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| Map 1. Human cases and positive findings in birds or the environment |
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It has been just over 8 months since we first learned of the emergence of an HPAI (highly pathogenic) version of the H7N9 virus in China (see Guangdong CDC: Two H7N9 `Variants' Isolated From Human Cases), and while we've seen a smattering of preliminary analyses published over the spring and summer (see here, here, and here ), in the past week the flood gates appear to have opened.
Last week we looked at Cell Host & Microbe: HPAI H7N9 Lethality & Transmission In Ferrets, while yesterday we explored Cell Research: Another Cautionary H7N9 Study Out Of China.Both studies cited HPAI H7N9's rapid acquisition of mammalian adaptations which appear to increase its pandemic potential. Today, we've another study - this time published in the Journal of Virology - which describes the emergence and rapid adaptation of the virus in both birds and humans (note: bolding mine).
Emergence and adaptation of a novel highly pathogenic H7N9 influenza virus in birds and humans from a 2013-human-infecting low pathogenic ancestor
Wenbao Qi1,5,8, Weixin Jia1,5,8, Di Liu2,6,13, Jing Li6, Yuhai Bi2,6, Shumin Xie1, Bo Li1,
Tao Hu4, Yingying Du3, Li Xing1, Jiahao Zhang1, Fuchun Zhang7, Xiaoman Wei3,12, John-Sebastian Eden9,11, Huanan Li1, Huaiyu Tian10, Wei Li6, Guanming Su1, Guangjie Lao1,
Chenggang Xu1,5,8, Bing Xu10, Wenjun Liu6, Guihong Zhang1,5,8, Tao Ren1,5,8, Edward C. Holmes9, Jie Cui3, Weifeng Shi4, George F. Gao2,6,13* and Ming Liao1,5,8*
ABSTRACT
Since its emergence in 2013, the H7N9 low pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections.
Recently, a novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin protein was firstly reported in two human infection cases in January 2017. More seriously, those novel HPAI H7N9 variants have transmitted and caused poultry farms outbreaks in eight provinces.
Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the pre-existing LPAIVs. Animal experiments showed that these novel HPAI H7N9 variants are both highly pathogenic in chickens and lethal to mice.
Notably, human origin viruses were more pathogenic in mice than avian viruses, and the mammalian adaptation associated E627K, A588V, and D701N mutations in the PB2 gene were identified in the infected mice using next-generation sequencing (NGS) and Sanger sequencing. In the key amino acid substitutions of PB2 and HA, no polymorphism was detected in the infected chickens lungs by NGS.
In sum, these results highlight the highly pathogenicity and transmission in chickens, and the quickly adaptation in mammals of this new H7N9 variant, so the risk should be evaluated and payed more attention.
IMPORTANCE
Due to the recent increase zoonotic infections in poultry and persistent human infections in China, influenza A (H7N9) virus has remained a public health threat. Most of the A(H7N9) viruses previously reported have been of low pathogenicity.
Now, these novel H7N9 HPAIV have caused human infection in three provinces and poultry farms outbreaks in eight provinces. We analyze these molecular features and compared the relative characteristics of one H7N9 LPAIV and two H7N9 HPAIVs isolated from chickens and two human-origin H7N9 HPAIVs in chicken and mice models.
Our finding that all HPAIVs are both highly pathogenic and valid transmissibility in chickens. Strikingly, the human-origin viruses were more highly pathogenic than avian-origin viruses in mice, dynamic mutation were confirmed by NGS and Sanger sequencing. Our findings offer important insight into the origin, adaptation, pathogenicity, transmissibility to both poultry and mammals.
While all is apparently quiet on the avian flu front in China right now, winter is on the way, and we shouldn't have too long to wait to see what new surprises H7N9 has in store for us in its 6th epidemic wave.
