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Commentary
H1N1 PB2 E627K In
Three Patients In India
Recombinomics
Commentary 05:36
March 16, 2010
The PB2 mutation has previously been associated with increased efficiency of replication and possible virulence changes in other influenza A viruses.
The above comments indicate E627K has been detected in three patients in India. E627K has been found in all human influenza since 1918, so acquisition of the polymorphisms is not a surprise. Some had speculated that it would be acquired from seasonal flu via reassortment, but there have been no reports of any change in the original constellation of genes in pandemic H1N1, which had only one human flu gene, PB1, which was acquired in 1993. The above description indicates the acquisition was a single nucleotide change and was likely due to recombination. The finding of the same change in three patients indicates E627K is transmitting. Prior reports of one isolate in Shanghai or two isolate in The Netherlands did not lead to additional reported transmissions. However, the simultaneous detection in three patients in India suggests the E627K will become widespread.
Multiple reports in the US are signaling recent upticks in H1N1 cases, and it is likely that the new wave will select multiple changes. Increasing rates of acquisitions have been noted, including D225G/N and G158E in HA as well as H274Y in NA.
These recent acquisitions raise concerns of increases in severe and fatal cases. The acquisition of E627K will likely lead to higher levels of H1N1, which would also create more severe cases. E627K allows for more efficient replication at lower temperatures which is linked to more efficient transmission via the upper respiratory tract, while additional HA changes lead to higher levels of H1N1 in lung. Many of the significant polymorphisms have been associated with mixtures, and a mixture of PB2 with E627 and E627K could lead to increases in transmission as well as increases in lethality.
Sequence data in these three patients and relationships to each other would be useful.
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