Avian Influenza H7N9, human cases, Shanghai, China - Molecular Evolution and Origins

We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiFlu™ Database on which this analysis is based. A list of the sequences, their submitting labs and GISAID links is provided on this page.

Phylogenetic Analysis

Maximum likelihood phylogenetic trees (Phyml, HKY+G) for each gene segment using closest matches in NCBI. Rooted with temporal information using Pathogen. The general pattern is that the internal genes group (segments 1, 2, 3, 5 & 7) with reasonably local, predominantly chicken H9N2 isolates, segment 4 with some 2011 Chinese duck H7N9 viruses and segment 6 with 2011 Korean H7N9 from wild birds. Both these last two are quite divergent from these relatives suggesting lack of sampling of local source of the human strain but it is likely to be a H7N9 reassortant with internal genes from H9N2 viruses. 

In all segments A/Shanghai/2/2013 groups with A/Anhui/1/2013 to the exclusion of A/Shanghai/1/2013 but in NP the common ancestor of the 3 is older suggesting perhaps a further reassortment of a more divergent NP gene at some point in one or other of the lineages. This suggests that the A/Shanghai/1/2013 sequence is may the result of a separate zoonosis from a bird lineage with a slightly divergent NP.

Segment 1 - PB2 Gene

PB2.phyml.path.tree2.png

New 2013 human cluster highlighted in blue. Although this is a H7N9 virus, in many of the gene segments including PB2, above, it clusters with Avian H9N2 viruses suggesting a recent reassortment. Whether this is directly associated with the emergence in humans or just a feature of the viruses circulating in birds in the area remains to be seen. The yellow group of viruses have been highlighted in  the same colour for PB1 and PA, below, demonstrating more reassortment in these bird viruses.

Segment 2 - PB1 gene

PB1.phyml.path.tree2.png

New 2013 human cluster highlighted in blue. PB1 gives a similar position as PB2, above, with the closest isolate being the same H9N2 avian from 2012 (A/brambling/Beijing/16/2012). The mauve group of viruses can be seen as the closest neighbors of the human cluster in NP, below.

Segment 3 - PA gene

PA.phyml.path.tree2.png

New 2013 human cluster highlighted in blue. PB1 gives a similar position as PB1 & PB2, above, with the closest isolate being the same H9N2 avian from 2012 (A/brambling/Beijing/16/2012).

Segment 4 - HA gene

HA.phyml.path.tree2.png

New 2013 human cluster highlighted in blue. In HA, above, they cluster with a few H7N3  avian viruses within a larger cluster of various H7 avian viruses. 

Segment 5 - NP gene

NP.phyml.path.tree2.png

New 2013 human cluster highlighted in blue. NP clusters with H9N2 chicken sequences but note the very divergent branch of A/Shanghai/1/2013 from the other two human cases (which are identical). 

Segment 6 - NA gene

NA.phyml.path.tree2.png

New 2013 human cluster highlighted in blue. In NA, above, they cluster with a few H7N9  avian viruses within a larger cluster of H11 avian viruses. 

Segment 7 - M1/2 gene

MP.phyml.path.tree2.png

Segment 8 - NS1/2 gene

NS.phyml.path.tree2.png

The closest sequence is A/chicken/Dawang/1/2011 in green. In PB1 and PB2 this is found much further away. 

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