E627K Increases H5N1 Replication at Lower Temperatures
Recombinomics Commentary
October 5, 2007
Birds usually have a body temperature of 106 degrees F, and humans are 98.6 degrees F usually. The human nose and throat, where flu viruses usually enter, is usually around 91.4 degrees F.
"So usually the bird flu doesn't grow well in the nose or throat of humans," Kawaoka said. This particular mutation allows H5N1 to live well in the cooler temperatures of the human upper respiratory tract.
H5N1 caused its first mass die-off among wild waterfowl in 2005 at Qinghai Lake in central China, where hundreds of thousands of migratory birds congregate.
That strain of the virus was carried across Asia to Africa and Europe by migrating birds. Its descendants carry the mutation, Kawaoka said.
"So the viruses circulating in Europe and Africa, they all have this mutation. So they are the ones that are closer to human-like flu," Kawaoka said.
Luckily, they do not carry other mutations, he said.
The above comments on the paper describing PB2 E627K replication in experimental mice and cells highlight the effect of the change on the ability of the Qinghai strain to replicate at lower temperatures.
The detection of E627K in dead wild birds at Qinghai Lake in May, 2005 signaled a major change in the global spread of H5N1. At the time “Asian” H5N1 had not been reported in any country west of China. The massive die-off at Qinghai Lake signaled the movement of H5N1 in long range migratory birds and the strain of a major geographical expansion.
The data on the temperature dependence of E627K also explains why many surveillance programs fail to detect Qinghai H5N1 in live wild birds, including locations where H5N1 is readily detected in dead or dying wild birds. The body temperature of live wild birds keeps the levels of the virus low, below the detection levels of these assays. Dead and dying birds have a lower body temperature, allowing levels of the virus to rise.
Although the effect of E627K on viral replication has been know since 2001, this fact has been ignored in the surveillance programs that focus on live birds. Instead of measuring H5N1 antibody levels, which are more stable and reliable, these groups test thousands of birds and then use the false negatives to issue assurances and denials of the transport and transmission of H5N1 by wild birds.
Consequently, the alarming expansion of Qinghai H5N1 has largely happened below the radar of these surveillance, which remains a cause for concern, as have changes in the receptor binding domain in Qinghai isolates from fatal human cases, including V223I, S227N, and M230I.
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