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H5 Transmission On H1N1pdm09 Genetic Background
Recombinomics Commentary 19:30
January 25, 2012

To determine whether H5N1 viruses could be transmitted between humans, my team generated viruses that combined the H5 haemagglutinin (HA) gene with the remaining genes from a pandemic 2009 H1N1 influenza virus. Avian H5N1 and human pandemic 2009 viruses readily exchange genes in experimental settings, and those from a human virus may facilitate replication in mammals. Indeed, we identified a mutant H5 HA/2009 virus that spread between infected and uninfected ferrets (used as models to study the transmission of influenza in mammals) in separate cages via respiratory droplets in the air. Thus viruses possessing an H5 HA protein can transmit between mammals.

The above comments by Yoshihiro Kawaoka indicate H5 can transmit in ferrets when constructed on an H1N1pdm09 genetic background, raising concerns that H5 transmission in humans can arrise through multiple mechanisms.  Since the paper at Nature has been censored, it is unclear if only one combination has been tried, but the finding highlights the need for additional studies.

In 2011 the addition of the H1N1pdm09 M gene onto H3N2v genetic backgrounds has generated 12 human isolates including clusters in Iowa and West Virginia, raising concerns that this one gene on an H5N1 background could lead to more efficient transmission.

Moreover, the recently released H5N1 sequences from Egypt have recombined H1N1pdm09 sequences in PB1 and PB2 raising concerns that such acquisitions can lead to more efficient transmission also, although the absence of sequences from any human isolate in Egypt since March, 2010 and the absence of internal gene sequences in earlier isolates limits conclusions.

The comments above make it clear that the full sequences from human cases in Egypt should be released by NAMRU-3 and/or the US CDC immediately, and the censored papers at Science and Nature should also be published in full immediately.

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