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Case Reports
. 2014 Jul;69(1):60-8.
doi: 10.1016/j.jinf.2014.02.012. Epub 2014 Feb 24.

Unique reassortant of influenza A(H7N9) virus associated with severe disease emerging in Hong Kong

Kelvin Kai-Wang To  1 , Wenjun Song  2 , Siu-Ying Lau  2 , Tak-Lun Que  3 , David Christopher Lung  3 , Ivan Fan-Ngai Hung  4 , Honglin Chen  1 , Kwok-Yung Yuen  5
Affiliations
Case Reports

Unique reassortant of influenza A(H7N9) virus associated with severe disease emerging in Hong Kong

Kelvin Kai-Wang To et al. J Infect. 2014 Jul.

Abstract

Objective: Human infections caused by avian influenza virus A(H7N9) re-emerged in late 2013. We reported the first Hong Kong patient without risk factors for severe A(H7N9) disease.

Methods: Direct sequencing was performed on the endotracheal aspirate collected from a 36-year-old female with history of poultry contact. Bioinformatic analysis was performed to compare the current strain and previous A(H7N9) isolates.

Results: The influenza A/Hong Kong/470129/2013 virus strain was detected in a patient with acute respiratory distress syndrome, deranged liver function and coagulation profile, cytopenia, and rhabdomyolysis. The HA, NA and MP genes of A/Hong Kong/470129/2013 cluster with those of other human A(H7N9) strains. The PB1, PB2 and NS genes are most closely related to those of A/Guangdong/1/2013 strain identified in August 2013, but are distinct from those of other human and avian A(H7N9) strains. The other internal genes NP and PA genes are more closely related to those of non-A(H7N9) avian influenza A viruses. A unique PA L336M mutation, associated with increased polymerase activity, was found. The patient required salvage by extracorporeal membrane oxygenation.

Conclusions: The A/Hong Kong/470129/2013 virus is a novel reassortant derived from A/Guangdong/1/2013 virus. The unique mutation PA L336M may enhance viral replication and therefore disease severity.

Keywords: Avian influenza; Evolution; H7N9; L336M; PA; Phylogenetic tree.

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Figures

Figure 1
Figure 1
Phylogenetic trees showing the relationship of A/Hong Kong/470129/2013 to other A(H7N9) and non-A(H7N9) avian influenza viruses. (A) HA1. (B) NA. (C) PB2. (D) PA. (E) PB1. (F) NP. (G) NS. (H) MP. The phylogenetic trees were constructed using neighbour-joining method with Tamura-Nei model of nucleotide substitution using MEGA software package, version 5.05. The bootstrap values from 1000 replicates were performed to evaluate the reliability of the phylogenetic trees. The A/Hong Kong/470129/2013 was highlighted in bold font in red, while other human A(H7N9) strains were highlighted in blue. Sequences not determined in this study were obtained from NCBI Influenza Virus Resource database, except A/Anhui/1/2013 and A/Shanghai/1/2013 which were obtained from Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu™ Database (Supplementary Table).
Figure 1
Figure 1
Phylogenetic trees showing the relationship of A/Hong Kong/470129/2013 to other A(H7N9) and non-A(H7N9) avian influenza viruses. (A) HA1. (B) NA. (C) PB2. (D) PA. (E) PB1. (F) NP. (G) NS. (H) MP. The phylogenetic trees were constructed using neighbour-joining method with Tamura-Nei model of nucleotide substitution using MEGA software package, version 5.05. The bootstrap values from 1000 replicates were performed to evaluate the reliability of the phylogenetic trees. The A/Hong Kong/470129/2013 was highlighted in bold font in red, while other human A(H7N9) strains were highlighted in blue. Sequences not determined in this study were obtained from NCBI Influenza Virus Resource database, except A/Anhui/1/2013 and A/Shanghai/1/2013 which were obtained from Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu™ Database (Supplementary Table).
Figure 1
Figure 1
Phylogenetic trees showing the relationship of A/Hong Kong/470129/2013 to other A(H7N9) and non-A(H7N9) avian influenza viruses. (A) HA1. (B) NA. (C) PB2. (D) PA. (E) PB1. (F) NP. (G) NS. (H) MP. The phylogenetic trees were constructed using neighbour-joining method with Tamura-Nei model of nucleotide substitution using MEGA software package, version 5.05. The bootstrap values from 1000 replicates were performed to evaluate the reliability of the phylogenetic trees. The A/Hong Kong/470129/2013 was highlighted in bold font in red, while other human A(H7N9) strains were highlighted in blue. Sequences not determined in this study were obtained from NCBI Influenza Virus Resource database, except A/Anhui/1/2013 and A/Shanghai/1/2013 which were obtained from Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu™ Database (Supplementary Table).
Figure 1
Figure 1
Phylogenetic trees showing the relationship of A/Hong Kong/470129/2013 to other A(H7N9) and non-A(H7N9) avian influenza viruses. (A) HA1. (B) NA. (C) PB2. (D) PA. (E) PB1. (F) NP. (G) NS. (H) MP. The phylogenetic trees were constructed using neighbour-joining method with Tamura-Nei model of nucleotide substitution using MEGA software package, version 5.05. The bootstrap values from 1000 replicates were performed to evaluate the reliability of the phylogenetic trees. The A/Hong Kong/470129/2013 was highlighted in bold font in red, while other human A(H7N9) strains were highlighted in blue. Sequences not determined in this study were obtained from NCBI Influenza Virus Resource database, except A/Anhui/1/2013 and A/Shanghai/1/2013 which were obtained from Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu™ Database (Supplementary Table).
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