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United States Department of Agriculture

Agricultural Research Service

Research Project: H1N1 INFLUENZA A VIRUS IN SWINE SUPPLEMENTAL RESEARCH PROGRAM Title: Swine influenza virus: epidemiology and vaccine concerns

item Gauger, Phillip -
item Vincent, Amy

Submitted to: Swine Disease Conference Proceedings
Publication Type: Proceedings
Publication Acceptance Date: November 10, 2011
Publication Date: November 10, 2012
Citation: Gauger, P.C., Vincent, A.L. 2012. Swine influenza virus: epidemiology and vaccine concerns. In: Proceedings of the 19th Annual Swine Disease Conference for Swine Practitioners, November 10-11, 2011, Ames, Iowa. p. 13-21.

Technical Abstract: Introduction. Swine influenza virus (SIV) is a primary cause of respiratory disease in swine and a component of the porcine respiratory disease complex (PRDC). Influenza viruses are an important health and economic concern for swine producers throughout the world. Swine operations may be affected by seasonal infections or endemic circulation of SIV's resulting in high morbidity but typically low mortality. Infection with SIV manifests as an acute onset of respiratory disease characterized by fever, lethargy, anorexia, respiratory distress, coughing, conjunctivitis and nasal discharge (Alexander and Brown, 2000; McQueen et al., 1968; Olson et al., 1999; Richt et al., 2003). Reproductive failure associated with SIV-induced fever has also been documented, which may include infertility, abortions and weak-born piglets (Karasin et al., 2000; Wallace and Elm, Jr., 1979; Wesley, 2004). Influenza is a zoonotic viral disease that represents a health and economic threat to both humans and animals worldwide. The epidemiology of influenza viruses in swine has become more complicated after the introduction of the human-swine-avian lineage triple reassortant influenza virus in 1998. The rate of genetic change within the different subtypes has dramatically increased, antigenic variants of the virus are emerging at a rapid pace, the disease does not consistently follow a predictable seasonal pattern as in the past and vaccines often lack adequate cross-protection against these emerging diverse strains. In addition, the genetic similarity between swine and human influenza viruses and the ease of transmission between these populations suggests a change in the terminology away from "swine influenza virus" to the more generic "influenza A viruses" (IAV) in swine is appropriate. The complex ecology and epidemiology characteristic of contemporary IAV's may be attributed to unique characteristics and interactions between the virus, the host (swine) and three events that have had an impact on the evolution of IAV's in swine. These include the introduction of the triple reassortant viruses in North American swine in 1998, introduction of human seasonal H1 viruses in North American swine in 2005 and the 2009 swine-origin H1N1 influenza pandemic. The Virus. Influenza A viruses in swine are members of the Orthomyxoviridae family with segmented, single-stranded, negative-sense RNA genomes (Knipe et al., 2007). The surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are important to the pathogenesis and life cycle of influenza viruses and are the targets of the host humoral immune response (Cox et al., 2004). Only the H1, H3, N1 and N2 subtypes are endemic and currently circulate in North American swine. The HA and NA genes may vary due to two types of processes known as antigenic drift and antigenic shift. Drift results in minor changes in the genome due to polymerase errors during replication and occurs more commonly in RNA viruses in general. Antigenic shift occur when two or more viruses infect the same cell and exchange entire HA or NA gene segments resulting in a reassortant virus. Prior human influenza pandemics were the result of antigenic shift or a complete species jump of avian IAV to humans (Kawaoka et al., 1989). The Host. Swine are a natural host for influenza viruses. The HA protein is responsible for viral attachment and entry into the host respiratory epithelial cell where the virus replicates. Lesions induced by influenza virus infection include a necrotizing bronchiolitis and interstitial pneumonia. The HA plays a critical role in the restriction of interspecies transmission of influenza viruses based on the specific binding capacity of the HA protein and it's affinity for the host cell receptor. Influenza viruses bind to sialic acid receptors located on the surface of respiratory epithelial cells. However, mammalian and avian influenza viruses have different preferences for binding sialic acid receptors, the alpha-2,6- and alpha-2,3-linked sialyloligosaccharides, respectively. Swine, like many other mammalian species, contain both types of sialic acid receptors in their respiratory tract and are susceptible to infection with either or both mammalian and avian influenza viruses. This physiology was first described for swine and was thus suggested that swine may be a "mixing vessel" for avian and human influenza viruses resulting in reassortant viruses with novel combinations of swine, human or avian genes. The overall concern is that the subsequent reassortant viruses may have the potential to infect humans or be responsible for the next pandemic influenza outbreak. Historical Perspective. Genetic analysis has confirmed the first influenza viruses in swine were similar to the 1918 virus that coincided with the human pandemic known as the Spanish flu (Koen, 1919). The virus was isolated from pigs in 1930 and belonged to the H1N1 lineage (Shope, 1931). Swine were subsequently used as a model to study influenza pathogenesis in a natural host. Influenza A viruses in swine that demonstrate similar genetic characteristics to the 1930 virus are currently designated classical H1N1 viruses (cH1N1). For over 70 years, the cH1N1 virus remained relatively stable at the genetic and antigenic level and was the only subtype responsible for acute influenza outbreaks of respiratory disease in swine in the United States. It is unknown why additional subtypes did not infect pigs during this extended period, although production practices based on smaller groups of pigs, limited movement of swine and restricted exposure to humans may have contributed to this lack of variability. Current Perspective. In 1998, the introduction of IAVs of the H3N2 subtype into North American swine may be considered the most critical event that shaped the future epidemiology of IAV's in swine. A severe influenza-like disease was observed in swine in North Carolina as well as Texas, Minnesota and Iowa. Genetic analysis of these H3N2 viruses isolated from multiple cases demonstrated the presence of two genotypes. A North Carolina isolate was a double reassortant with gene segments similar to those of the cH1N1 swine lineage (PA, PB2, M, NP, NS) but also included human lineage hemagglutinin (HA), neuraminidase (NA) and PB1 genes. Influenza viruses isolated from swine in Iowa, Minnesota and Texas were triple reassortants containing gene segments from the cH1N1 lineage (NS, NP, M), and also included segments from avian lineage (PB2, PA) and the same human lineage virus as the double reassortant H3N2 viruses (HA, NA, PB1) (Zhou et al., 1999). Within one year, the triple reassortant influenza viruses in swine became widespread in the US and with time replaced the cH1N1, suggesting the unique combination of swine, avian and human gene segments may have provided a selective advantage over other influenza viruses in swine (Webby et al., 2000). The double reassortants detected at that time never became endemic in swine. H1 viruses in North American swine. The six internal gene segments of the triple reassortant influenza viruses that includes the PB1 of human lineage, PA and PB2 of avian lineage and NP, M and NS of swine lineage is known as the triple reassortant internal gene constellation or 'TRIG' cassette. The vast majority of the contemporary influenza viruses isolated from swine in the US and Canada contain the TRIG regardless of subtype. Shortly after the introduction of H3N2 viruses in 1998, reassortant viruses began to emerge in swine. The cH1N1 and H3N2 reassortant viruses contained the HA and NA genes from the cH1N1 and TRIG from H3N2 viruses. These viruses are referred to as reassortant H1N1 (rH1N1) virus (Karasin et al., 2000; Webby et al., 2004). Reassortant swine influenza viruses with the HA from the cH1N1 and NA and TRIG from the H3N2 virus are the contemporary H1N2 viruses (Karasin et al., 2000; Webby et al., 2004). All of these subtypes co-circulate in the North American sw

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