Evolution and Pathogenesis of Avian and Animal Influenza Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 71533

Special Issue Editors


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Guest Editor
Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, Greifswald, Germany
Interests: genetic basis for adaptation and virulence of avian influenza virus in poultry and mammals; interspecies transmission; virus-host interaction; development and evaluation of vaccines

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Guest Editor
Laboratory for Pathology II Department of Experimental Animal Facilities and Biorisk Management Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut Südufer 10, 17493 Greifswald - Insel Riems, Germany

Special Issue Information

Dear Colleagues,

Emerging and re-emerging influenza viruses pose a continuous threat to animal and human health. We are facing a highly mutable virus seeking adaptation on different hosts and in harsh environmental conditions. Despite extensive research, particularly to detect, identify, and characterize (novel) influenza viruses in different animal species, vigilance is warranted to monitor changes in virus–host ecology that enable efficient adaptation, high virulence, and interspecies transmission. In this Special Issue, we welcome articles, short communications, case reports, reviews, and commentaries on the evolution and pathogenesis of influenza viruses in birds and mammals. The scope of this SI is to gather papers on, but not limited to, genetic and evolutionary analysis, genetic determinants for virulence and adaptation in birds and mammals, assessment of pathogenicity and transmission, virus–host–ecology interaction, macro- and microscopic alterations, tropism to different organs/cells, epidemiological investigation, and development of new laboratory tools for diagnosis and characterization of influenza viruses.

Dr. El-Sayed M Abdelwhab
Dr. Angele Breithaupt
Guest Editors

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Keywords

  • Avian influenza
  • pathogenesis
  • virus evolution
  • zoonotic diseases
  • pandemic
  • tropism
  • animals
  • birds
  • reservoir
  • virulence determinants

Published Papers (18 papers)

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19 pages, 6932 KiB  
Article
Avian Influenza H7N9 Virus Adaptation to Human Hosts
by Swan Tan, Muhammad Farhan Sjaugi, Siew Chinn Fong, Li Chuin Chong, Hadia Syahirah Abd Raman, Nik Elena Nik Mohamed, Joseph Thomas August and Asif M. Khan
Viruses 2021, 13(5), 871; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050871 - 10 May 2021
Cited by 2 | Viewed by 3621
Abstract
Avian influenza virus A (H7N9), after circulating in avian hosts for decades, was identified as a human pathogen in 2013. Herein, amino acid substitutions possibly essential for human adaptation were identified by comparing the 4706 aligned overlapping nonamer position sequences (1–9, 2–10, etc.) [...] Read more.
Avian influenza virus A (H7N9), after circulating in avian hosts for decades, was identified as a human pathogen in 2013. Herein, amino acid substitutions possibly essential for human adaptation were identified by comparing the 4706 aligned overlapping nonamer position sequences (1–9, 2–10, etc.) of the reported 2014 and 2017 avian and human H7N9 datasets. The initial set of virus sequences (as of year 2014) exhibited a total of 109 avian-to-human (A2H) signature amino acid substitutions. Each represented the most prevalent substitution at a given avian virus nonamer position that was selectively adapted as the corresponding index (most prevalent sequence) of the human viruses. The majority of these avian substitutions were long-standing in the evolution of H7N9, and only 17 were first detected in 2013 as possibly essential for the initial human adaptation. Strikingly, continued evolution of the avian H7N9 virus has resulted in avian and human protein sequences that are almost identical. This rapid and continued adaptation of the avian H7N9 virus to the human host, with near identity of the avian and human viruses, is associated with increased human infection and a predicted greater risk of human-to-human transmission. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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20 pages, 4111 KiB  
Article
H7N7 Avian Influenza Virus Mutation from Low to High Pathogenicity on a Layer Chicken Farm in the UK
by Alexander M. P. Byrne, Scott M. Reid, Amanda H. Seekings, Alejandro Núñez, Ana B. Obeso Prieto, Susan Ridout, Caroline J. Warren, Anita Puranik, Vanessa Ceeraz, Stephen Essen, Marek J. Slomka, Jill Banks, Ian H. Brown and Sharon M. Brookes
Viruses 2021, 13(2), 259; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020259 - 08 Feb 2021
Cited by 8 | Viewed by 3172
Abstract
Avian influenza virus (AIV) subtypes H5 and H7 are capable of mutating from low to high pathogenicity strains, causing high mortality in poultry with significant economic losses globally. During 2015, two outbreaks of H7N7 low pathogenicity AIV (LPAIV) in Germany, and one each [...] Read more.
Avian influenza virus (AIV) subtypes H5 and H7 are capable of mutating from low to high pathogenicity strains, causing high mortality in poultry with significant economic losses globally. During 2015, two outbreaks of H7N7 low pathogenicity AIV (LPAIV) in Germany, and one each in the United Kingdom (UK) and The Netherlands occurred, as well as single outbreaks of H7N7 high pathogenicity AIV (HPAIV) in Germany and the UK. Both HPAIV outbreaks were linked to precursor H7N7 LPAIV outbreaks on the same or adjacent premises. Herein, we describe the clinical, epidemiological, and virological investigations for the H7N7 UK HPAIV outbreak on a farm with layer chickens in mixed free-range and caged units. H7N7 HPAIV was identified and isolated from clinical samples, as well as H7N7 LPAIV, which could not be isolated. Using serological and molecular evidence, we postulate how the viruses spread throughout the premises, indicating potential points of incursion and possible locations for the mutation event. Serological and mortality data suggested that the LPAIV infection preceded the HPAIV infection and afforded some clinical protection against the HPAIV. These results document the identification of a LPAIV to HPAIV mutation in nature, providing insights into factors that drive its manifestation during outbreaks. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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11 pages, 1896 KiB  
Article
Genomic Evidence for Sequestration of Influenza A Virus Lineages in Sea Duck Host Species
by Dillon S. McBride, Sarah E. Lauterbach, Yao-Tsun Li, Gavin J. D. Smith, Mary Lea Killian, Jacqueline M. Nolting, Yvonne C. F. Su and Andrew S. Bowman
Viruses 2021, 13(2), 172; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020172 - 24 Jan 2021
Cited by 2 | Viewed by 2405
Abstract
Wild birds are considered the natural reservoir of influenza A viruses (IAVs) making them critical for IAV surveillance efforts. While sea ducks have played a role in novel IAV emergence events that threatened food security and public health, very few surveillance samples have [...] Read more.
Wild birds are considered the natural reservoir of influenza A viruses (IAVs) making them critical for IAV surveillance efforts. While sea ducks have played a role in novel IAV emergence events that threatened food security and public health, very few surveillance samples have been collected from sea duck hosts. From 2014–2018, we conducted surveillance focused in the Mississippi flyway, USA at locations where sea duck harvest has been relatively successful compared to our other sampling locations. Our surveillance yielded 1662 samples from sea ducks, from which we recovered 77 IAV isolates. Our analyses identified persistence of sea duck specific IAV lineages across multiple years. We also recovered sea duck origin IAVs containing an H4 gene highly divergent from the majority of North American H4-HA with clade node age of over 65 years. Identification of IAVs with long branch lengths is indicative of substantial genomic change consistent with persistence without detection by surveillance efforts. Sea ducks play a role in the movement and long-term persistence of IAVs and are likely harboring more undetected IAV diversity. Sea ducks should be a point of emphasis for future North American wild bird IAV surveillance efforts. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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14 pages, 1543 KiB  
Article
Highly Pathogenic Avian Influenza (H5N1) Landscape Suitability Varies by Wetland Habitats and the Degree of Interface between Wild Waterfowl and Poultry in India
by Michael G. Walsh, Siobhan M. Mor and Shah Hossain
Viruses 2020, 12(11), 1290; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111290 - 11 Nov 2020
Cited by 3 | Viewed by 4078
Abstract
Highly pathogenic avian influenza (HPAI) virus, subtype H5N1, constitutes one of the world’s most important health and economic concerns given the catastrophic impact of epizootics on the poultry industry, the high mortality attending spillover in humans, and its potential as a source subtype [...] Read more.
Highly pathogenic avian influenza (HPAI) virus, subtype H5N1, constitutes one of the world’s most important health and economic concerns given the catastrophic impact of epizootics on the poultry industry, the high mortality attending spillover in humans, and its potential as a source subtype for a future pandemic. Nevertheless, we still lack an adequate understanding of HPAI H5N1 epidemiology and infection ecology. The nature of the wild waterfowl–poultry interface, and the sharing of diverse wetland habitat among these birds, currently underscore important knowledge gaps. India has emerged as a global hotspot for HPAI H5N1, while also providing critical wintering habitat for many species of migratory waterfowl and year-round habitat for several resident waterfowl species. The current study sought to examine the extent to which the wild waterfowl–poultry interface, varied wetland habitat, and climate influence HPAI H5N1 epizootics in poultry in India. Using World Organisation for Animal Health reported outbreaks, this study showed that the wild waterfowl–poultry interface and lacustrine, riparian, and coastal marsh wetland systems were strongly associated with landscape suitability, and these relationships varied by scale. Although increasing poultry density was associated with increasing risk, this was only the case in the absence of wild waterfowl habitat, and only at a local scale. In landscapes increasingly shared between wild waterfowl and poultry, suitability was greater among lower density poultry, again at a local scale only. These findings provide further insight into the occurrence of HPAI H5N1 in India and suggest important landscape targets for blocking the waterfowl–poultry interface to interrupt virus transmission and prevent future outbreaks. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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20 pages, 2666 KiB  
Article
Evaluation of the Pathogenicity and the Escape from Vaccine Protection of a New Antigenic Variant Derived from the European Human-Like Reassortant Swine H1N2 Influenza Virus
by Céline Deblanc, Stéphane Quéguiner, Stéphane Gorin, Amélie Chastagner, Séverine Hervé, Frédéric Paboeuf and Gaëlle Simon
Viruses 2020, 12(10), 1155; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101155 - 12 Oct 2020
Cited by 9 | Viewed by 2281
Abstract
The surveillance of swine influenza A viruses in France revealed the emergence of an antigenic variant following deletions and mutations that are fixed in the HA-encoding gene of the European human-like reassortant swine H1N2 lineage. In this study, we compared the outcomes of [...] Read more.
The surveillance of swine influenza A viruses in France revealed the emergence of an antigenic variant following deletions and mutations that are fixed in the HA-encoding gene of the European human-like reassortant swine H1N2 lineage. In this study, we compared the outcomes of the parental (H1huN2) and variant (H1huN2Δ14–147) virus infections in experimentally-inoculated piglets. Moreover, we assessed and compared the protection that was conferred by an inactivated vaccine currently licensed in Europe. Three groups of five unvaccinated or vaccinated piglets were inoculated with H1huN2 or H1huN2Δ14–147 or mock-inoculated, respectively. In unvaccinated piglets, the variant strain induced greater clinical signs than the parental virus, in relation to a higher inflammatory response that involves TNF-α production and a huge afflux of granulocytes into the lung. However, both infections led to similar levels of virus excretion and adaptive (humoral and cellular) immune responses in blood. The vaccinated animals were clinically protected from both infectious challenges and did not exhibit any inflammatory responses, regardless the inoculated virus. However, whereas vaccination prevented virus shedding in H1huN2-infected animals, it did not completely inhibit the multiplication of the variant strain, since live virus particles were detected in nasal secretions that were taken from H1huN2Δ14–147-inoculated vaccinated piglets. This difference in the level of vaccine protection was probably related to the poorer ability of the post-vaccine antibodies to neutralize the variant virus than the parental virus, even though post-vaccine cellular immunity appeared to be equally effective against both viruses. These results suggest that vaccine antigens would potentially need to be updated if this variant becomes established in Europe. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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19 pages, 2736 KiB  
Article
PA from a Recent H9N2 (G1-Like) Avian Influenza A Virus (AIV) Strain Carrying Lysine 367 Confers Altered Replication Efficiency and Pathogenicity to Contemporaneous H5N1 in Mammalian Systems
by Ahmed Mostafa, Sara H. Mahmoud, Mahmoud Shehata, Christin Müller, Ahmed Kandeil, Rabeh El-Shesheny, Hanaa Z. Nooh, Ghazi Kayali, Mohamed A. Ali and Stephan Pleschka
Viruses 2020, 12(9), 1046; https://0-doi-org.brum.beds.ac.uk/10.3390/v12091046 - 20 Sep 2020
Cited by 12 | Viewed by 3647
Abstract
Egypt is a hotspot for H5- and H9-subtype avian influenza A virus (AIV) infections and co-infections in poultry by both subtypes have been frequently reported. However, natural genetic reassortment of these subtypes has not been reported yet. Here, we evaluated the genetic compatibility [...] Read more.
Egypt is a hotspot for H5- and H9-subtype avian influenza A virus (AIV) infections and co-infections in poultry by both subtypes have been frequently reported. However, natural genetic reassortment of these subtypes has not been reported yet. Here, we evaluated the genetic compatibility and replication efficiency of reassortants between recent isolates of an Egyptian H5N1 and a H9N2 AIV (H5N1EGY and H9N2EGY). All internal viral proteins-encoding segments of the contemporaneous G1-like H9N2EGY, expressed individually and in combination in the genetic background of H5N1EGY, were genetically compatible with the other H5N1EGY segments. At 37 °C the replication efficiencies of H5N1EGY reassortants expressing the H9N2EGY polymerase subunits PB2 and PA (H5N1PB2-H9N2EGY, H5N1PA-H9N2EGY) were higher than the wild-type H5N1EGY in Madin-Darby canine kidney (MDCK-II) cells. This could not be correlated to viral polymerase activity as this was found to be improved for H5N1PB2-H9N2EGY, but reduced for H5N1PA-H9N2EGY. At 33 °C and 39 °C, H5N1PB2-H9N2EGY and H5N1PA-H9N2EGY replicated to higher levels than the wild-type H5N1EGY in human Calu-3 and A549 cell lines. Nevertheless, in BALB/c mice both reassortants caused reduced mortality compared to the wild-type H5N1EGY. Genetic analysis of the polymerase-encoding segments revealed that the PAH9N2EGY and PB2H9N2EGY encode for a distinct uncharacterized mammalian-like variation (367K) and a well-known mammalian signature (591K), respectively. Introducing the single substitution 367K into the PA of H5N1EGY enabled the mutant virus H5N1PA-R367K to replicate more efficiently at 37 °C in primary human bronchial epithelial (NHBE) cells and also in A549 and Calu-3 cells at 33 °C and 39 °C. Furthermore, H5N1PA-R367K caused higher mortality in BALB/c mice. These findings demonstrate that H5N1 (Clade 2.2.1.2) reassortants carrying internal proteins-encoding segments of G1-like H9N2 viruses can emerge and may gain improved replication fitness. Thereby such H5N1/H9N2 reassortants could augment the zoonotic potential of H5N1 viruses, especially by acquiring unique mammalian-like aa signatures. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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18 pages, 2205 KiB  
Article
Infection Dynamics of Swine Influenza Virus in a Danish Pig Herd Reveals Recurrent Infections with Different Variants of the H1N2 Swine Influenza A Virus Subtype
by Tarka Raj Bhatta, Pia Ryt-Hansen, Jens Peter Nielsen, Lars Erik Larsen, Inge Larsen, Anthony Chamings, Nicole B. Goecke and Soren Alexandersen
Viruses 2020, 12(9), 1013; https://0-doi-org.brum.beds.ac.uk/10.3390/v12091013 - 10 Sep 2020
Cited by 6 | Viewed by 4017
Abstract
Influenza A virus (IAV) in swine, so-called swine influenza A virus (swIAV), causes respiratory illness in pigs around the globe. In Danish pig herds, a H1N2 subtype named H1N2dk is one of the main circulating swIAV. In this cohort study, the infection dynamic [...] Read more.
Influenza A virus (IAV) in swine, so-called swine influenza A virus (swIAV), causes respiratory illness in pigs around the globe. In Danish pig herds, a H1N2 subtype named H1N2dk is one of the main circulating swIAV. In this cohort study, the infection dynamic of swIAV was evaluated in a Danish pig herd by sampling and PCR testing of pigs from two weeks of age until slaughter at 22 weeks of age. In addition, next generation sequencing (NGS) was used to identify and characterize the complete genome of swIAV circulating in the herd, and to examine the antigenic variability in the antigenic sites of the virus hemagglutinin (HA) and neuraminidase (NA) proteins. Overall, 76.6% of the pigs became PCR positive for swIAV during the study, with the highest prevalence at four weeks of age. Detailed analysis of the virus sequences obtained showed that the majority of mutations occurred at antigenic sites in the HA and NA proteins of the virus. At least two different H1N2 variants were found to be circulating in the herd; one H1N2 variant was circulating at the sow and nursery sites, while another H1N2 variant was circulating at the finisher site. Furthermore, it was demonstrated that individual pigs had recurrent swIAV infections with the two different H1N2 variants, but re-infection with the same H1N2 variant was also observed. Better understandings of the epidemiology, genetic and antigenic diversity of swIAV may help to design better health interventions for the prevention and control of swIAV infections in the herds. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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27 pages, 4059 KiB  
Article
The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model
by Amanda H. Seekings, Wendy A. Howard, Alejandro Nuñéz, Marek J. Slomka, Ashley C. Banyard, Daniel Hicks, Richard J. Ellis, Javier Nuñéz-García, Lorian C. Hartgroves, Wendy S. Barclay, Jill Banks and Ian H. Brown
Viruses 2020, 12(9), 920; https://0-doi-org.brum.beds.ac.uk/10.3390/v12090920 - 21 Aug 2020
Cited by 10 | Viewed by 4049
Abstract
Outbreaks of highly pathogenic avian influenza virus (HPAIV) often result in the infection of millions of poultry, causing up to 100% mortality. HPAIV has been shown to emerge from low pathogenicity avian influenza virus (LPAIV) in field outbreaks. Direct evidence for the emergence [...] Read more.
Outbreaks of highly pathogenic avian influenza virus (HPAIV) often result in the infection of millions of poultry, causing up to 100% mortality. HPAIV has been shown to emerge from low pathogenicity avian influenza virus (LPAIV) in field outbreaks. Direct evidence for the emergence of H7N7 HPAIV from a LPAIV precursor with a rare di-basic cleavage site (DBCS) was identified in the UK in 2008. The DBCS contained an additional basic amino acid compared to commonly circulating LPAIVs that harbor a single-basic amino acid at the cleavage site (SBCS). Using reverse genetics, outbreak HPAIVs were rescued with a DBCS (H7N7DB), as seen in the LPAIV precursor or an SBCS representative of common H7 LPAIVs (H7N7SB). Passage of H7N7DB in chicken embryo tissues showed spontaneous evolution to a HPAIV. In contrast, deep sequencing of extracts from embryo tissues in which H7N7SB was serially passaged showed retention of the LPAIV genotype. Thus, in chicken embryos, an H7N7 virus containing a DBCS appears naturally unstable, enabling rapid evolution to HPAIV. Evaluation in embryo tissue presents a useful approach to study AIV evolution and allows a laboratory-based dissection of molecular mechanisms behind the emergence of HPAIV. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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16 pages, 3501 KiB  
Article
Replication of a Dog-Origin H6N1 Influenza Virus in Cell Culture and Mice
by Shou-Kuan Tsai, Cheng-Hsin Shih, Hui-Wen Chang, Kuang-Huan Teng, Wei-En Hsu, Han-Jia Lin, Han-You Lin, Ching-Huei Huang, Hui-Wen Chen and Lih-Chiann Wang
Viruses 2020, 12(7), 704; https://0-doi-org.brum.beds.ac.uk/10.3390/v12070704 - 30 Jun 2020
Cited by 2 | Viewed by 2609
Abstract
The world’s first natural avian-origin H6N1 influenza A virus infection case in dogs was confirmed in Taiwan in 2014. The H6N1 virus in chickens has been endemic in Taiwan since 1972. Whether the dog H6N1 virus has interspecies transmission potential is the key [...] Read more.
The world’s first natural avian-origin H6N1 influenza A virus infection case in dogs was confirmed in Taiwan in 2014. The H6N1 virus in chickens has been endemic in Taiwan since 1972. Whether the dog H6N1 virus has interspecies transmission potential is the key issue we aim to understand. Following one virus passage in embryonated eggs and two further passages in MDCK cells, we obtained two virus derivatives, E01EE (PB1 739E and PB2 627E) and E01GK (PB1 739G and PB2 627K), respectively. The pathogenicity of E01EE and E01GK was investigated using plaque assay, growth dynamic analysis and cell viability quantification in cells from different animal species. The impact of amino acid mutation on PB1 739 and PB2 627 on viral ribonucleoprotein (RNP) activity was also analyzed. Further mouse infection experiments were performed. The results showed that both E01EE and E01GK decreased cell relative viability of canine MDCK cells, human A549 cells and chicken DF1 cells. E01Gk caused greater cellular harm in MDCK and A549 cells and had significantly higher virus titers in all of the cells compared to E01EE. The PB2 627K but not PB1 739G was the critical mutation that influenced the viral RNP activity. Both E01EE and E01GK caused mice pneumonia and considerable virus shedding, especially E01GK. This report verifies PB2 E627K mutation in virulence and spotlights the potential for the dog H6N1 virus to extend interspecies transmission. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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17 pages, 4123 KiB  
Article
Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation
by Dai-Lun Shin, Wei Yang, Ju-Yi Peng, Bevan Sawatsky, Veronika von von Messling, Georg Herrler and Nai-Huei Wu
Viruses 2020, 12(6), 589; https://0-doi-org.brum.beds.ac.uk/10.3390/v12060589 - 28 May 2020
Cited by 12 | Viewed by 3416
Abstract
Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (α2,6-linked sialic acids) and avian IAV (α2,3-linked sialic acids) and therefore is suited for [...] Read more.
Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (α2,6-linked sialic acids) and avian IAV (α2,3-linked sialic acids) and therefore is suited for adaptation of viruses from other species as suggested by the “mixing vessel theory”. Here, we applied well-differentiated swine airway epithelial cells to find out whether efficient infection by avian IAV requires prior adaption. Furthermore, we analyzed the influence of the sialic acid-binding activity and the virus-induced detrimental effects. Surprisingly, an avian IAV H1N1 strain circulating in European poultry and waterfowl shows increased and prolonged viral replication without inducing a strong innate immune response. This virus could infect the lower respiratory tract in our precision cut-lung slice model. Pretreating the cells with poly (I:C) and/or JAK/STAT pathway inhibitors revealed that the interferon-stimulated innate immune response influences the replication of avian IAV in swine airway epitheliums but not that of swine IAV. Further studies indicated that in the infection by IAVs, the binding affinity of sialic acid is not the sole factor affecting the virus infectivity for swine or human airway epithelial cells, whereas it may be crucial in well-differentiated ferret tracheal epithelial cells. Taken together, our results suggest that the role of pigs being the vessel of interspecies transmission should be reconsidered, and the potential of avian H1N1 viruses to infect mammals needs to be characterized in more detail. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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14 pages, 1561 KiB  
Article
Evolution and Pathogenicity of the H1 and H3 Subtypes of Swine Influenza Virus in Mice between 2016 and 2019 in China
by Yuzhong Zhao, Fachao Sun, Li Li, Ting Chen, Shengliang Cao, Guofei Ding, Fangyuan Cong, Jiaqi Liu, Liting Qin, Sidang Liu and Yihong Xiao
Viruses 2020, 12(3), 298; https://0-doi-org.brum.beds.ac.uk/10.3390/v12030298 - 09 Mar 2020
Cited by 7 | Viewed by 3123
Abstract
Pigs are considered a “mixing vessel” that can produce new influenza strains through genetic reassortments, which pose a threat to public health and cause economic losses worldwide. The timely surveillance of the epidemiology of the swine influenza virus is of importance for prophylactic [...] Read more.
Pigs are considered a “mixing vessel” that can produce new influenza strains through genetic reassortments, which pose a threat to public health and cause economic losses worldwide. The timely surveillance of the epidemiology of the swine influenza virus is of importance for prophylactic action. In this study, 15 H1N1, one H1N2, and four H3N2 strains were isolated from a total of 4080 nasal swabs which were collected from 20 pig farms in three provinces in China between 2016 and 2019. All the isolates were clustered into four genotypes. A new genotype represented by the H1N2 strain was found, whose fragments came from the triple reassortant H1N2 lineage, classical swine influenza virus (cs-H1N1) lineage, and 2009 H1N1 pandemic virus lineage. A/Sw/HB/HG394/2018(H1N1), which was clustered into the cs-H1N1 lineage, showed a close relationship with the 1918 pandemic virus. Mutations determining the host range specificity were found in the hemagglutinin of all isolates, which indicated that all the isolates had the potential for interspecies transmission. To examine pathogenicity, eight isolates were inoculated into 6-week-old female BALB/c mice. The isolates replicated differently, producing different viral loadings in the mice; A/Swine/HB/HG394/2018(H1N1) replicated the most efficiently. This suggested that the cs-H1N1 reappeared, and more attention should be given to the new pandemic to pigs. These results indicated that new reassortments between the different strains occurred, which may increase potential risks to human health. Continuing surveillance is imperative to monitor swine influenza A virus evolution. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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13 pages, 2011 KiB  
Article
Detection of a Reassortant H9N2 Avian Influenza Virus with Intercontinental Gene Segments in a Resident Australian Chestnut Teal
by Tarka Raj Bhatta, Anthony Chamings, Jessy Vibin, Marcel Klaassen and Soren Alexandersen
Viruses 2020, 12(1), 88; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010088 - 13 Jan 2020
Cited by 11 | Viewed by 4669
Abstract
The present study reports the genetic characterization of a low-pathogenicity H9N2 avian influenza virus, initially from a pool and subsequently from individual faecal samples collected from Chestnut teals (Anas castanea) in southeastern Australia. Phylogenetic analyses of six full gene segments and [...] Read more.
The present study reports the genetic characterization of a low-pathogenicity H9N2 avian influenza virus, initially from a pool and subsequently from individual faecal samples collected from Chestnut teals (Anas castanea) in southeastern Australia. Phylogenetic analyses of six full gene segments and two partial gene segments obtained from next-generation sequencing showed that this avian influenza virus, A/Chestnut teal/Australia/CT08.18/12952/2018 (H9N2), was a typical, low-pathogenicity, Eurasian aquatic bird lineage H9N2 virus, albeit containing the North American lineage nucleoprotein (NP) gene segment detected previously in Australian wild birds. This is the first report of a H9N2 avian influenza virus in resident wild birds in Australia, and although not in itself a cause of concern, is a clear indication of spillover and likely reassortment of influenza viruses between migratory and resident birds, and an indication that any lineage could potentially be introduced in this way. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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24 pages, 6274 KiB  
Article
Infection of Human Tracheal Epithelial Cells by H5 Avian Influenza Virus Is Regulated by the Acid Stability of Hemagglutinin and the pH of Target Cell Endosomes
by Tomo Daidoji, Junichi Kajikawa, Yasuha Arai, Yohei Watanabe, Ryohei Hirose and Takaaki Nakaya
Viruses 2020, 12(1), 82; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010082 - 09 Jan 2020
Cited by 6 | Viewed by 3865
Abstract
Despite the possible relationships between tracheal infection and concomitant infection of the terminal part of the lower respiratory tract (bronchioles/alveoli), the behavior of avian influenza viruses (AIVs), such as H5N1, in the conducting airways is unclear. To examine the tropism of AIVs for [...] Read more.
Despite the possible relationships between tracheal infection and concomitant infection of the terminal part of the lower respiratory tract (bronchioles/alveoli), the behavior of avian influenza viruses (AIVs), such as H5N1, in the conducting airways is unclear. To examine the tropism of AIVs for cells lining the conducting airways of humans, we established human tracheal epithelial cell clones (HTEpC-Ts) and examined their susceptibility to infection by AIVs. The HTEpC-Ts showed differing susceptibility to H5N1 and non-zoonotic AIVs. Viral receptors expressed by HTEpC-Ts bound all viruses; however, the endosomal pH was associated with the overall susceptibility to infection by AIVs. Moreover, H5N1 hemagglutinin broadened viral tropism to include HTEpC-Ts, because it had a higher pH threshold for viral–cell membrane fusion. Thus, H5N1 viruses infect human tracheal epithelial cells as a result of their higher pH threshold for membrane fusion which may be one mechanism underlying H5N1 pathogenesis in human airway epithelia. Efficient replication of H5N1 in the conducting airways of humans may facilitate infection of the lower respiratory tract. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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13 pages, 3349 KiB  
Article
The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses
by Mengkai Cai, Ruting Zhong, Chenxiao Qin, Zhiqing Yu, Xiaoyan Wen, Junsi Xian, Yongjie Chen, Yu Cai, Heyou Yi, Lang Gong and Guihong Zhang
Viruses 2020, 12(1), 52; https://0-doi-org.brum.beds.ac.uk/10.3390/v12010052 - 02 Jan 2020
Cited by 11 | Viewed by 3087
Abstract
The Eurasian avian-like swine (EA) H1N1 virus has affected the Chinese swine industry, and human infection cases have been reported occasionally. However, little is known about the pathogenic mechanism of EA H1N1 virus. In this study, we compared the mouse pathogenicity of A/swine/Guangdong/YJ4/2014 [...] Read more.
The Eurasian avian-like swine (EA) H1N1 virus has affected the Chinese swine industry, and human infection cases have been reported occasionally. However, little is known about the pathogenic mechanism of EA H1N1 virus. In this study, we compared the mouse pathogenicity of A/swine/Guangdong/YJ4/2014 (YJ4) and A/swine/Guangdong/MS285/2017 (MS285) viruses, which had similar genotype to A/Hunan/42443/2015 (HuN-like). None of the mice inoculated with 106 TCID50 of YJ4 survived at 7 days post infection, while the survival rate of the MS285 group was 100%. Therefore, a series of single fragment reassortants in MS285 background and two rescued wild-type viruses were generated by using the reverse genetics method, and the pathogenicity analysis revealed that the PB2 gene contributed to the high virulence of YJ4 virus. Furthermore, there were 11 amino acid differences in PB2 between MS285 and YJ4 identified by sequence alignment, and 11 single amino acid mutant viruses were generated in the MS285 background. We found that the R251K mutation significantly increased the virulence of MS285 in mice, contributed to high polymerase activity and enhanced viral genome transcription and replication. These results indicate that PB2-R251K contributes to the virulence of the EA H1N1 virus and provide new insight into future molecular epidemiological surveillance strategies. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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Review

Jump to: Research

20 pages, 1206 KiB  
Review
The Effects of Genetic Variation on H7N9 Avian Influenza Virus Pathogenicity
by Szu-Wei Huang and Sheng-Fan Wang
Viruses 2020, 12(11), 1220; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111220 - 28 Oct 2020
Cited by 10 | Viewed by 4083
Abstract
Since the H7N9 avian influenza virus emerged in China in 2013, there have been five seasonal waves which have shown human infections and caused high fatality rates in infected patients. A multibasic amino acid insertion seen in the HA of current H7N9 viruses [...] Read more.
Since the H7N9 avian influenza virus emerged in China in 2013, there have been five seasonal waves which have shown human infections and caused high fatality rates in infected patients. A multibasic amino acid insertion seen in the HA of current H7N9 viruses occurred through natural evolution and reassortment, and created a high pathogenicity avian influenza (HPAI) virus from the low pathogenicity avian influenza (LPAI) in 2017, and significantly increased pathogenicity in poultry, resulting in widespread HPAI H7N9 in poultry, which along with LPAI H7N9, contributed to the severe fifth seasonal wave in China. H7N9 is a novel reassorted virus from three different subtypes of influenza A viruses (IAVs) which displays a great potential threat to public health and the poultry industry. To date, no sustained human-to-human transmission has been recorded by the WHO. However, the high ability of evolutionary adaptation of H7N9 and lack of pre-existing immunity in humans heightens the pandemic potential. Changes in IAVs proteins can affect the viral transmissibility, receptor binding specificity, pathogenicity, and virulence. The multibasic amino acid insertion, mutations in hemagglutinin, deletion and mutations in neuraminidase, and mutations in PB2 contribute to different virological characteristics. This review summarized the latest research evidence to describe the impacts of viral protein changes in viral adaptation and pathogenicity of H7N9, aiming to provide better insights for developing and enhancing early warning or intervention strategies with the goal of preventing highly pathogenic IAVs circulation in live poultry, and transmission to humans. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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20 pages, 2393 KiB  
Review
Controlling Avian Influenza Virus in Bangladesh: Challenges and Recommendations
by Rokshana Parvin, Mohammed Nooruzzaman, Congriev Kumar Kabiraj, Jahan Ara Begum, Emdadul Haque Chowdhury, Mohammad Rafiqul Islam and Timm Harder
Viruses 2020, 12(7), 751; https://0-doi-org.brum.beds.ac.uk/10.3390/v12070751 - 12 Jul 2020
Cited by 20 | Viewed by 6269
Abstract
Avian influenza virus (AIV) remains a huge challenge for poultry production with negative repercussions for micro- and macro-economy and public health in Bangladesh. High (HP) H5N1 and low pathogenicity (LP) H9N2 AIV are currently endemic in poultry, and both have been reported to [...] Read more.
Avian influenza virus (AIV) remains a huge challenge for poultry production with negative repercussions for micro- and macro-economy and public health in Bangladesh. High (HP) H5N1 and low pathogenicity (LP) H9N2 AIV are currently endemic in poultry, and both have been reported to infect humans sporadically. Multiple virus introductions of different clades of HPAIV H5N1, reassorted genotypes, and on-going diversification of LPAIV H9N2 create a highly volatile virological environment which potentially implicates increased virulence, adaptation to new host species, and subsequent zoonotic transmission. Allotropy of poultry rearing systems and supply chains further increase the risk of virus spreading, which leads to human exposure and fosters the emergence of new potentially pre-pandemic virus strains. Here, we review the epidemiology, focusing on (i) risk factors for virus spreading, (ii) viral genetic evolution, and (iii) options for AIV control in Bangladesh. It is concluded that improved control strategies would profit from the integration of various intervention tools, including effective vaccination, enhanced biosecurity practice, and improved awareness of producers and traders, although widespread household poultry rearing significantly interferes with any such strategies. Nevertheless, continuous surveillance associated with rapid diagnosis and thorough virus characterization is the basis of such strategies. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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31 pages, 3816 KiB  
Review
The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses
by Holly Everest, Sarah C. Hill, Rebecca Daines, Joshua E. Sealy, Joe James, Rowena Hansen and Munir Iqbal
Viruses 2020, 12(6), 673; https://0-doi-org.brum.beds.ac.uk/10.3390/v12060673 - 22 Jun 2020
Cited by 20 | Viewed by 6360
Abstract
Avian influenza viruses of the subtype H6Nx are being detected globally with increasing frequency. Some H6Nx lineages are becoming enzootic in Asian poultry and sporadic incursions into European poultry are occurring more frequently. H6Nx viruses that contain mammalian adaptation motifs pose a zoonotic [...] Read more.
Avian influenza viruses of the subtype H6Nx are being detected globally with increasing frequency. Some H6Nx lineages are becoming enzootic in Asian poultry and sporadic incursions into European poultry are occurring more frequently. H6Nx viruses that contain mammalian adaptation motifs pose a zoonotic threat and have caused human cases. Although currently understudied globally, H6Nx avian influenza viruses pose a substantial threat to both poultry and human health. In this review we examine the current state of knowledge of H6Nx viruses including their global distribution, tropism, transmission routes and human health risk. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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14 pages, 239 KiB  
Review
Adaptation of H9N2 Influenza Viruses to Mammalian Hosts: A Review of Molecular Markers
by Xiangjie Sun, Jessica A. Belser and Taronna R. Maines
Viruses 2020, 12(5), 541; https://0-doi-org.brum.beds.ac.uk/10.3390/v12050541 - 14 May 2020
Cited by 32 | Viewed by 4828
Abstract
As the number of human infections with avian and swine influenza viruses continues to rise, the pandemic risk posed by zoonotic influenza viruses cannot be underestimated. Implementation of global pandemic preparedness efforts has largely focused on H5 and H7 avian influenza viruses; however, [...] Read more.
As the number of human infections with avian and swine influenza viruses continues to rise, the pandemic risk posed by zoonotic influenza viruses cannot be underestimated. Implementation of global pandemic preparedness efforts has largely focused on H5 and H7 avian influenza viruses; however, the pandemic threat posed by other subtypes of avian influenza viruses, especially the H9 subtype, should not be overlooked. In this review, we summarize the literature pertaining to the emergence, prevalence and risk assessment of H9N2 viruses, and add new molecular analyses of key mammalian adaptation markers in the hemagglutinin and polymerase proteins. Available evidence has demonstrated that H9N2 viruses within the Eurasian lineage continue to evolve, leading to the emergence of viruses with an enhanced receptor binding preference for human-like receptors and heightened polymerase activity in mammalian cells. Furthermore, the increased prevalence of certain mammalian adaptation markers and the enhanced transmissibility of selected viruses in mammalian animal models add to the pandemic risk posed by this virus subtype. Continued surveillance of zoonotic H9N2 influenza viruses, inclusive of close genetic monitoring and phenotypic characterization in animal models, should be included in our pandemic preparedness efforts. Full article
(This article belongs to the Special Issue Evolution and Pathogenesis of Avian and Animal Influenza Viruses)
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