Molecular epidemiology of human cluster

There are now 8 complete genomes associated with the human outbreak. 5 are from human cases, 3 from birds or environmental samples. The general picture remains that the internal genes are likely from avian H9N2 viruses circulating in the area but the HA and NA are not similar to any of the viruses sampled so far. The HA groups with a few H7N3 viruses but the divergence is such that this doesn't give us much information about the immediate origins of this segment. Likewise, the NA groups with some H7N9 viruses from Korea but again, the divergence is large.

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 structure of internal gene segments

Outline: generally the 8 genomes belonging to the outbreak group together and have similar relationships with each other (see the PB2 tree for a representitive example). There are 3 notible exceptions to this: 1) in PA (segment 3) the most recently posted isolate, A/Zhejiang/DTID-ZJU01/2013, is more basal and falls outside some of the background avian strains. 2) in NP (segment 5), A/Shanghai/1/2013 is more basal and falls outside some of the background avian strains and the A/Pigeon/Shanghai/S1069/2013 is more divergent from the other outbreak viruses. 3) Finally, in M1/2 (segment 7) the A/Environmental/Shanghai/S1088/2013 is the most divergent of the outbreak strains.

All of this suggests a relatively diverse population of viruses in the reservoir with ongoing mixing and reassortment with circulating H9N2 avian viruses. 

Segments 1 & 2

PB2:

PB2_local.tree.png

PB1:

PB1_local.tree.png

In these two segments the outbreak viruses (labelled in red) have very consistent phylogenetics relationships both with each other and with the background avian virus - A/brambling/Beijing/16/2012 is the closest relative.

Segment 3

PA:

PA_local.tree.png

Here things get a little bit more complicated with the PA of A/Zhejiang/DTID-ZJU01/2013 lying basal to the A/brambling/Beijing/16/2012 suggesting reassortment. 

Segment 5

NP:

NP_local.tree.png

Likely evidence  that both A/Pigeon/Shanghai/S1069/2013 and A/Shanghai/1/2013 have reassorted NP segments here.  The brambling is also more distantly related here.

Segment 7

M1/2:

MA_local.tree.png

The internal structure of the outbreak is consistent with most of the segments but the closest background viruses in the other segments are more distant here (note the brambling).

Segment 8

NS:

NS_local.tree.png

Once again, same internal structure but different relationships with the background viruses.

Segment 4

HA:

HA_H7Nx_local.tree.png

Although they group somewhat distantly from some duck H7N3 viruses, the internal relationships of the outbreak clade remains similar to PB2 & PB1

 

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