Paradigm Shift Intervention Monitoring
twitter
Live feed of underlying pandemic map data here
Commentary
Selection of pH1N1 D225G In Swine Lung
Recombinomics
Commentary 20:17
April 12, 2010
The above comments are from the PLOS paper, “Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs”, which describes the selection of D225G in swine lung. The swine were initially infected with a pH1N1 mixture at positions 225 and 226. The 226 change, Q226R, was strongly selected against and not found in any of the swine isolates. However the mixture at position 225 was maintained in the upper respiratory tract of the infected swine. Contact swine isolates selected for D225, while the lungs of inoculated swine initially had a mixture, while selection produced D225G at later dates, post infection.
These results match sequence analysis from patients. In the Duke death cluster, isolates from the initial collection had a mixture of D225 and D225G, while a subsequent collection yielded D225G alone. Similarly, samples from the upper and lower tract of the same patient in Hong Kong, had D225 dominating in the upper respiratory tract, but D225G outcompeted wild type in the lower tract. Moreover, many direct sequences from autopsy lung in Ukraine had D225G alone or as a mixture with D225N or wild type.
The in vivo data demonstrated strong selection, which created different combinations of detected polymorphisms in the absence of new “mutations”. The virus with Q226R was selected against, so D226R was not found in any of the isolates. In the transmitted sequences, only wild type was found, even though the infecting swine had both D225 and D225G. Similarly, the lungs from the infected swine initially had a mixture at position 225, but a week after infection only showed D225G (tracing for each of these combinations are seen here) even though lung has 2,3 and 2,6 receptors.
These in vivo data also support selection of a pre-existing sequence in egg isolates. Thus, the original California isolates from propagation in mammalian cells (MDCK) failed to reveal D225G, but growth on eggs had both D225G and Q226R. However, other egg isolates have neither, indicating mere growth in eggs does do automatically create D225G and Q225R, even though that combination was found in A/California/7/2009 and A/Texas/4/2009.
Thus, the detection of D225G in egg isolates does not distinguish between new “mutations” / lab artifact, and simple selection of a minor species, just as detection of wild type in swine infected by contact does not mean that D225G was not present in the infecting swine, or as a minor comp[onent in the infected swine.
The detection of D225G is important, based on its strong association with severe and fatal cases, as well as its presence in 2 of 5 isolates from 1918/1919, and the assumption that D225G in egg isolates is due to de novo mutations or lab artifact has no scientific basis.
Media Links
Recombinomics
Presentations
Recombinomics
Publications
Recombinomics
Paper
at Nature Precedings