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China H1N1 Sequences Target Lung
Recombinomics Commentary 19:30
January 16, 2014

The WHO Chinese National Influenza Center operated by the Chinese CDC in Beijing released H1, N1, and MP sequences from 27 isolates from Beijing, Shanghai and 11 provinces throughout eastern China.  The samples were collected between September 3 and December 4 from patients who were almost exclusively under 65.  Remarkably, 14 of the sequences were from egg isolates and almost all had at least one of the receptor binding domain changes that target human lung.

The most common marker with high affinity for gal 2,3 receptors (which are dominant in chicken eggs or human lung) was Q226R (
A/Shanghai-Mixing/SWL1660/2013, A/Sichuan-Qingyang/SWL1544/2013, A/Jiangsu-Sucheng/SWL1726/2013, A/Jiangsu-Tinghu/SWL1623/2013, A/Jiangsu-Qinhuai/SWL11396/2013, A/Fujian-Cangshan/SWL1652/2013, A/Guangdong-Chancheng/SWL1583/2013).  Two others had D225G (A/Shanghai-Changning/SWL1568/2013 and A/Chongqing-Yuzhong/SWL11434/2013), which was also seen for L194I (A/Chongqing-Yuzhong/SWL11676/2013 and A/Sichuan-Yucheng/SWL1693/2013).  The latter also had a change at the adjacent position, S193I, while another isolate, A/Sichuan-Wuhou/SWL2259/2013, had the same position changed (to S193R).

The high prevalence of these receptor binding domain changes in the above egg isolates raises concerns that the frequency of these changes is higher in 2013/2014 isolates than 2009, when pH1N1 emerged as a new pandemic.  These changes are also found at high frequency in egg isolates in the United States, but the frequency of sequences from egg isolates is lower in those released by CDC from US cases.

The criteria for the pH1N1 isolate in eggs are unclear.  If samples are placed on both mammalian and egg cells, and sequences representing the H1N1 that grows to highest titers, then the high frequency of egg isolates in China would be cause for concern, because the vast majority of such isolates have polymorphisms that clearly target human lung.  It is likely that the lower frequency of egg isolates in the US reflects collection and isolation criteria, since high levels of severe and fatal cases in the US have been widely reported.

Recent reports from California and Texas indicate the number of ICU and fatal cases in 2013/2014 will surpass reported levels in 2009, and these week 1 reports reflect H1N1 circulating after the cases supplying samples for the released sequences from China and the US. 

More information on criteria for egg isolates in the US and China would be useful.

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