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Commentary
H1N1
G158E and D225G Transmission In Nanjing China
Recombinomics
Commentary 15:26
July 26, 2010
This transmission would increase the number of examples which refute the WHO “working hypothesis” that D225G was “spontaneous” and did not cluster in time and space. The clustering was seen in Ukraine in November, 2009, in advance of the WHO publication in late December, 2009. Moreover, the repeat of the WHO position was e-mailed in January, 2010, just prior to the release of a large series of Ukraine sequences from autopsy lung samples, which extend the observation to time and space clustering for D225G and D225N in Ukraine in November, 2009. Further time and space clustering was seen in Russian sequences from fatal cases in late 2009 as well as familial transmission in Italy. Recent sequences from Singapore include related sequences with D225G which were collected in April, 2010.
The transmission of D225G is not a surprise. Five HA sequences from fatal cases in 1918/1919 have been published and two of the five sequences have D225G. The deaths of 20-50 million people in 1918/1919 left little doubt that pandemic H1N1 was transmitting and the presence of D225G in 2 of the 5 sequences was not a coincidence. D225G has been strongly associated with severe of fatal H1N1 in 2009/2010 and a revision of the WHO/CDC “working hypothesis” is long overdue. The jumping of D225G from one genetic background to another via recombination is consistent with the multiple examples in Ukraine and Russia has seen many times now, and the WHO.CDC silence on this issue continues to be hazardous to the world’s health.
The latest sequences from China increase those concerns. G158E is linked to “low reactor” status as well as preferential growth in cells containing alpha 2,3 receptors, which are in human lung. Pandemic H1N1 clones with G158E were characterized because the change facilitated growth in eggs (which have 2,3 receptors). However, the low reactivity with anti-sera directed against wild type led to the absence of D158E in the pandemic target. This low reactor result was also seen in German isolates characterized by the CDC and Mill Hill. However, the CDC appeared to change its assay for subsequent human isolates from the US, which were not designated as “low reactors” even though D158E was present. The CDC assay for US isolates limited “low reactors” to sequences with changes at the adjacent position, 159. Differences were also seen in sequences with D225G. Mill Hill designated such sequences as “low reactors” although the CDC did not.
Sequences with G158E and G225G were seen at the end of last season in Russia and Greece. Last week’s sequence was the first report of both changes in human isolates in China, although swine sequences from Guangdong province have both changes, raising concerns of acquisition via recombination. The two most recent sequences from Nanjing support such jumps, and the detection of both changes on consecutive sequences collected on June 30, 2010 strongly support transmission of both markers on a genetic background linked to China.
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