Diversity of Influenza Viruses in Swine and the Emergence of a Novel Human Pandemic Influenza A (H1N1)

Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Influenza and Other Respiratory Viruses (Impact Factor: 2.2). 09/2009; 3(5):207-13. DOI: 10.1111/j.1750-2659.2009.00096.x
Source: PubMed


The novel H1N1 influenza virus that emerged in humans in Mexico in early 2009 and transmitted efficiently in the human population with global spread has been declared a pandemic strain. Here we review influenza infections in swine since 1918 and the introduction of different avian and human influenza virus genes into swine influenza viruses of North America and Eurasia. These introductions often result in viruses of increased fitness for pigs that occasionally transmit to humans. The novel virus affecting humans is derived from a North American swine influenza virus that has acquired two gene segments [Neuraminidase (NA) and Matrix (M)] from the European swine lineages. This reassortant appears to have increased fitness in humans. The potential for increased virulence in humans and of further reassortment between the novel H1N1 influenza virus and oseltamivir resistant seasonal H1N1 or with highly pathogenic H5N1 influenza stresses the need for urgent pandemic planning.

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    • "Influenza A viruses (IAVs) have a genome consisting of 8 segmented , negative-sense and single-stranded RNAs, which encode 8 major structural proteins and two nonstructural (NS) proteins as well as other minor proteins [1] [2]. Due to the nature of their genome, IAVs have the potential to generate variants through a reassortment process, which is a swapping of gene segments in a cell co-infected with two different strains of IAVs [3] [4]. Genetic reassortment played a critical role in the appearance of pandemic IAVs in 1957, 1968, and 2009 [5]. "
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    ABSTRACT: By nature of their segmented RNA genome, influenza A viruses (IAVs) have the potential to generate variants through a reassortment process. The influenza nonstructural (NS) gene is critical for a virus to counteract the antiviral responses of the host. Therefore, a newly acquired NS segment potentially determines the replication efficiency of the reassortant virus in a range of different hosts. In addition, the C-terminal PDZ-binding motif (PBM) has been suggested as a pathogenic determinant of IAVs. To gauge the pandemic potential from human and avian IAV reassortment, we assessed the replication properties of NS-reassorted viruses in cultured cells and in the lungs of mice and determined their transmissibility in guinea pigs. Compared with the recombinant A/Korea/01/2009 virus (rK09; 2009 pandemic H1N1 strain), the rK09/VN:NS virus, in which the NS gene was adopted from the A/Vietnam/1203/2004 virus (a human isolate of the highly pathogenic avian influenza H5N1 virus strains), exhibited attenuated virulence and reduced transmissibility. However, the rK09/VN:NS-PBM virus, harboring the PBM in the C-terminus of the NS1 protein, recovered the attenuated virulence of the rK09/VN:NS virus. In a guinea pig model, the rK09/VN:NS-PBM virus showed even greater transmission efficiency than the rK/09 virus. These results suggest that the PBM in the NS1 protein may determine viral persistence in the human and avian IAV interface.
    Preview · Article · Jun 2014 · Biochemical and Biophysical Research Communications
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    • "Genetic analysis confirmed that it was a triple reassorted virus from human, swine, and avian lineages. The virus carried the HA, NP, and NS genes of classical swine virus origin, the PB2 and PA genes from North American avian viruses, the PB1 gene from viruses of human origin and the NA and M genes from Eurasian swine avian-like viruses [Brockwell-Staats et al., 2009; Garten et al., 2009; Peiris et al., 2009]. Molecular analysis of A(H1N1)pdm09 strains had classified them into seven discrete genetic clades [Nelson et al., 2009] which were also confirmed by several "
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    ABSTRACT: The pandemic H1N1 strain of Influenza A virus [A(H1N1)pdm09] is now well adapted in human populations. However, it is still causing sporadic outbreaks worldwide with different severity. The present study was planned to understand the genetic diversity (based on the HA1 gene) of influenza A(H1N1)pdm09 strains circulating during the post pandemic period. The HA1 gene was selected because the HA1 protein is immunogenic, functions as a receptor binding site and indirectly affects transmission and pathogenicity of virus. A total of 2,818 cases were enrolled. Nasal/throat swabs from all cases were tested by one-step real time PCR for detection of influenza virus types and subtypes according to the CDC protocol. Of these, 134 cases were A(H1N1)pdm09 positive, 34 of which were screened for HA1 gene (position 434–905) sequencing (Big-Dye terminator using 3130 ABI, Genetic analyzer). Molecular and phylogenetic analysis was performed using PhyML approach (v. 3.0). All A(H1N1)pdm09 positive and negative cases were clinically characterized. Phylogentically, all Lucknow strains (n = 33) except one fall with the clade seven reference strain. One strain showed 99.9% similarities with clade one reference strain A/California/07/2009. In mutational analysis, 33 strains had the S220T mutation, which is at an antigenic site and characteristic of clade seven along with few minor mutations; K180I/T/Q, V190I, S200P, S202T, A203T, A214T, S220T, V251I, and A273T. These results suggest that clade seven was the most widely circulating clade in Lucknow and A(H1N1)pdm09 cases showed mild clinical symptoms as compared to A(H3N2) or influenza B cases. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Apr 2014 · Journal of Medical Virology
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    • "This virus retained gene constellation of avian (PB2 and PA), human (PB1, HA, and NA), and CS lineages (NP, M, and NS) [11]. Since then, the triple-reassortant virus has gone through multiple reassortment events and thus it diverged into various evolution routes of IAVs [12]. During these reassortment events, the triple-reassortant internal genes (TRIG) have been a gene cassette for accepting different HA and/or NA genes from other contemporary human and swine IAVs [13]. "
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    ABSTRACT: Influenza A virus (IAV) can infect avian and mammalian species, including humans. The genome nature of IAVs may contribute to viral adaptation in different animal hosts, resulting in gene reassortment and the reproduction of variants with optimal fitness. As seen again in the 2009 swine-origin influenza A H1N1 pandemic, pigs are known to be susceptible to swine, avian, and human IAVs and can serve as a 'mixing vessel' for the generation of novel IAV variants. To this end, the emergence of swine influenza viruses must be kept under close surveillance. Herein, we report the isolation and phylogenetic study of a swine IAV, A/swine/Korea/PL01/2012 (swPL01, H3N2 subtype). After screening nasopharyngeal samples from pigs in the Gyeongsangnam-do region of Korea from December 2011 to May 2012, we isolated the swPL01 virus and sequenced its all of 8 genome segments (polymerase basic 2, PB2; polymerase basic 1, PB1; polymerase acidic, PA; hemagglutinin, HA; nucleocapsid protein, NP; neuraminidase, NA; matrix protein, M; and nonstructural protein, NS). The phylogenetic study, analyzed with reference strains registered in the National Center for Biotechnology Information (NCBI) database, indicated that the swPL01 virus was similar to the North American triple-reassortant swine strains and that the HA gene of the swPL01 virus was categorized into swine H3 cluster IV. The swPL01 virus had the M gene of the triple-reassortant swine H3N2 viruses, whereas that of other contemporary strains in Korea was transferred from the 2009 pandemic H1N1 virus. These data suggest the possibility that various swine H3N2 viruses may co-circulate in Korea, which underlines the importance of a sustained surveillance system against swine IAVs.
    Full-text · Article · Feb 2014 · PLoS ONE
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