Association of D225G/N With Severe H1N1 Cases In Norway



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H1N1 Consulting Paradigm Shift Viral Evolution Intervention Monitoring Vaccine Screening Vaccine Development Expression Profiling Drug Discovery Custom Therapies Patents	Audio:Jan21 Feb2 Feb13 Feb18 twitter Live feed of underlying pandemic map data here Commentary Association of D225G/N With Severe H1N1 Cases In Norway Recombinomics Commentary 21:54 March 4, 2010 Here we report the occurrence of an amino acid substitution, aspartic acid to glycine in position 222 (D222G) in the HA1 subunit of the viral haemagglutinin, in clinical specimens from 11 out of 61 cases analysed in Norway with severe outcome. Such mutants were not observed in any of 205 mild cases investigated (Table), thus the frequency of this mutation was significantly higher in severe (including fatal) cases (p<0.001, Fisher’s exact test, two-sided) than in mild cases. D222G mutants were detected throughout the sampling period, from the first recorded severe cases in July until early December. The frequency of another substitution in the same position, D222E, did not differ significantly between mild and severe cases (p=0.772). Yet another substitution, D222N, was observed in a very few cases (n=4), and at a higher rate than expected among severe cases (three of four cases, p=0.039). The wild type 222D was, not surprisingly, significantly less frequent in severe than in mild cases (p<0.001). In several of the patients where D222G mutant viruses were found, they coexisted with wildtype 222D viruses. Further analysis of this phenomenon is ongoing. The above comments from a report from Norway in Eurosurveillance confirm that D225G/N (H3 numbering) is significantly more common in severe cases in Norway. These data support sequences released by Mill Hill from fatal cases in Ukraine, as well as fatal cases in Russia, which raises concerns that a third wave with a higher frequency of D225G/N would produce a higher incidence of severe and fatal cases. This concern is increased by the designation of a Ukraine isolate with D225G as a low reactor. The levels of D225G/N in severe and fatal cases in Norway, Ukraine, and Russia are in marked contrast to D225E, which is common in several western European countries, including UK, Spain, and Italy, which discounts the possibility that these position 225 polymorphisms are due to copy errors. Instead, the multiple genetic backgrounds that are shared with wild type sequences strongly supports movement of D225G by recombination. D225G has also been found with low reactor polymorphisms in Russia and Italy. The above report also supports the common finding of D225G as a mixture, either with wild type, D225N, or both. Media Links Recombinomics Presentations Recombinomics Publications Recombinomics Paper at Nature Precedings

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