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Commentary
Widespread
pH1N1 Low Reactors In Europe
Recombinomics
Commentary 19:37
May 6, 2010
The appearance of the same polymorphism on multiple branches signals spread by homologous recombination, while the clustering on specific branches signals spread by clonal expansion. Similar results were seen in a large series in Germany, which followed similar patterns in the United States and Japan.
These increases in low reactors most commonly involve psuedospecies at position 158. Such changes were discussed in the paper describing the selection of a California/7 vaccine target. Isolate with G158E grew well in eggs, reflecting an increased affinity for gal 2,3 receptors. However, G158E was not included because of the marked reduction in titer in antisera directed against wild type California/7. The low reactor linkage to G158E was also seen in escape mutants, which had G158E, as well as testing of German isolates by Mill Hill and CDC. Both labs designated isolates with D158E was “low reactors".
However, subsequent isolates from the US which had G158E were not designated low reactors, suggest a change in antisera by the CDC. This antisera appears to have limited ability to detect low reactors, because all recent US low reactors designated by the CDC have changes at position 159. Positions 157-159 map to the same antigenic sites, and changes at all three positions has been linked to low reactor status or immunological escape.
The failure of the CDC to designate US isolates with G158E as low reactors raises concerns that such important changes are circulating undetected. Since the changes is usually detected as a pseudospecies, the ration of G158E to G158 may vary within the host. Samples from the upper respiratory tract would have higher frequencies of wild type, while lung samples would have higher concentrations of G158E. Thus, the G158E may not be detected in direct sequencing, especially if samples are collected early or from the upper respiratory tract.
The position 158 pseudotypes are similar to position 225 psuedotypes, which also have a component, D225G, which targets the lung. D225G is also increasing dues to recombination and clonal expansion, and the number of sequences with G158E and D225G continue to rise. In the latest series, A/Georgia/4484/2009, collected on Dec 21, 2009 has G158E and D225G.
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