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Commentary
Emergence
of Novel H1N1 Raises Pandemic Concerns
Recombinomics
Commentary 20:31
July 22, 2010
The recently released swine H1 sequence from Illinois, A/swine/Illinois/03037/2010, has increased concern that the strain is rapidly spreading and evolving in the Midwestern United States.
Like the two sequences from earlier collections, A/swine/Illinois/0984/2010 and A/swine/Iowa03032/2010, positions 157 and 158 were duplicated, which likely lead to a significant selection advantage. Positions 156-159 (KKGN) in pH1N1 are in a region which is involved in immunological recognition. All CDC designated “low reactors” in US isolates have a change at position 159. Both the CDC and Mill Hill have designated German isolates with G158E as “low reactors. Similarly, MedImmune found that pandemic isolates with G158E grew well in chicken eggs but had a markedly reduced titer when tested with anti-sera directed at wild type sequences. Moreover, immunological escape mutants had changes at these positions. Thus, it is likely that the change of KKGN to KKEN followed by a duplication to produce KKEKEN, leads to a significant reduction in immune recognition in swine, leading to a selective advantage.
The two most recent H1N1 isolates in swine that were not pandemic H1N1 had the duplication. Both isolates were collected in June, 2010 (in Iowa and Illinois) and suggest that this strain is rapidly spreading.
This duplication is on a genetic background most closely related to swine and human isolates from a Hudson County fair in Ohio in August, 2007. In addition to the isolates from a presenter (10F) and her father (36M), 24 attendees had flu-like symptoms, indicating the strain was readily transmitted from swine to humans, but the transmission was not sustained and did not lead to a pandemic.
However, the duplication at positions 157 and 158, combined with recent genetic acquisitions from pH1N1 raises concerns that efficient transmission in humans may develop in the near term. pH1N1 is also widespread in Midwestern swine, as is H1N2, which has a human seasonal H1.
The co-circulation of two distinct triple reassortants with a North American swine H1 allow for rapid evolution via recombination. Most of the newly acquired polymorphisms in pandemic H1N1 trace back to North American swine, and many of the new polymorphisms in the H1N1 with the duplication trace back to pH1N1. This two way exchange of genetic information via recombination leads to rapid evolution , which may include efficient transmission in humans. Both H1N1 strains readily transmit in swine, while pH1N1 readily transmits in humans. Moreover, the frequency of low reactors in pH1N1 was on the rise in the spring of 2010.
The co-circulation of a human adapted H1N1 with a swine H1N1 raises concerns sequences with extensive recombination will emerge in 2010, as happened in 1918.
More aggressive surveillance of H1N1 in swine worldwide is warranted, as is increased sequencing of human H1N1, since PCR testing may not distinguish between the two swine H1N1 strains.
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