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      The pig as a mixing vessel for influenza viruses: Human and veterinary implications

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          Abstract

          Influenza A viruses are highly infectious respiratory pathogens that can infect many species. Birds are the reservoir for all known influenza A subtypes; and novel influenza viruses can emerge from birds and infect mammalian species including humans. Because swine are susceptible to infection with both avian and human influenza viruses, novel reassortant influenza viruses can be generated in this mammalian species by reassortment of influenza viral segments leading to the “mixing vessel” theory. There is no direct evidence that the reassortment events culminating in the 1918, 1957 or 1968 pandemic influenza viruses originated from pigs. Genetic reassortment among avian, human and/or swine influenza virus gene segments has occurred in pigs and some novel reassortant swine viruses have been transmitted to humans. Notably, novel reassortant H2N3 influenza viruses isolated from the US pigs, most likely infected with avian influenza viruses through surface water collected in ponds for cleaning barns and watering animals, had a similar genetic make-up to early isolates (1957) of the H2N2 human pandemic. These novel H2N3 swine viruses were able to cause disease in swine and mice and were infectious and highly transmissible in swine and ferrets without prior adaptation. The preceding example shows that pigs could transmit novel viruses from an avian reservoir to other mammalian species. Importantly, H2 viruses pose a substantial risk to humans because they have been absent from mammalian species since 1968 and people born after 1968 have little preexisting immunity to the H2 subtype. It is difficult to predict which virus will cause the next human pandemic and when that pandemic might begin. Importantly, the establishment and spread of a reassorted mammalian-adapted virus from pigs to humans could happen anywhere in the world. Therefore, both human and veterinary research needs to give more attention to potential cross-species transmission capacity of influenza A viruses.

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          Most cited references136

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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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            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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              Update on avian influenza A (H5N1) virus infection in humans.

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                Author and article information

                Journal
                J Mol Genet Med
                jmgm
                Journal of molecular and genetic medicine : an international journal of biomedical research
                Library Publishing Media
                1747-0862
                January 2009
                27 November 2008
                : 3
                : 1
                : 158-166
                Affiliations
                [1 ]Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA
                [2 ]Avian Flu Action, Warrington, Cheshire, United Kingdom
                Author notes
                [* ]Correspondence to: Juergen Richt, jricht@ 123456vet.k-state.edu , Tel: +785 532 2793, Fax: +785 532 4039
                Article
                10.1038/nchina.2008.185
                2702078
                19565018
                6068f951-afcc-455d-a105-53a155ef2314
                © The Authors

                This is an open access article, published under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/). This license permits non-commercial use, distribution and reproduction of the article, provided the original work is appropriately acknowledged with correct citation details.

                History
                : 15 August 2008
                : 5 November 2008
                : 9 November 2008
                Categories
                Review Article

                Molecular medicine
                swine,influenza a virus,mixing vessel,genetic reassortment,human pandemic
                Molecular medicine
                swine, influenza a virus, mixing vessel, genetic reassortment, human pandemic

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