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Commentary
PB2 E627K In Experimental H1N1 Raises Concerns
Recombinomics
Commentary 20:51
March 18, 2010
replication of the virus and diminish the histopathological consequences of infection. Our findings suggest that if the 2009 pandemic virus were to acquire these changes, greater virulence would be an unlikely consequence.
The above comments are from the paper, The PB2 E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase. The results in the paper have been cited in comments on the recent report of a PB2 alternation in pandemic H1N1 from three patients in India. Although the paper provides data showing the E627K can impair replication and pathology of a virus containing the ribo-nuclear protein (RNP) complex (PB2, PB1, PA, NP) from A/California/04/2009, on a seasonal H1N1 genetic background from A/New York/312/2001, there is no data comparing the actual pandemic virus with and without E627K.
Since E627K has been reported in H1N1 from three patients in India, the above reductions in the experimental reassortant lack relevance to pandemic H1N1 because it is unlikely that a virus with significantly impaired ability to replicate would be transmitting as seen in the E627K positive H1N1 in India. Thus, the experimental findings are not predictive of the results of the effect of the acquisition of E627K on pandemic H1N1, and there is no data from a predictive model to support comments on E627K on pandemic H1N1 virulence.
The use of data from experimental models which are not predictive of clinical data are continuously cited by WHO and consultants to discount actual data, which was also done for D225G after the extraordinary high frequencies had been reported in samples from fatal or severe cases.
Both E627K and D225G were found in fatal 1918 cases. E627K has been found in all human seasonal flu since 1918, and D225G was in 2 of the 5 fatal samples from 1918/1919. This historical data has relevance to the 2009/2010 pandemic, which also involves the jump of swine H1N1 to a human population. The presence of E627K in all prior seasonal flu’s signals strong selection pressure by human hosts and suggests the number of pandemic H1N1 infections with E627K will increase, which could lead to increased levels of pandemic H1N1. These increased levels can lead to more efficient transmission in a human population that is no longer naïve. Similarly, a higher viral load can increase the level of H1N1 in the lung, especially if the virus also has D225G/N.
These adaptations to a human host continue to be cause for concern, experimental models notwithstanding.
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