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Novel H7N9 Hong Kong Ex-Shenzhen - H7 Human Adaptations
Recombinomics Commentary
December 30, 2014 23:00

The sequences from the first confirmed  H7N9 case (68F) in Hong Kong in the 2014/2015 season, A/Hong Kong/8194273/2014, raised concerns due to evidence of human adaptation in four recently acquired internal genes.  The PB2 sequence is most closely related to avian H9N2 sequences, except it has the human adaptation E627K.  In addition, two other internal genes (PB1 and NP) are closely related to the human H9N2 case (86M) in late 2013, A/Hong Kong/308/2014, while the PA sequence is closely related to the human H10N8 sequence, A/Jiangxi-Donghu/346/2013 (73F, also from late 2013).

However, the H7 sequence also has evidence for human adaption.  Two changes, T160A and Q226L, were present in the initial cases in early 2013.  However, cases from late 2013 and early 2014 were found in geographic or familial clusters, especially those in Guangdong Province.  Although sequences from initial cases were made public, subsequent sequences were withheld, and most sequence data was from cases exported to Hong Kong, as was the case for the first case in the 2014/2015 season.

The H7 sequence belongs to a sub-clade that includes the three most recent sequences from the prior season (A/Hong Kong/8122430/2014, 85F collected 4/13; A/Hong Kong/5731/2014, 82F collected 4/8; A/Hong Kong/5581/2014, 65M collected 4/3) as well as A/Hong Kong/4495/2014, 0.5F collected 3/1; and A/Malaysia/228/2014, 67F collected 2/11). 

This subclade has three non-synonymous changes that are almost exclusively limited to human cases.  E113K is present in the six human H7 sequences above, as well as A/Hangzhou/17-1/2014 and A/chicken/Jiangxi/SD001/2013). L177I is in the six above, plus 2 more human sequences (A/Taiwan/1/2014 and A/Taiwan/2/2014), while N276D is in the six above, plus A/Huizhou/01/2013, A/Guangdong/1/2013, A/shanghai/05/2013, and A/Shanghai/1/2013.  The presence of all three of these polymorphisms in the six member subclade, as well as addition isolates which are almost exclusively human, raises concerns that these three H7 polymorphisms represent further human adaptation.

The first Hong Kong case in 2014/2015 was from Shenzhen, where the first case (35F) in Guangdong province was just reported.  No poultry link was cited for either case, and both have symptomatic contacts, raising concerns that the number and size of clusters this season will be markedly higher than prior seasons.

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