Wednesday, October 25, 2017

Cell Research: Another Cautionary H7N9 Study Out Of China











#12,858


Last week's study (see Cell Host & Microbe: HPAI H7N9 Lethality & Transmission In Ferrets) led by Yoshihiro Kawaoka has increased concerns over the pandemic potential of the recently emerged highly pathogenic strain of H7N9 in China.
But as we've discussed before, H7N9 is a multi-faceted threat, with two broad lineages (the newer Yangtze River Delta lineage along with the original Pearl River Delta Lineage), and dozens of genotypes of the virus circulating in poultry and wild birds across a wide swath of China. 
The CDC's Influenza Risk Assessment Tool (IRAT) currently ranks two LPAI versions (see Updating the CDC's IRAT (Influenza Risk Assessment Tool) Rankings) at the top of their list of viruses with the greatest pandemic potential. An evaluation of the newer HPAI version has yet to be posted.
The upshot of all of this is we don't face just one, two, or even three different H7N9 threats, but rather a growing array of related H7N9 viruses all following their own evolutionary path. A few will thrive, while many will fail, but their numbers can only serve to increase the threat.
Hualan Chen is one of the world's most respected virologists, director of China's National Avian Influenza Reference Laboratory, and is the lead author of today's study which warns of `alarming mutations' they see occurring across this family of H7N9 viruses in China.
Mutations that can not only change LPAI H7N9 viruses into highly pathogenic ones, but that can also potentially make them a greater human pandemic threat.
The open access study is a bit technical, and I've only included a few excerpts (bolding mine) , but it is well worth reading in its entirety.

H7N9 virulent mutants detected in chickens in China pose an increased threat to humans
Open

Jianzhong Shi1,*, Guohua Deng1,*, Huihui Kong1,*, Chunyang Gu1,*, Shujie Ma1,*, Xin Yin1,*, Xianying Zeng1, Pengfei Cui1, Yan Chen1, Huanliang Yang1, Xiaopeng Wan1, Xiurong Wang1, Liling Liu1, Pucheng Chen1, Yongping Jiang1, Jinxiong Liu1, Yuntao Guan1, Yasuo Suzuki2, Mei Li1, Zhiyuan Qu1, Lizheng Guan1, Jinkai Zang1, Wenli Gu1, Shuyu Han1, Yangming Song1, Yuzhen Hu1, Zeng Wang1, Linlin Gu1, Wenyu Yang1, Libin Liang1, Hongmei Bao1, Guobin Tian1, Yanbing Li1, Chuanling Qiao1, Li Jiang1, Chengjun Li1, Zhigao Bu1 and Hualan Chen1
Correspondence: Hualan Chen, E-mail: chenhualan@caas.cn
*These six authors contributed equally to this work

Received 11 July 2017; Revised 17 September 2017; Accepted 26 September 2017
Advance online publication 24 October 2017

Abstract

Certain low pathogenic avian influenza viruses can mutate to highly pathogenic viruses when they circulate in domestic poultry, at which point they can cause devastating poultry diseases and severe economic damage. The H7N9 influenza viruses that emerged in 2013 in China had caused severe human infections and deaths. However, these viruses were nonlethal in poultry. It is unknown whether the H7N9 viruses can acquire additional mutations during their circulation in nature and become lethal to poultry and more dangerous for humans.
Here, we evaluated the evolution of H7N9 viruses isolated from avian species between 2013 and 2017 in China and found 23 different genotypes, 7 of which were detected only in ducks and were genetically distinct from the other 16 genotypes that evolved from the 2013 H7N9 viruses.
Importantly, some H7N9 viruses obtained an insertion of four amino acids in their hemagglutinin (HA) cleavage site and were lethal in chickens. The index strain was not lethal in mice or ferrets, but readily obtained the 627K or 701N mutation in its PB2 segment upon replication in ferrets, causing it to become highly lethal in mice and ferrets and to be transmitted efficiently in ferrets by respiratory droplet.
H7N9 viruses bearing the HA insertion and PB2 627K mutation have been detected in humans in China. Our study indicates that the new H7N9 mutants are lethal to chickens and pose an increased threat to human health, and thus highlights the need to control and eradicate the H7N9 viruses to prevent a possible pandemic.

(SNIP)

Discussion

Influenza viruses mutate; it is their nature. The most undesirable mutations are the ones that convert a low pathogenic avian influenza virus to a highly pathogenic avian influenza virus and the ones that allow a new influenza virus to be transmissible in humans. In this study, we show that these alarming mutations are occurring in the H7N9 viruses.

Our findings provide important information for the control of H7N9 influenza. As soon as we detected the highly pathogenic H7N9 mutants in chickens, a series of actions were taken to prevent and minimize the damage they could cause to both poultry and humans, including the establishment of a rapid differential diagnostic test45, urgent surveillance in poultry, careful analysis of samples from human patients, and evaluation of a poultry vaccine.

(Continue . . . )


None of this means that H7N9 will be ready for prime time this winter, but it is no secret that the scientific community is growing increasingly worried over the direction these viruses are taking.

Stay tuned.


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