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H5N1 Swine Evolution Via Recombination in China
Recombinomics Commentary
October 19, 2006

In the past few weeks, the Beijing Genome Institute has released a series of complete H5N1 sequences from poultry, wild birds, and swine in China.  Most of the sequences are from isolates collected between 1997 and 2005 in northeastern China.  Many sequences were initially deposited at GenBank on February 28, 2005 under the title, “A cohort of AIV H5N1 subtypes isolated from wild aquatic birds and domestic poultry revealed rapid transmission, frequent reassortment, and identifiable recombination events.”  Those sequences were made public on February 2, 2006 and had many clear cut examples of recombination.

The current series confirms the earlier sequences and provide a roadmap of recombination events between 1997 and 2005.  These sequences define the evolution of H5N1 in China and highlight the critical role of recombination and migratory birds.  The sequences trace back to low path isolates in Hong Kong in the late 1970’s and show how H5N1 is evolving since the first reported sequence from a 1996 goose in Guangdong.

Of interest are two H5N1 swine sequences from Guangxi and Henan provinces.  These sequence demonstrate the transmission and transport of H5N1 genetic information into the Qinghai strain, which has now been transmitted and transported to most countries in Europe, the Middle East, and Africa.  This strain is recombining with wild birds and poultry in China and swine appear to add additional selection and acquisition of mammalian polymorphisms.

The swine sequences can be found in dog, cat, and wild cat isolates from Thailand, as well as human isolates in Thailand, Vietnam, China, and Indonesia.  The movement of pieces of genes into Indonesian patients, including those on Java as well North Sumatra (the Karo cluster) is striking, and provides additional insight into the evolution and adaptation of H5N1 in mammals.  Some of the swine data is discussed here and here.

The data demonstrates the value in a database of full influenza sequences.  These data add considerably to H5N1 evolution in China and the spread to southeast Asia and Indonesia.  The data also demonstrate movement of sequences to and from North America.

The data clearly show that H5N1 is evolving vioa recombination in a predictable manner that involves migratory birds, dual infections, and exchange of small and large bits of genetic information via recombination.

The database however, still has a large number of holes.  Much of the prior sequences of H5N1 in Hong Kong, China, and southeast Asia are partial sequences, or sequences for one or two of the eight gene segments.  The filling in of those holes would create a more robust database.  The NIAID has a flu sequencing project which will generate full sequences on all eight gene segments at no charge.  The first H5n1 sequences from that project were also released for the first time in the past several weeks.  In addition, full sequences from human isolates in Indonesia have been released ad the number of poultry sequences for one of the eight gene segments has also been increased.  However, sequences collected in Europe beginning in October of 2005 have been withheld as have H5 sequences collected in Canada.  These large sets of withheld data also create large holes in the sequence database.

In addition to withheld data, there are also significant limits on collections.  The data from Indonesia indicate the vast majority of poultry H5N1 isolates do not match the human isolates.  However, there are no swine or wild bird sequences from Indonesia.  There is one cat sequence, which does match the human sequences, and media reports indicate additional cat positives have been found, but none of the sequences have been released.

Similarly, Canada and the United States have now isolated H5 from wild birds in 2005 and 2006, but thus far only 4 of 8 sequences from one H5N2 sample, collected over a year ago in August, 2005 in British Columbia has been released.  It has evidence of recombination and acquisition of North American swine H1N1 sequences and Asian H5N1 Qinghai sequences, demonstrating rapid evolution of low path H5 in North America.  Full sequences of the recent H5N1 isolates in Canada and the United States would provide information on nthe source and rate of this evolution and provide more information on the false negatives recently announced by the USDA.

The predictable evolution of H5N1 is now abundantly clear, and the release of full sequence data is long overdue.

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