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Rapid Evolution in Qinghai Lake Migratory Bird Flu H5N1
Recombinomics Commentary
July 28, 2005
China has reported no outbreak of human cases. But Dr Chan, formerly Hong Kong's director of health, who helped contain the 1997 Avian influenza outbreak in the city state, and the outbreak of severe acute respiratory syndrome (SARS) in 2003, said, "We will not give up on our efforts. We owe it to the world, because when we talk of pandemic influenza risk it is a global health security issue. To that extent, we will continue our efforts in order to help us to understand the evolution of the virus."
The situation in China, she said, "is very serious . . . and that's why we have not shied away from working very closely with the government to give us specimens."
The need for additional specimens from Qinghai Lake is clear. China only collected samples from 12 dead birds, 10 bar-headed geese, a great black headed gull, and a brown headed gull. The sequences from all 12 isolates were very similar. They all have acquired the human PB2 polymorphism E627K, which had not been seen previously in a H5N1 isolate from a bird. All prior H5N1 with that change had common form mammals, including humans. Virtually all humans infected with a virus containing E627K had died, suggesting the Qinghai isolates have the potential for being lethal in people also.
Analysis of the sequences revealed many polymorphisms normally found in European isolates, offer genetic evidence that the birds at Qinghai Lake were infected with recombinants between viruses in Europe and Asia. The recombinations happen via dual infections, and one of the 10 bar headed geese had evidence of two infections. Since the Hong Kong / Shantou group had sequenced all 10 bar-headed geese, the two geese sequences deposited by the Beijing group represented independent isolates from the same birds (the number and naming by the two groups is slightly off. China called its geese isolates black headed geese while Hong Kong / Shantou called them bar-headed geese, but there was only one species of geese tested so the Beijing isolates were from the same birds as two of the Hong Kong / Shantou isolates). However, one of the Beijing isolates, A/black headed goose/Qinghai/1/2005, had four polymorphism at the 5' end of the HA genes that were not found in the other Qinghai isolates. Instead they were in isolates from Hong Kong, A/Ck/HK/2133.1/2003, or Guangdong, A/duck/Guangdong/173/04 indicating the Qingahi isolate was a recombinant. However, the recombinant was from one of the geese that also had the common sequence, indicating dual infection was present in this bird.
More analysis will likely show that such complexity exists in more birds because many of the submitted sequences coded for non-functional proteins suggesting additional isolates coding for functional proteins were present in these birds. Thus more research was required in both the birds that died initially, as well as birds that were preparing to leave, because these birds probably contain more recombinants, which will soon arrive in areas to the east, south, and west, of the summer location.
China's refusal to collect and share samples is scandalous and jeopardizes almost all neighboring countries. Moreover, boxun reports suggest there have been associated human cases in Qinghai and possibly Xinjiang, Sichuan, and Yunnan, increasing concerns that China is covering up a raging flu pandemic.
Instead of accellerating sample collection. China shut down the Shantou lab and stone-walled requests for sequences and samples.
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