "If this was an endemic pig virus, I'd expect all viruses to have the same WSN gene segments." <<
There is significant genetic variation in Korea. A recent publication on bird flu in Korea in 2003 found H9N2, H3N2, and H6N1 subtypes. However, within this population there was additional variation. Since most of the sequences were only partial sequences, and none of the NS sequences have been deposited, the public data probably understates the genetic variation due to recombination. However there are clear cut examples in deposited sequences of the H9N2 Korean isolates. The PB2 gene was recombined in A/chicken/Korea/S4/03 with H9N2 genes from Hong Kong. Sequences from two other closely related Korean isolates, S18, and S16 were largely missing the recombined region, so the public information may only contain some of the recombination in these isolates.
Although the 3' half of the S16 PB2 gene was missing from GenBank, the 5' half of NP was present, and it also contained recombination between Korean and Hong Kong avian genes. The recombinant contains sequences that differ from A/guineafowl/Hong Kong/NT184/03 by only 1 bp in the first 234 bp deposited at GenBank. The remaining deposited sequences then matched other 2003 H9N2 Korean isolates. This region in S4 was not deposited at GenBank so it was not possible to determine if a similar recombination had happened in S4.
The available 2003 sequences, however, clearly show two H9N2 Korean isolates recombining with two H9N2 Hong Kong isolates in PB2 and PA.
Thus, finding recombination between WSN/33 and swine H9N2 isolates in Korea would not be unprecedented. There have been no comments suggesting that the sequences of the 2003 Korean avian isolates involved lab contamination or lab errors.
Moreover, additional avian H5N1 isolates from Hong Kong have clear examples of recombination and reassortment with H9N2 or Fujian-like H5N1 in a number of additional genes. Sequences showing recombination in multiple isolates from the same chicken have also been deposited at GenBank by one of the outside labs confirming the swine data.
Thus, the examples of reassortment and recombination have been deposited at GenBank by the major labs generating avian influenza sequences, and the deposited sequences show a great deal of genetic instability in Korea and Hong Kong.