Fig 1.
Phylogenetic tree analysis of the origins of HA and NA segments of the H7N4 human isolate in China.
A) 35 HA segments of H7 isolates were analyzed using MEGA6 software. Magenta: new H7N4 viruses including A/Jiangsu/1/2018 (JS2018); Cyan: related avian H7N7 viruses; Black: H7N1, H7N2, H7N3, H7N5, H7N6, H7N7 (human), H7N8 and H7N9 viruses. A/red not/NJ/321/1989 (H13N4), A/shorebird/Korea/S303/2006 (H11N4) and A/chicken/Jiangsu/YB7/2015 (H5N1) isolated in Jiangsu were used as outgroup control strains. Scale bar indicates the amount of substitutions in the nucleotides. B) 35 NA segments of N4 isolates were analyzed using MEGA6. Magenta: H7N4 viruses including JS2018; Cyan: related avian H8N4 viruses; Black: H1N4, H2N4, H3N4, H4N4, H5N4, H6N4, H8N4, H9N4, H10N4, H11N4, H12N4, H14N4, and H15N4 viruses. Outgroup controls: A/chicken/Jiangsu/YB7/2015 (H5N1) and A/duck/Chiba/25-51-14/2013 (H7N1). Scale bar: the amount of nucleotide substitutions.
Fig 2.
Phylogeny of the origins of PB2, PB1, PA, NP, M and NS segments of the novel H7N4 virus from H7N7, H8N4, and H5N1 viruses.
The internal segments of the viruses were aligned and subjected to the construction of phylogenetic trees. The viruses included JS2018, A/chicken/Jiangsu/1/2018, A/duck/Jiangsu/4/2018, H7N7, and H8N4 strains identified in Fig 1, and representative avian H9N2 strains as well as human H5N1, H7N9, H7N2 and H9N2 viruses, collected in mainland China between 1994 and 2017. A) PB2; B) PB1; C) PA; D) NP; E) M; and F) NS. H7N4 viruses (magenta) and related H7N7, H8N4 and H5N1 viruses (cyan) were highlighted. For each segment, the scale bar indicates the number of nucleotide substitutions. The human H7N3 virus (A/Canada/rv504/2004 (H7N3)), which was never identified in Europe and Asia, was used as outgroup control.
Fig 3.
Probable multi-reassortment of the novel human H7N4 virus.
For JS2018, the PB2, PA, HA, NP, and NS segments (magenta) were avian H7N7-derived; The NA and M segments (cyan) were donated by an avian H8N4 virus; PB1 (green) was likely obtained from an avian H5N1 virus. Remarkably, none of these internal segments was acquired from any known regional H9N2 viruses (grey). Possible migratory route of birds carrying H7N7 or H8N4 viruses was shown in arrows in the map. Magenta dot: Gunma (Japan), Kumamoto (Japan), Jiangxi (China). Cyan dot: Chany (Russia). Green dot: Changzhou, Jiangsu (China). Yellow dashline: the East Asia-Australia migratory flyway.
Table 1.
Molecular features of the human and related domestic avian H7N4 isolates compared to human H7N9 and H5N1 strains.
Table 2.
Whole-genome mutations in the human H7N4 isolate compared with related H7N4 avian isolates and human H7N9 and H5N1 isolates.