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H1N1pdm09 Recombination In Egypt H5N1 Raises Concerns
Recombinomics Commentary 21:00
January 25, 2012

The recently released H5N1 sequences from Egypt contain H1N1pdm09 sequences in the PB1 and PB2 gene segments.  The recent comments by Yoshihiro Kawaoka on the data in the censored Nature paper indicate H5 on an H1N1pdm09 genetic background transmits in ferrets.  Although the paper remains censored, the comments suggest H5 was added to 7 gene segments from H1N1pdm11.  However, an earlier study suggested that the H1N1pdm09 M gene was critical for the jump from swine to humans, so it is unclear if the other six gene segments are required for transmission.

However, the presence of H1N1pdm09 gene sequences in the H5N1 isolates raise concerns that additional combinations are likely and the status of such combinations are far from clear.  The most recent human H5N1 sequence from Egypt are from cases in March 2010.  More recently, clusters in Egypt have been confirmed and an increased case fatality rate has been noted, raising concerns that H1N1pdm09 internal genes may be present in human cases in Egypt.

NAMRU-3 typically generates H5 and N1 sequences for human cases in Egypt, while samples are frequently sent to the CDC in Atlanta for further analysis.  These sequences should be released immediately.  The presence of such sequences may signal and enhanced transmission in humans and may be related to the confirmation of clusters.

Although the H5 transmission in ferrets in the Kawaoka study did not produce a lethal H5N1 in the ferret model, the wide circulation of such sequences in human populations could have significant implications, as has been demonstrated for the H1N1pdm09 M gene in trH3N2 (H3N2v) and trH1N1 (H1N1v) cases in the United States in 2011.

The Kawaoka Nature paper highlights the need for full sequences from cases in Egypt.  This need applies to other recent cases, such as the clusters in Indonesia.  Only HA and NA sequences were released from the Bali cluster, which also had clear evidence of recombination.  Similarly, no sequence data has been released for the cluster in North Jakarta.

The censored papers at Nature and Science highlight the dangers of a transmitting H5N1 and demand more timely and transparent release of H5N1 sequences.

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