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Commentary
D225G
D225N G158E Pseudospecies in Fatal Japan pH1N1 Case
Recombinomics
Commentary 17:56
April 20, 2010
/serotype="H1N1"
/isolation_source="gender:M; age:33; Autopsy lung"
/note="HA-Major (detected at 75%)"
The above description is from one of three HA sequences from the same patient. The initial sequence was deposited by NIID Japan at GISAID last year and had D225G. The two more recent sequences were deposited at Genbank. The above deposit had mixed signals at position 158 and 225. At 158, G158E was mixed with wild type. At position 225, mixed signals were at codon positions one and two, coding for D225G and D22GN. In the third sequence, representing a minor (25%) species, there was G158E and D225N.
These data were all from the same patient (33M), who tested negative for H1N1 and was not treated with oseltamivir. pH1N1 was identified in autopsy lung, which has been described in the publication, “The first autopsy case of pandemic influenza (A/H1N1pdm) virus infection in Japan: detection of a high copy number of the virus in type II alveolar epithelial cells by pathological and virological examination”. Another paper in PLOS One is in press.
These data raise serious questions about the sequences placed on deposit in public databases. The pseudospecies at positions 158 and 225 are common, and vary by sample location and collection from the same patient. Sequences containing both D225G and D225N from fatal cases have been deposited from Ukraine, Moldova, Mexico, and the United States.
In addition, sequences from fatal cases in the Duke death cluster had various combinations. The index case had D225G with wild type in the first collection, and just D225G in the subsequent collection. Another fatal case had D225N with wild type, while a third case was just wild type. However, all of these cases were infected with the same pH1N1 which had the rare HA polymorphism, Y233H, as well as NA H274Y. There is little doubt that all three fatal infections had wild type, D225G, and D225N and various ratios in various collections.
However, in the WHO paper on D225G, the absence of D225G in some direct sequences was used to confuse the D225G situation. Moreover the CDC stated that they had found D225G in only 7 or 8 patients, when they had published D225G sequence from more than 15 patients, suggesting they were discounting samples with D225G in favor of those with wild type. Neither the CDC nor WHO has acknowledged the presence or transmission of D225G or D225N in the Duke death cluster, or any other clusters.
These denials, and the selective release of sequences from patients infected with HA contain D225G and/or D225N continues to be hazardous to the world’s health.
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