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      Are pigs overestimated as a source of zoonotic influenza viruses?

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          Abstract

          Background

          Swine influenza caused by influenza A viruses (IAV) directly affects respiratory health and indirectly impairs reproduction rates in pigs causing production losses. In Europe, and elsewhere, production systems have intensified featuring fewer holdings but, in turn, increased breeding herd and litter sizes. This seems to foster swine IAV (swIAV) infections with respect to the entrenchment within and spread between holdings. Disease management of swine influenza is difficult and relies on biosecurity and vaccination measures. Recently discovered and widely proliferating forms of self-sustaining modes of swIAV infections in large swine holdings challenge these preventive concepts by generating vaccine-escape mutants in rolling circles of infection.

          Main body

          The most recent human IAV pandemic of 2009 rooted at least partly in IAV of porcine origin highlighting the zoonotic potential of swIAV. Pigs constitute a mixing vessel of IAV from different species including avian and human hosts. However, other host species such as turkey and quail but also humans themselves may also act in this way; thus, pigs are not essentially required for the generation of IAV reassortants with a multispecies origin. Since 1918, all human pandemic influenza viruses except the H2N2 virus of 1958 have been transmitted in a reverse zoonotic mode from human into swine populations. Swine populations act as long-term reservoirs of these viruses. Human-derived IAV constitute a major driver of swIAV epidemiology in pigs. Swine-to-human IAV transmissions occurred rarely and mainly sporadically as compared to avian-to-human spill-over events of avian IAV. Yet, new swIAV variants that harbor zoonotic components continue to be detected. This increases the risk that such components might eventually reassort into viruses with pandemic potential.

          Conclusions

          Domestic pig populations should not be globally stigmatized as the only or most important reservoir of potentially zoonotic IAV. The likely emergence from swine of the most recent human IAV pandemic in 2009, however, emphasized the principal risks of swine populations in which IAV circulate unimpededly. Implementation of regular and close-meshed IAV surveillance of domestic swine populations to follow the dynamics of swIAV evolution is clearly demanded. Improved algorithms for directly inferring zoonotic potential from whole IAV genome sequences as well as improved vaccines are still being sought.

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          Most cited references97

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          Avian flu: influenza virus receptors in the human airway.

          Although more than 100 people have been infected by H5N1 influenza A viruses, human-to-human transmission is rare. What are the molecular barriers limiting human-to-human transmission? Here we demonstrate an anatomical difference in the distribution in the human airway of the different binding molecules preferred by the avian and human influenza viruses. The respective molecules are sialic acid linked to galactose by an alpha-2,3 linkage (SAalpha2,3Gal) and by an alpha-2,6 linkage (SAalpha2,6Gal). Our findings may provide a rational explanation for why H5N1 viruses at present rarely infect and spread between humans although they can replicate efficiently in the lungs.
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            Influenza

            Influenza is an infectious respiratory disease that, in humans, is caused by influenza A and influenza B viruses. Typically characterized by annual seasonal epidemics, sporadic pandemic outbreaks involve influenza A virus strains of zoonotic origin. The WHO estimates that annual epidemics of influenza result in ~1 billion infections, 3–5 million cases of severe illness and 300,000–500,000 deaths. The severity of pandemic influenza depends on multiple factors, including the virulence of the pandemic virus strain and the level of pre-existing immunity. The most severe influenza pandemic, in 1918, resulted in >40 million deaths worldwide. Influenza vaccines are formulated every year to match the circulating strains, as they evolve antigenically owing to antigenic drift. Nevertheless, vaccine efficacy is not optimal and is dramatically low in the case of an antigenic mismatch between the vaccine and the circulating virus strain. Antiviral agents that target the influenza virus enzyme neuraminidase have been developed for prophylaxis and therapy. However, the use of these antivirals is still limited. Emerging approaches to combat influenza include the development of universal influenza virus vaccines that provide protection against antigenically distant influenza viruses, but these vaccines need to be tested in clinical trials to ascertain their effectiveness.
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              Characterization of the 1918 influenza virus polymerase genes.

              The influenza A viral heterotrimeric polymerase complex (PA, PB1, PB2) is known to be involved in many aspects of viral replication and to interact with host factors, thereby having a role in host specificity. The polymerase protein sequences from the 1918 human influenza virus differ from avian consensus sequences at only a small number of amino acids, consistent with the hypothesis that they were derived from an avian source shortly before the pandemic. However, when compared to avian sequences, the nucleotide sequences of the 1918 polymerase genes have more synonymous differences than expected, suggesting evolutionary distance from known avian strains. Here we present sequence and phylogenetic analyses of the complete genome of the 1918 influenza virus, and propose that the 1918 virus was not a reassortant virus (like those of the 1957 and 1968 pandemics), but more likely an entirely avian-like virus that adapted to humans. These data support prior phylogenetic studies suggesting that the 1918 virus was derived from an avian source. A total of ten amino acid changes in the polymerase proteins consistently differentiate the 1918 and subsequent human influenza virus sequences from avian virus sequences. Notably, a number of the same changes have been found in recently circulating, highly pathogenic H5N1 viruses that have caused illness and death in humans and are feared to be the precursors of a new influenza pandemic. The sequence changes identified here may be important in the adaptation of influenza viruses to humans.
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                Author and article information

                Contributors
                timm.harder@fli.de
                Journal
                Porcine Health Manag
                Porcine Health Manag
                Porcine Health Management
                BioMed Central (London )
                2055-5660
                30 June 2022
                30 June 2022
                2022
                : 8
                : 30
                Affiliations
                [1 ]GRID grid.417834.d, Institute of Diagnostic Virology, , Friedrich-Loeffler-Institut, ; Suedufer 10, 17493 Greifswald-Insel Riems, Germany
                [2 ]GRID grid.5963.9, Institute of Virology, Medical Center, , University of Freiburg, ; 79104 Freiburg, Germany
                [3 ]GRID grid.5963.9, Faculty of Medicine, , University of Freiburg, ; 79104 Freiburg, Germany
                [4 ]GRID grid.5963.9, Spemann Graduate School of Biology and Medicine, , University of Freiburg, ; 79104 Freiburg, Germany
                Article
                274
                10.1186/s40813-022-00274-x
                9244577
                35773676
                052fd488-d5ed-48d1-985f-646ae81baa0c
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 21 March 2022
                : 20 June 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: 434507207
                Award ID: SFB 1160
                Funded by: FundRef http://dx.doi.org/10.13039/100010661, Horizon 2020 Framework Programme under Grant agreement ID 862605 (consortium PIGIE);
                Award ID: 2821ERA24D
                Funded by: Friedrich-Loeffler-Institut, Bundesforschungsinstitut für Tiergesundheit (4246)
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                swine influenza a virus,mixing vessel,zoonotic potential,reverse zoonosis,surveillance

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