#Origins of the 1918 #Pandemic: Revisiting the #Swine “Mixing Vessel” #Hypothesis (Am J Epidemiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Am J Epidemiol. 2018 Dec 1;187(12):2498-2502. doi: 10.1093/aje/kwy150.

Origins of the 1918 Pandemic: Revisiting the Swine “Mixing Vessel” Hypothesis.

Nelson MI1, Worobey M2.

Author information: 1 Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland. 2 Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, Arizona.

 

Abstract

How influenza A viruses host-jump from animal reservoir species to humans, which can initiate global pandemics, is a central question in pathogen evolution. The zoonotic and spatial origins of the influenza virus associated with the “Spanish flu” pandemic of 1918 have been debated for decades. Outbreaks of respiratory disease in US swine occurred concurrently with disease in humans, raising the possibility that the 1918 virus originated in pigs. Swine also were proposed as “mixing vessel” intermediary hosts between birds and humans during the 1957 Asian and 1968 Hong Kong pandemics. Swine have presented an attractive explanation for how avian viruses overcome the substantial evolutionary barriers presented by different cellular environments in humans and birds. However, key assumptions underpinning the swine mixing-vessel model of pandemic emergence have been challenged in light of new evidence. Increased surveillance in swine has revealed that human-to-swine transmission actually occurs far more frequently than the reverse, and there is no empirical evidence that swine played a role in the emergence of human influenza in 1918, 1957, or 1968. Swine-to-human transmission occurs periodically and can trigger pandemics, as in 2009. But swine are not necessary to mediate the establishment of avian viruses in humans, which invites new perspectives on the evolutionary processes underlying pandemic emergence.

PMID: 30508193 DOI: 10.1093/aje/kwy150

Keywords: Avian Influenza; Swine Influenza; Influenza A; Pandemic Influenza; H1N1; Spanish Flu; Pigs; Reassortant strain.

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#Tissue #tropisms opt for transmissible #reassortants during #avian and #swine #influenza A virus co-infection in swine (PLoS Pathogens, abstract)

[Source: PLoS Pathogens, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Tissue tropisms opt for transmissible reassortants during avian and swine influenza A virus co-infection in swine

Xiaojian Zhang , Hailiang Sun , Fred L. Cunningham , Lei Li , Katie Hanson-Dorr, Matthew W. Hopken, Jim Cooley, Li-Ping Long, John A. Baroch, Tao Li, Brandon S. Schmit, Xiaoxu Lin, Alicia K. Olivier,  [ … ], Xiu-Feng Wan

Published: December 3, 2018 / DOI: https://doi.org/10.1371/journal.ppat.1007417 / This is an uncorrected proof.

 

Abstract

Genetic reassortment between influenza A viruses (IAVs) facilitate emergence of pandemic strains, and swine are proposed as a “mixing vessel” for generating reassortants of avian and mammalian IAVs that could be of risk to mammals, including humans. However, how a transmissible reassortant emerges in swine are not well understood. Genomic analyses of 571 isolates recovered from nasal wash samples and respiratory tract tissues of a group of co-housed pigs (influenza-seronegative, avian H1N1 IAV–infected, and swine H3N2 IAV–infected pigs) identified 30 distinct genotypes of reassortants. Viruses recovered from lower respiratory tract tissues had the largest genomic diversity, and those recovered from turbinates and nasal wash fluids had the least. Reassortants from lower respiratory tracts had the largest variations in growth kinetics in respiratory tract epithelial cells, and the cold temperature in swine nasal cells seemed to select the type of reassortant viruses shed by the pigs. One reassortant in nasal wash samples was consistently identified in upper, middle, and lower respiratory tract tissues, and it was confirmed to be transmitted efficiently between pigs. Study findings suggest that, during mixed infections of avian and swine IAVs, genetic reassortments are likely to occur in the lower respiratory track, and tissue tropism is an important factor selecting for a transmissible reassortant.

 

Author summary

Genetic reassortments between avian and swine influenza viruses are likely to occur in the swine lower respiratory track, and tissue tropism is an important factor selecting for a transmissible reassortant; determination of tissue tropisms for potential reassortants between contemporary avian and swine influenza viruses would help identify transmissible reassortants with public health risks.

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Citation: Zhang X, Sun H, Cunningham FL, Li L, Hanson-Dorr K, Hopken MW, et al. (2018) Tissue tropisms opt for transmissible reassortants during avian and swine influenza A virus co-infection in swine. PLoS Pathog 14(12): e1007417. https://doi.org/10.1371/journal.ppat.1007417

Editor: Anice C. Lowen, Emory University School of Medicine, UNITED STATES

Received: July 24, 2018; Accepted: October 18, 2018; Published: December 3, 2018

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: The sequence of A/swine/Texas/A01104013/2012 (H3N2) and A/mallard/Wisconsin/A00751454/2009 (H1N1) viruses are available from Genbank under the accession numbers JX280447 to JX280454 and MH879773 to MH879780. All other relevant data are included in the main text of this paper or the Supporting Information files associated with this paper.

Funding: This study was supported by the U.S. Department of Agriculture and the National Institutes of Health (NIH) [grant number R21AI135820]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Avian Influenza; Swine Influenza; Influenza A; H1N1; H3N2 Pigs; Reassortant strain.

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#Evidence of a fixed internal gene #constellation in #influenza A viruses isolated from #wildbirds in #Argentina (2006-2016) (Emerg Microbes Infect., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Emerg Microbes Infect. 2018 Nov 28;7(1):194. doi: 10.1038/s41426-018-0190-2.

Evidence of a fixed internal gene constellation in influenza A viruses isolated from wild birds in Argentina (2006-2016).

Rimondi A1, Gonzalez-Reiche AS2,3, Olivera VS4, Decarre J5, Castresana GJ6, Romano M7, Nelson MI8, van Bakel H3, Pereda AJ4,9, Ferreri L2, Geiger G2, Perez DR2.

Author information: 1 Instituto de Virologia CICVyA – Instituto Nacional de Tecnología Agropecuaria (INTA), CC25 (1712), Castelar, Buenos Aires, Argentina. rimondi.agustina@inta.gob.ar. 2 Poultry Diagnostic and Research Center, College of Veterinary Medicine, University of Georgia, 953 College Station Rd, Athens, GA, 30602, USA. 3 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. 4 Instituto de Virologia CICVyA – Instituto Nacional de Tecnología Agropecuaria (INTA), CC25 (1712), Castelar, Buenos Aires, Argentina. 5 Instituto de Recursos Biológicos CIRN – Instituto Nacional de Tecnología Agropecuaria (INTA), CC25 (1712), Castelar, Buenos Aires, Argentina. 6 Dirección de Áreas Naturales Protegidas, Organismo Provincial para el Desarrollo Sostenible (O.P.D.S), Gobierno de la provincia de Buenos Aires, General Conesa, Buenos Aires, Argentina. 7 Centro de Investigaciones en Biodiversidad y Ambiente, Rosario (ECOSUR), Rosario, Santa Fe, Argentina. 8 Fogarty International Center, National Institutes of Health, Bethesda, MD, 20894, USA. 9 Instituto de Patobiología CICVyA – Instituto Nacional de Tecnología Agropecuaria (INTA), CC25 (1712), Castelar, Buenos Aires, Argentina.

 

Abstract

Wild aquatic birds are the major reservoir of influenza A virus. Cloacal swabs and feces samples (n = 6595) were collected from 62 bird species in Argentina from 2006 to 2016 and screened for influenza A virus. Full genome sequencing of 15 influenza isolates from 6 waterfowl species revealed subtypes combinations that were previously described in South America (H1N1, H4N2, H4N6 (n = 3), H5N3, H6N2 (n = 4), and H10N7 (n = 2)), and new ones not previously identified in the region (H4N8, H7N7 and H7N9). Notably, the internal gene segments of all 15 Argentine isolates belonged to the South American lineage, showing a divergent evolution of these viruses in the Southern Hemisphere. Time-scaled phylogenies indicated that South American gene segments diverged between ~ 30 and ~ 140 years ago from the most closely related influenza lineages, which include the avian North American (PB1, HA, NA, MP, and NS-B) and Eurasian lineage (PB2), and the equine H3N8 lineage (PA, NP, and NS-A). Phylogenetic analyses of the hemagglutinin and neuraminidase gene segments of the H4, H6, and N8 subtypes revealed recent introductions and reassortment between viruses from the Northern and Southern Hemispheres in the Americas. Remarkably and despite evidence of recent hemagglutinin and neuraminidase subtype introductions, the phylogenetic composition of internal gene constellation of these influenza A viruses has remained unchanged. Considering the extended time and the number of sampled species of the current study, and the paucity of previously available data, our results contribute to a better understanding of the ecology and evolution of influenza virus in South America.

PMID: 30482896 DOI: 10.1038/s41426-018-0190-2

Keywords: Avian Influenza; Reassortant Strains; H1; H3; H4; H5; H7; H8; H10; Argentina; Wild birds.

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Molecular #evolutionary and #antigenic characteristics of newly isolated #H9N2 #avian #influenza viruses in #Guangdong province, #China (Arch Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Arch Virol. 2018 Nov 24. doi: 10.1007/s00705-018-4103-4. [Epub ahead of print]

Molecular evolutionary and antigenic characteristics of newly isolated H9N2 avian influenza viruses in Guangdong province, China.

Zhang J1, Wu H1, Zhang Y1, Cao M1, Brisse M2, Zhu W1,2, Li R1, Liu M1, Cai M3, Chen J4, Chen J5.

Author information: 1 School of Life Science and Engineering, Foshan University, Foshan, 528000, Guangdong, People’s Republic of China. 2 College of Veterinary Medicine, University of Minnesota, Twin Cites Campus, Saint Paul, MN, 55108, USA. 3 Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Xinzao Town, Panyu, Guangzhou, 511436, Guangdong, People’s Republic of China. 4 School of Life Science and Engineering, Foshan University, Foshan, 528000, Guangdong, People’s Republic of China. jianhongchen2012@126.com. 5 School of Life Science and Engineering, Foshan University, Foshan, 528000, Guangdong, People’s Republic of China. jidangchen@fosu.edu.cn.

 

Abstract

Four new H9N2 avian influenza viruses (AIVs) were isolated from domestic birds in Guangdong between December 2015 and April 2016. Nucleotide sequence comparisons indicated that most of the internal genes of these four strains were highly similar to those of human H7N9 viruses. Amino acid substitutions and deletions found in the HA and NA proteins indicated that all four of these new isolates may have an enhanced ability to infect humans and other mammals. A cross-hemagglutinin-inhibition assay, conducted with two vaccine strains that are broadly used in China, suggested that antisera against vaccine candidates could not provide complete inhibition of the new isolates.

PMID: 30474753 DOI: 10.1007/s00705-018-4103-4

Keywords: A/H9N2; Avian Influenza; Reassortant Strains; Poultry; Guangdong; China.

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#Genetic characteristics of #hemagglutinin and #neuraminidase of #avian #influenza A (#H7N9) virus in #Guizhou province, 2014-2017 (Zhonghua Liu Xing Bing Xue Za Zhi, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Zhonghua Liu Xing Bing Xue Za Zhi. 2018 Nov 10;39(11):1465-1471. doi: 10.3760/cma.j.issn.0254-6450.2018.11.009.

[Genetic characteristics of hemagglutinin and neuraminidase of avian influenza A (H7N9) virus in Guizhou province, 2014-2017].

[Article in Chinese; Abstract available in Chinese from the publisher]

Wan YH1, Zhuang L, Zheng QN, Ren LJ, Fu L, Jiang WJ, Tang GP, Zhang DZ, Li SJ.

Author information: 1 Guizhou Provincial Center for Disease Control and Prevention, Guiyang 550004, China.

 

Abstract in English, Chinese

Objective:

To understand the molecular characteristics of hemagglutinin (HA) and neuraminidase (NA) as well as the disease risk of influenza virus A H7N9 in Guizhou province.

Methods:

RNAs were extracted and sequenced from HA and NA genes of H7N9 virus strains obtained from 18 cases of human infection with H7N9 virus and 6 environmental swabs in Guizhou province during 2014-2017. Then the variation and the genetic evolution of the virus were analyzed by using a series of bioinformatics software package.

Results:

Homology analysis of HA and NA genes revealed that 2 strains detected during 2014-2015 shared 98.8%-99.2% and 99.2% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Two strains detected in 2016 and 14 strains detected in 2017 shared 98.2%-99.3% and 97.6%-98.8% similarities with vaccine strain A/Hunan/02650/2016, respectively. Other 6 stains detected in 2017 shared 99.1%-99.4% and 98.9%-99.3% similarities with strain A/Guangdong/17SF003/2016, respectively. Phylogenetic analysis showed that all the strains were directly evolved in the Yangtze River Delta evolution branch, but they were derived from different small branch. PEVPKRKRTAR↓GLF was found in 6 of 24 strains cleavage site sequences of HA protein, indicating the characteristic of highly pathogenic avian influenza virus. Mutations A134V, G186V and Q226L at the receptor binding sites were found in the HA. All the strains had a stalk deletion of 5 amino acid residue “QISNT” in NA protein, and drug resistance mutation R294K occurred in strain A/Guizhou-Danzhai/18980/2017. In addition, potential glycosylation motifs mutations NCS42NCT were found in the NA of 9 of 24 strains.

Conclusions:

HA and NA genes of avian influenza A (H7N9) virus showed genetic divergence in Guizhou province during 2014-2017. The mutations of key sites might enhance the virulence of the virus, human beings are more susceptible to it. Hence, the risk of infection is increasing.

KEYWORDS: Avian influenza A (H7N9) virus; Hemagglutinin gene; Molecular characteristic; Neuraminidase gene

PMID:  30462955

Keywords: Avian Influenza; H7N9; Human; China; Guizhou; Antivirals; Drugs Resistance; Oseltamivir; Reassortant strain.

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#Genetic #compatibility of #reassortants between #avian #H5N1 and #H9N2 #influenza viruses with higher pathogenicity in #mammals (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Genetic compatibility of reassortants between avian H5N1 and H9N2 influenza viruses with higher pathogenicity in mammals

Yasuha Arai, Madiha S. Ibrahim, Emad M. Elgendy, Tomo Daidoji, Takao Ono, Yasuo Suzuki, Takaaki Nakaya, Kazuhiko Matsumoto, Yohei Watanabe

DOI: 10.1128/JVI.01969-18

 

ABSTRACT

The co-circulation of H5N1 and H9N2 avian influenza viruses in birds in Egypt provides reassortment opportunities between these two viruses. However, little is known about the emergence potential of reassortants derived from Egyptian H5N1 and H9N2 viruses and about the biological properties of such reassortants. To evaluate the potential public health risk of reassortants of these viruses, we used reverse genetics to generate the 63 possible reassortants derived from contemporary Egyptian H5N1 and H9N2 viruses, containing the H5N1 surface gene segments and combinations of the H5N1 and H9N2 internal gene segments, and analyzed their genetic compatibility, replication ability and virulence in mice. Genes in the reassortants showed remarkably high compatibility. Replication of most reassortants was higher than the parental H5N1 virus in human cells. Six reassortants were thought to emerge in birds under neutral or positive selective pressure, and four of them had higher pathogenicity in vivo than the parental H5N1 and H9N2 viruses. Our results indicated that H5N1-H9N2 reassortants could be transmitted efficiently to mammals with significant public health risk if they emerge in Egypt, although the viruses might not emerge frequently in birds.

 

IMPORTANCE

Close interaction between avian influenza (AI) viruses and humans in Egypt appears to have resulted in many of the worldwide cases of human infections by both H5N1 and H9N2 AI viruses. Egypt is regarded as a hot spot of AI virus evolution. Although no natural reassortant of H5N1 and H9N2 AI viruses has been reported so far, their co-circulation in Egypt may allow emergence of reassortants that may present a significant public health risk. Using reverse genetics, we report here the first comprehensive data showing that H5N1-N9N2 reassortants have fairly high genetic compatibility and possibly higher pathogenicity in mammals, including humans, than the parental viruses. Our results provide insight into the emergence potential of avian H5N1-H9N2 reassortants that may pose a high public health risk.

Copyright © 2018 Arai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Avian Influenza; H5N1; H9N2; Reassortant strains.

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High frequency of #reassortment after #coinfection of #chickens with the #H4N6 and #H9N2 #influenza A viruses and the biological characteristics of the reassortants (Vet Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vet Microbiol. 2018 Aug;222:11-17. doi: 10.1016/j.vetmic.2018.06.011. Epub 2018 Jun 18.

High frequency of reassortment after co-infection of chickens with the H4N6 and H9N2 influenza A viruses and the biological characteristics of the reassortants.

Li X1, Liu B2, Ma S3, Cui P3, Liu W4, Li Y4, Guo J5, Chen H6.

Author information: 1 College of Agricultural, Liaocheng University, Liaocheng, People’s Republic of China. Electronic address: lixuyong@lcu.edu.cn. 2 College of veterinary medicine, Qingdao Agricultural University, Qingdao, People’s Republic of China. 3 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, People’s Republic of China. 4 College of Agricultural, Liaocheng University, Liaocheng, People’s Republic of China. 5 College of Agricultural, Liaocheng University, Liaocheng, People’s Republic of China. Electronic address: guojing@lcu.edu.cn. 6 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, People’s Republic of China. Electronic address: chenhualan@caas.cn.

 

Abstract

H4 and H9 avian influenza viruses (AIVs) are two of the most prevalent influenza viruses worldwide. The co-existence of H4 and H9 viruses in multiple avian species provides an opportunity for the generation of novel reassortants and for viral evolution. The diversity of the biological characteristics of the reassortants enhances the potential threat to the poultry industry and to public health. To evaluate the reassortment of these viruses and the potential public risk of the reassortants, we co-infected chickens with H4N6 and H9N2 viruses derived from poultry and tested the replication and virulence of the reassortant viruses in mice. A high frequency of reassortment was detected in chickens after co-infection with these two viruses and nine reassortants of six genotypes were purified from the chicken samples. Two H9N2 reassortants containing the PA of the parent H4N6 virus showed higher virulence than the parent H9N2 virus, revealing the significant role of the H4N6 wt virus PA gene in viral reassortment. Analysis of the polymerase activity of the ribonucleoprotein (RNP) complex in vitro suggested that the PA of H4N6 wt origin enhanced polymerase activity. Our results indicate that co-infection of an avian individual with the H4N6 and H9N2 viruses leads to a high frequency of reassortment and generates some reassortants that have higher virulence than the wild-type viruses in mammals. These results highlight the potential public risk of the avian influenza reassortants and the importance of surveillance of the co-existence of the H4N6 and H9N2 viruses in avian species and other animals.

KEYWORDS: Chicken; Co-infection; H4N6; H9N2; Mice; Reassortants

PMID: 30080665 DOI: 10.1016/j.vetmic.2018.06.011 [Indexed for MEDLINE]

Keywords: Avian Influenza; H4N6; H9N2; Reassortant Strain; Poultry.

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