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United States Department of Agriculture

Agricultural Research Service

Research Project: SWINE VIRAL DISEASES PATHOGENESIS AND IMMUNOLOGY Title: Influenza A virus in swine - moving beyond 2009

Authors
item Vincent, Amy
item Lorusso, Alessio
item Lager, Kelly
item Gauger, Phillip -
item Gramer, Marie -
item Ciacci-Zanella, Janice -

Submitted to: International Symposium on Emerging and Re-Emerging Pig Diseases
Publication Type: Proceedings
Publication Acceptance Date: March 20, 2011
Publication Date: June 12, 2011
Citation: Vincent, A.L., Lorusso, A., Lager, K.M., Gauger, P.C., Gramer, M.R., Ciacci-Zanella, J.R. 2011. Influenza A virus in swine - moving beyond 2009. In: Proceedings of the 6th International Symposium on Emerging and Re-emerging Pig Diseases, June 12-15, 2011, Barcelona, Spain. p. 35-37.

Technical Abstract: Introduction: Surveillance for influenza A viruses (IAV) circulating in pigs and other non-human mammals has been chronically underfunded and virtually nonexistent in many areas of the world [1]. This deficit is in spite of our knowledge that influenza is a disease shared between man and pig from at least as far back as the 1918 Spanish Flu Pandemic. In March-April 2009, a novel pandemic H1N1 emerged in the human population in North America [2] and demonstrated in a public forum the paucity of data on influenza viruses in swine. The gene constellation of the emerging virus was demonstrated to be a combination of genes from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before been identified in swine or other species. The emergent H1N1 quickly spread in the human population and the outbreak reached pandemic level 6 as declared by the World Health Organization on June 11, 2009. Although the 8 gene segments of the novel virus are similar to available sequences of corresponding genes from SIV from North America and Eurasia, no closely related ancestral IAV with this gene combination has been identified in North America or elsewhere in the world [3, 4]. Other than sporadic transmission to humans [5, 6], swine influenza A viruses of the H1N1 subtype historically have been distinct from avian and other mammalian H1N1 influenza viruses in characteristics of host specificity, serologic cross-reactivity, and/or nucleotide sequence. The emergence of the 2009 pandemic H1N1 (pH1N1) virus brought a heightened awareness to the evolution and epidemiology of influenza A viruses in swine and presents a new era of challenges and opportunities for understanding and controlling influenza in pigs. North American triple reassortant swine viruses. Swine influenza was first recognized in pigs in the Midwestern U.S. in 1918 as a respiratory disease that coincided with the human pandemic known as the Spanish flu. Since then, it has become an important disease to the swine industry throughout the world. The first influenza virus was isolated in 1930 by Shope [7] and was demonstrated to cause respiratory disease in swine that was similar to human influenza. The classical swine lineage H1N1 (cH1N1) derived from the 1918 pandemic was relatively stable at the genetic and antigenic levels in U.S. swine. The epidemiology of IAV in pigs dramatically changed after 1998 when triple reassortant viruses containing gene segments from the classical swine virus (NP, M, NS), human virus (PB1, HA, NA), and avian virus (PB2, PA) [8] became successfully established in the pig population [9]. The human lineage PB1, avian lineage PB2 and PA and swine lineage NP, M, and NS found in contemporary swine influenza viruses are referred to as the triple reassortant internal gene (TRIG) constellation [10] and the vast majority of the characterized swine viruses from the U.S. and Canada contain the TRIG, regardless of subtype. After their emergence, the H3N2 viruses reassorted with cH1N1 swine IAV [11, 12]. Reassortant H1 viruses are endemic with the H3N2 viruses in most major swine producing regions of the U.S. and Canada. Since 2005, H1N1 and H1N2 viruses with the HA gene derived from human viruses emerged and spread across the U.S. in swine herds [13]. The HAs from the human-like swine H1 viruses are genetically and antigenically distinct from classical swine lineage H1s. However, their TRIG genes are similar to those found in the TRIG cassette of the contemporary swine triple reassortant viruses. To represent the evolution of the currently circulating North American H1 viruses, a cluster classification has been proposed. Viruses from the classical H1N1 lineage-HA evolved to form alpha-, beta-, and gamma-clusters based on the genetic makeup of the HA gene; whereas H1 subtypes strains with HA genes most similar to human seasonal H1 viruses form the delta-cluster [13]. All four HA gene cluster types can be found with neuraminidase genes of either the N1 or N2 subtype. The HA from the delta-cluster viruses were shown to have most likely emerged from two separate introductions of human seasonal HA from H1N2 and H1N1 viruses and are differentiated phylogenetically by two distinct sub-clusters, delta1 and delta2, respectively [14]. HAs of the delta-cluster were paired either with an N1 or N2 gene of human virus lineage and not of swine N1 lineage. The H1 SIV are evolving by drift and shift while maintaining the TRIG backbone and the resulting viruses differ genetically and antigenically with obvious consequences for vaccine and diagnostic test development [14]. Eurasian viruses. Swine IAV with genetic lineages that are distinct from the North American TRIG viruses evolved in Europe and Asia (reviewed in [15]). Although cH1N1 swine viruses previously circulated in Europe, Asia, and many other parts of the world, they were eventually replaced by a new lineage in Europe, a wholly avian H1N1 that emerged in 1979. The avian-lineage H1N1 was subsequently identified in Asia in 1993. Human-lineage H3N2 distinct from those in North America also emerged in Europe and Asia in the 1970s. Additionally, a human-like H1N2 emerged in pigs in Great Britain in the 1990s. A recent European surveillance study reported the continued circulation of avian-like H1N1, human-like H3N2 and human-like H1N2 in swine. All three subtypes were detected in Belgium, Italy and Spain, while only H1N1 and H1N2 viruses were found in UK and Northwestern France [16]. The epidemiology of influenza viruses in Asia is complicated by the presence of North American and European lineage viruses, subsequent reassortant swine viruses between the two lineages, and reports of unique avian-lineage viruses. A complete description of IAV in Asian swine is beyond the scope of this paper. Pandemic H1N1 (2009). The pH1N1 possesses a unique genome with six gene segments (PB2, PB1, PA, HA, NP and NS) with the closest known genetic lineage being the triple-reassortant influenza viruses of the North American swine lineage and the M and NA genes derived from a Eurasian lineage of swine influenza viruses [17]. The 2009 pandemic influenza became infamously known as "swine flu" due to the phylogenetic origin of the gene segments. However, the unique combination of gene segments had never before been recognized in swine and since the recognition of the pandemic, the epidemiology in humans has not been affected by the subsequent human to pig transmission and outbreaks in pigs [17]. The initial documented swine outbreaks were preceded by reported human influenza-like illness during the pandemic [18]. The 2009 pH1N1 was shown to replicate efficiently in the lower and upper respiratory tract of experimentally infected pigs and to cause a clinical disease comparable to that typically observed during common enzootic influenza virus infection in swine [19-21]. Early reference to the 2009 pH1N1 as "swine flu" led to unnecessary alarm over the safety of pork meat products and culminated in the ban of exported pork from the U.S. by several countries, resulting in billions of dollars in lost revenue for the U.S. swine industry. However, contamination of fresh pork meat with the novel virus was experimentally excluded [22]. Immediately after the onset in humans, cases of infection of pigs with the p2009 H1N1 were reported in different areas of the world. The first case was detected on April 28, 2009 in Canada in a farm with pigs that were not previously vaccinated against swine influenza [18, 23]. Based on observations thus far, it is likely that the virus will continue to jump from humans to susceptible pigs with subsequent pig-to-pig transmission and establishment of yet another endemic virus in swine populations around the world. The 2009 pH1N1, a virus shared between people and pigs, has the potential to further change the epidemiology of influenza viruses in human and swine populations. None of the 8 genes of the 2009 pH1

Last Modified: 4/20/2014
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