Wednesday, May 16, 2018

Emerg. Infect. & Microbes: Novel Triple-Reassortant influenza Viruses In Pigs, Guangxi, China


As pork production rises around the world - particularly in countries where there is poor biosecurity and little surveillance - the risks of seeing another novel swine flu virus emerge as a pandemic threat continues to grow. 
While we watch avian H5 & H7 flu viruses with particular concern - mainly due to their high mortality rates in humans - swine, or swine-avian-human triple reassortant viruses - are perhaps even more likely to emerge as a pandemic threat.
Two and a half years ago, Chen Hualan - director of China's National Avian Influenza Reference Laboratory - gave an interview to Xinhua where she pegged the EA (Eurasian Avian-like) H1N1 swine virus (EAH1N1) as having perhaps the greatest pandemic potential of any of the novel viruses in circulation.

Avian-like H1N1 swine flu may "pose highest pandemic threat": study

WASHINGTON, Dec. 28 (Xinhua) -- The Eurasian avian-like H1N1 (EAH1N1) swine flu viruses, which have circulated in pigs since 1979, have obtained the ability to infect humans and may "pose the highest pandemic threat" among the flu viruses currently circulating in animals, Chinese researchers said Monday.
"Pigs are considered important intermediate hosts for flu viruses," Chen Hualan, director of China's National Avian Influenza Reference Laboratory, who led the study, said in an written interview with Xinhua.

"Based on scientific analysis and comprehensive comparison of the main animal flu viruses: H1N1, H3N2, H5N1, H7N9, H9N2 and EAH1N1, we found the EAH1N1 is the one most likely to cause next human flu pandemic. We should attach great importance to the EAH1N1."
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And indeed, we've been following the evolution of EAH1N1, along with other novel swine-origin viruses in China, with considerable interest.  A few recent blogs include:
Emerg. Microbes & Infect.: Effect Of D701N Substitution In PB2 Of EAH1N1 Swine Flu Viruses
J. Virology: A Single Amino Acid Change Alters Transmissability Of EAH1N1 In Guinea Pigs
Emerg. Microbes & Inf.: Pathogenicity & Transmission Of A Swine Influenza A(H6N6) Virus - China
Lest anyone think this is strictly a Chinese problem, we've also spent considerable time looking at the evolution and emergence of North American, European, and South American swine flu viruses as well.  Regions not mentioned are likely to have little or no surveillance and reporting.
I&ORV: Triple-Reassortant Novel H3 Virus of Human/Swine Origin Established In Danish Pigs
EID Journal: Characterization of a Novel Human Influenza A(H1N2) Virus Variant, Brazil

MMWR: Investigation Into H3N2v Outbreak In Ohio & Michigan - Summer 2016
J. Virol: Novel Reassortant Human-like H3N2 & H3N1 Influenza A Viruses In Pigs
And as we discussed yesterday (see PNAS: Broad Receptor Engagement of PDCoV May Potentiate Its Cross-Species Transmissibility), influenza isn't the only zoonotic disease concern when it comes to pigs.

Nature's Scientific Reports carries two related studies (albeit by different authors) on influenza in China's commercial swine production industry.  The first, which is linked below with a short quote, is an article on surveillance.
Prospective surveillance for influenza. virus in Chinese swine farms
Benjamin D. Anderson, Mai-Juan Ma, Guo-Lin Wang, Zhen-Qiang Bi, Bing Lu, Xian-Jun Wang, Chuang-Xin Wang, Shan-Hui Chen, Yan-Hua Qian, Shao-Xia Song, Min Li, Teng Zhao, Meng-Na Wu, Laura K. Borkenhagen, Wu-Chun Cao & Gregory C. Gray
Overall, these first year data suggest that IAV is quite ubiquitous in the swine production environment and demonstrate an association between the different types of environmental sampling used. Given the mounting evidence that some of these viruses freely move between pigs and swine workers, and that mixing of these viruses can yield progeny viruses with pandemic potential, it seems imperative that routine surveillance for novel IAVs be conducted in commercial swine farms.

The second study (below) tells us a lot more about the growing number of novel triple reassortant swine-origin flu viruses circulating in Guangxi, China over the past few years.

Out of 15 isolates selected, researchers found 10 novel reassortant viruses (see chart below), all hybrids of EAH1N1, H1N1/09, CS H1N1, and HL H3N2, and all reportedly replicated in mice without adaptation, with several proving to be lethal.

Being a snapshot in time, and taken from a single Chinese province (ranked 11th in population), this likely only reveals a fraction of the viral diversity on Chinese pig farms.

I've only posted the link, abstract, and as short excerpt from the discussion. Follow the link below to read it in its entirety.

Novel triple-reassortant influenza viruses in pigs, Guangxi, China 
Ping He, Guojun Wang, Yanning Mo, Qingxiong Yu, Xiong Xiao, Wenjuan Yang,
Weifeng Zhao, Xuan Guo, Qiong Chen, Jianqiao He, Mingli Liang, Jian Zhu, Yangbao Ding, Zuzhang Wei, Kang Ouyang, Fang Liu, Hui Jian, Weijian Huang,
Adolfo GarcĂ­a-Sastre & Ying Chen

Emerging Microbes & Infections volume 7, Article number: 85 (2018)

Published:16 May 2018
Considered a “mixing vessel” for influenza viruses, pigs can give rise to new influenza virus reassortants that can threaten humans. During our surveillance of pigs in Guangxi, China from 2013 to 2015, we isolated 11 H1N1 and three H3N2 influenza A viruses of swine origin (IAVs-S). 
Out of the 14, we detected ten novel triple-reassortant viruses, which contained surface genes (hemagglutinin and neuraminidase) from Eurasian avian-like (EA) H1N1 or seasonal human-like H3N2, matrix (M) genes from H1N1/2009 pandemic or EA H1N1, nonstructural (NS) genes from classical swine, and the remaining genes from H1N1/2009 pandemic. 

Mouse studies indicate that these IAVs-S replicate efficiently without prior adaptation, with some isolates demonstrating lethality. Notably, the reassortant EA H1N1 viruses with EA-like M gene have been reported in human infections. Further investigations will help to assess the potential risk of these novel triple-reassortant viruses to humans.
Currently, influenza A H1N1 and H3N2 viruses are the circulating seasonal influenza A viruses subtypes in human. The H1N1/2009 pandemic became the current seasonal H1N1 virus.
Our EA H1N1 HAs share < 73.7 and 78.1% similarity with the H1N1/2009 pandemic vaccine strain (A/Michigan/45/2015 H1N1), at nucleotide level and amino acid level, respectively. Our H3N2 IAVs-S share < 94.1 and 91.5% similarity with the H3N2 vaccine strain (A/Hong Kong/4801/2014 H3N2), at nucleotide level and amino acid level, respectively.
Studies have reported that seasonal trivalent inactivated influenza vaccine induce poor cross-reactive antibodies to EA H1N1 virus23 and does not protect against swine H3N257. Importantly, according to the risk assessment tool, which is developed by the Centers for Disease Control and Prevention in the United States to evaluate the pandemic potential of different influenza strains58, we found that the EA H1N1 and swine H3N2 viruses are among the animal viruses with the highest risk score in Yang’s analysis26. Besides, at least one human infection with a similar reassortant IAV-S has been reported22.
We suggest that intensive surveillance of IAV-S and of swine-to-human infections with the IAV-S described in our study should be a priority for future research.
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