.
Scandalous Lack of H5N1 Migratory Birds Sequences from Qinghai
Recombinomics Commentary
June 28, 2005
>> The Geneva-based arm of the United Nations also wants China to share the gene sequence for the virus that killed the birds in Qinghai to determine whether it's different or more threatening to humans than strains found elsewhere in the region.
There were 189 species of birds on the island, but Chinese officials had tested only five, the WHO and FAO experts said.
The migratory birds are still on the island but will begin flying to other parts of China and neighbouring countries in about a month.
China has requested international assistance but WHO and FAO officials are still waiting for the Government to give approval to carry out tests.
The species known to be infected are the bar-headed goose, great black-headed gull, brown-headed gull, ruddy shelduck and great cormorant. <<
The above comments from various reports on today's WHO media conference begin to address the need for a major sequencing effort in Qinghai Lake and associated outbreaks in Xinjiang. All three OIE reports by China indicated the mode of transmission was migratory waterfowl and evidence is mounting that waterfowl not only transmit H5N1 over long distances, but they can act as mixing vessels to generate novel viruse via reassortment and recombination.
Both reassortment and recombination require dual infections in the same host. Reassortment swaps one or more of the 8 segmented genes of influenza. This swapping does not create new genes, but allows for new constellations of genes. The widely disperse Z genotype represents one such constellation generate via reassortment. The evidence for reassortment is overwhelming. In 1997 the H5N1 isolated from patients in Hong Kong had N and H genes similar to those of the first H5N1 isolate in China, which came from a goose in Guangdong in 1996. However, several of the "internal" genes derived from H9N2 and H6N1 isolates. H9N2 and H6N1 are more benign versions of influenza A and can be found in migrating birds.
Additional evidence for dual infections involving viruses from migrating birds came from H9N2 isolates with H5N1 internal genes as well as H5N1 isolates with H9N2 internal genes. These reassortant provided more support for dual infections. Additional reassortment led to the Z+ genotype found in 2003 patients in Hong Kong, as well as Z genotype constellations found throughout Asia in 2004, including human isolates from Vietnam and Cambodia.
Isolates from fatal human cases were used to infect laboratory ducks, which supported growth of high levels of H5N1 in their intestines, but the ducks were not ill. They excreted usually stable H5N1 and WHO issued a warning about asymptomatic ducks spreading H5N1 that was lethal to humans. In 2005 there was widespread evidence for asymptomatic ducks in southern Vietnam and a survey of all 11 provinces in the Mekong Delta indicated 71% of ducks were H5N1 positive, as were over 21% of chickens. Recent reports indicated asymptomatic ducks were also in northern Vietnam, although the isolates in northern Vietnam were recombinants between the 2004 isolates in Vietnam and 2003 or 2004 isolates from China and Japan.
Thus, a variety of genotypes were capable of growing in ducks asymptomatically and recent reports of H5N1 in duck meat imported by South Korea from Shanghai or Japan from Shandong suggest asymptomatic ducks are present throughout China. H5N1 that do not make domestic ducks ill also probably do not make migratory waterfowl ill either, and can therefore be widely spread.
Moreover, there can be significant mixing of genetic information via recombination. In recombination the genetic information is swapped within a given gene. This swapping creates new genes. New genes appear each season and create new problems. The isolates from northern Vietnam contain a HA cleavage site found in China and Japan. There is evidence for recombination each season, although genetic stability is higher during a given season because the dominant genotype is widespread and dual infections by closely related isolates produces little change because the genomes are genetically similar.
The waterfowl offer an unprecedented opportunity for gathering gene sequence information on migratory waterfowl. Qinghai Lake is in the intersection of the two major flyways in Asia. It is likely that H5N1 will be isolated in many species. H5N1 was readily isolated from geese in Qinghai as well as the two outbreaks in domestic geese in adjacent Xinjiang. These sequences will offer unique insight into how the gene pools of H5N1 mix and create new sequences. Although there are no 2005 H5N1 public sequences at GenBank, some will be deposited and there is a large database of 2004 H5N1 sequences as well as significant sequences from earlier years.
These sequences will allow for predicting the newly emerging sequences for next season.
The opportunity to gather sequences data at Qinghai Lake Nature Reserve should not be lost.
Media sources