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Novel Bird Flu Genes in Grey Herons in Hong Kong

Recombinomics Commentary
January 20, 2005

>> Both isolates were confirmed as highly pathogenic H5N1 viruses by PCR(1) and sequencing results. Phylogenetic analysis showed both viruses were closely related in all eight gene segments.
However, they were novel reassortants with HA and NA genes similar to a H5N1 virus isolated from geese in December 2002 but four internal genes from a novel source. These viruses are not the same as H5N1 viruses that infected family members in Fujian in 2003, nor the viruses causing human fatalities in Thailand and Vietnam, or HPAI outbreaks in poultry in the East and South-East Asian regions in 2004<<.

The comments above indicate new bird flu genes were detected in Hong Kong grey herons last month and the data highlights additional instability in H5N1 in Asia.  The geese from December, 2002 would be represented by A/Gs/HK/739.2/02 which was isolated from a Canada goose (Branta canadensis), found in Penfold Park on Dec 4, 2002 in Hong Kong.  The H5 was closely related to A/G.H./HK/793.1/02 which was isolated from a dead grey heron (Ardea cinerea), found on Dec 17, 2000 in Lok Ma Chau,  as well as another grey heron from Hong Kong in 2002, A/grey heron/HK/861.1/2002(H5N1).  However, the N1 from the goose did not have the 20 aa deletion found in the 2002 grey herons, as well as the H5N1 isolates from Vietnam and Thailand in 2004.

The H5N1 isolated from two grey herons last month in Hong Kong preview the new sequences for this season.  Thus, they had an H and N like the Canada goose, which was distinct from the 2002 grey herons in Hong Kong, and they also had 4 novel internal genes.  Frequently, "novel genes" in H5N1 are really recombinant genes, but the reassortment demonstrates the continued instability in H5N1 in Asia and suggests this season will involve new genes and new problems.

Although recombination creates new genes, the reassortment puts reshuffled genes into novel environments, which can lead to dramatic genetic change, the hallmark of a flu pandemic.  The swine in Korea are a good example.  The six isolates have various combinations of human genes from 1933 (WSN/33) and Korean avian genes from 2003.  The number of human genes in the reassorted isolates is 7,5,4, or 3.  The two isolates with 7 human genes are H1N1.  Only PB2 is avian.  The other 4 isolates are H9N2 but for two of the isolates the PB2 gene is half human and half avian.  Thus, a dual infection of human and avian not only reshuffled the 8 genes, but also created new genes (the N2 in the isolates is also a recombinant between 2 Korean H9N2 parents).

An H5N1 with a human binding domain from H1 or H3 would be easily transmitted from human to human, but still retain its very high lethality. 

The H5N1 in asymptomatic ducks increases the size of the gene pool for these very lethal genes and increases the likelihood of a recombined H that has the transmissibility of human influenza combined with the lethality of H5N1.  Such a recombinant would have true pandemic potential.
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