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Genetic variations of nucleoprotein gene of influenza A viruses isolated from swine in Thailand.

ABSTRACT: BACKGROUND: Influenza A virus causes severe disease in both humans and animals and thus, has a considerably impact on economy and public health. In this study, the genetic variations of the nucleoprotein (NP) gene of influenza viruses recovered from swine in Thailand were determined. RESULTS: Twelve influenza A virus specimens were isolated from Thai swine. All samples were subjected to nucleotide sequencing of the complete NP gene. Phylogenetic analysis was conducted by comparing the NP gene of swine influenza viruses with that of seasonal and pandemic human viruses and highly pathogenic avian viruses from Thailand (n = 77). Phylogenetic analysis showed that the NP gene from different host species clustered in distinct host specific lineages. The NP gene of swine influenza viruses clustered in either Eurasian swine or Classical swine lineages. Genetic analysis of the NP gene suggested that swine influenza viruses circulating in Thailand display 4 amino acids unique to Eurasian and Classical swine lineages. In addition, the result showed 1 and 5 amino acids unique to avian and human lineages, respectively. Furthermore, nucleotide substitution rates showed that the NP gene is highly conserved especially in avian influenza viruses. CONCLUSION: The NP gene sequence of influenza A in Thailand is highly conserved within host-specific lineages and shows amino acids potentially unique to distinct NP lineages. This information can be used to investigate potential interspecies transmission of influenza A viruses. In addition, the genetic variations of the NP gene will be useful for monitoring the viruses and preparing effective prevention and control strategies for potentially pandemic influenza outbreaks.

SUBMITTER: Thippamom N

PROVIDER: S-EPMC2924863 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Genetic variations of nucleoprotein gene of influenza A viruses isolated from swine in Thailand.

Thippamom Nattakarn N Sreta Donreuthai D Kitikoon Pravina P Thanawongnuwech Roongroje R Poovorawan Yong Y Theamboonlers Apiradee A Suwannakarn Kamol K Parchariyanon Sujira S Damrongwatanapokin Sudarat S Amonsin Alongkorn A

Virology journal 20100809

<h4>Background</h4>Influenza A virus causes severe disease in both humans and animals and thus, has a considerably impact on economy and public health. In this study, the genetic variations of the nucleoprotein (NP) gene of influenza viruses recovered from swine in Thailand were determined.<h4>Results</h4>Twelve influenza A virus specimens were isolated from Thai swine. All samples were subjected to nucleotide sequencing of the complete NP gene. Phylogenetic analysis was conducted by comparing t ...[more]

PMID: 20696044

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Project description:A phylogenetic analysis of 52 published and 37 new nucleoprotein (NP) gene sequences addressed the evolution and origin of human and swine influenza A viruses. H1N1 human and classical swine viruses (i.e., those related to Swine/Iowa/15/30) share a single common ancestor, which was estimated to have occurred in 1912 to 1913. From this common ancestor, human and classical swine virus NP genes have evolved at similar rates that are higher than in avian virus NP genes (3.31 to 3.41 versus 1.90 nucleotide changes per year). At the protein level, human virus NPs have evolved twice as fast as classical swine virus NPs (0.66 versus 0.34 amino acid change per year). Despite evidence of frequent interspecies transmission of human and classical swine viruses, our analysis indicates that these viruses have evolved independently since well before the first isolates in the early 1930s. Although our analysis cannot reveal the original host, the ancestor virus was avianlike, showing only five amino acid differences from the root of the avian virus NP lineage. The common pattern of relationship and origin for the NP and other genes of H1N1 human and classical swine viruses suggests that the common ancestor was an avian virus and not a reassortant derived from previous human or swine influenza A viruses. The new avianlike H1N1 swine viruses in Europe may provide a model for the evolution of newly introduced avian viruses into the swine host reservoir. The NPs of these viruses are evolving more rapidly than those of human or classical swine viruses (4.50 nucleotide changes and 0.74 amino acid change per year), and when these rates are applied to pre-1930s human and classical swine virus NPs, the predicted date of a common ancestor is 1918 rather than 1912 to 1913. Thus, our NP phylogeny is consistent with historical records and the proposal that a short time before 1918, a new H1N1 avianlike virus entered human or swine hosts (O. T. Gorman, R. O. Donis, Y. Kawaoka, and R. G. Webster, J. Virol. 64:4893-4902, 1990). This virus provided the ancestors of all known human influenza A virus genes, except for HA, NA, and PB1, which have since been reassorted from avian viruses. We propose that during 1918 a virulent strain of this new avianlike virus caused a severe human influenza pandemic and that the pandemic virus was introduced into North American swine populations, constituting the origin of classical swine virus.

Project description:To cross the human species barrier, influenza A viruses (IAV) of avian origin have to overcome the interferon-induced host restriction factor MxA by acquiring distinct mutations in their nucleoprotein (NP). We recently demonstrated that North American classical swine IAV are able to partially escape MxA restriction. Here we investigated whether the Eurasian avian-like swine IAV lineage currently circulating in European swine would likewise evade restriction by human MxA. We found that the NP of the influenza virus isolate A/Swine/Belzig/2/2001 (Belzig-NP) exhibits increased MxA escape, similar in extent to that with human IAV NPs. Mutational analysis revealed that the MxA escape mutations in Belzig-NP differ from the known MxA resistance cluster of the North American classical swine lineage and human-derived IAV NPs. A mouse-adapted avian IAV of the H7N7 subtype encoding Belzig-NP showed significantly greater viral growth in both MxA-expressing cells and MxA-transgenic mice than control viruses lacking the MxA escape mutations. Similarly, the growth of the recombinant Belzig virus was only marginally affected in MxA-expressing cells and MxA-transgenic mice, in contrast to that of Belzig mutant viruses lacking MxA escape mutations in the NP. Phylogenetic analysis of the Eurasian avian-like swine IAV revealed that the NP amino acids required for MxA escape were acquired successively and were maintained after their introduction. Our results suggest that the circulation of IAV in the swine population can result in the selection of NP variants with a high degree of MxA resistance, thereby increasing the zoonotic potential of these viruses.IMPORTANCE The human MxA protein efficiently blocks the replication of IAV from nonhuman species. In rare cases, however, these IAV overcome the species barrier and become pandemic. All known pandemic viruses have acquired and maintained MxA escape mutations in the viral NP and thus are not efficiently controlled by MxA. Intriguingly, partial MxA resistance can also be acquired in other hosts that express antivirally active Mx proteins, such as swine. To perform a risk assessment of IAV circulating in the European swine population, we analyzed the degree of MxA resistance of Eurasian avian-like swine IAV. Our data demonstrate that these viruses carry formerly undescribed Mx resistance mutations in the NP that mediate efficient escape from human MxA. We conclude that Eurasian avian-like swine IAV possess substantial zoonotic potential.

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Genetic variations of nucleoprotein gene of influenza A viruses isolated from swine in Thailand.

Publications

Genetic variations of nucleoprotein gene of influenza A viruses isolated from swine in Thailand.

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