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The emergence of novel influenza viruses among pigs in North America due to interspecies transmission and reassortment
International Congress Series 1263 (2004) 196 – 199
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The emergence of novel influenza viruses among pigs in North America due to interspecies transmission and reassortment Christopher W. Olsen *, Gabriele A. Landolt, Alexander I. Karasin Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53717, USA
Abstract. In 1997 – 1998, H3N2 influenza viruses of different genotypes emerged among North American pigs. Triple reassortant H3N2 viruses containing human, classical swine and avian virus genes spread widely within the swine population and gave rise subsequently to reassortant H1N2 and H1N1 viruses. Together with wholly avian viruses recovered from North American pigs since 1999, these viruses emphasize that influenza virus interspecies transmission and reassortment in pigs can occur throughout world. They provide important research tools with which the genetic factors that control interspecies transmission can be investigated. D 2003 Elsevier B.V. All rights reserved. Keywords: Influenza; Swine; Reassortment; Interspecies transmission; Pandemic
1. Introduction Influenza virus infection in pigs is a cause of economically important respiratory disease in the animals and a human public health concern. Influenza viruses are transmitted from pigs to people as zoonotic agents (reviewed in Ref. [1]) and pigs can serve as hosts for influenza virus reassortment, thus potentially contributing to the creation of pandemic viruses (reviewed in Refs. [2,3]). Southeast Asia has historically been described as an ‘‘epicenter’’ for pandemic viruses (reviewed in Refs. [4,5]), but the viruses that have appeared recently within the swine population of North America (reviewed in Refs. [6,7]) demonstrate that interspecies transmission and reassortment of influenza viruses in pigs can occur anywhere in the world. 2. Emergence of H3N2 influenza viruses among North American pigs Swine influenza in the United States was caused almost exclusively by the ‘‘classical’’ H1N1 swine viruses from the time of their first isolation in 1930 through the mid-1990s * Corresponding author. Tel.: +1-608-265-8681; fax: +1-608-263-0438. E-mail address: [email protected] (C.W. Olsen). 0531-5131/ D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.02.145
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Table 1 Genotypes of the predominant H1N1, H3N2 and H1N2 viruses circulating among American pigs, 1998 – 2003 Gene segment
Classical swine H1N1 viruses
Reassortant H3N2 viruses
Reassortant H1N2 viruses
Reassortant H1N1 viruses
PB2 PB1 PA HA NP NA M NS
swine swine swine swine swine swine swine swine
avian human avian human swine human swine swine
avian human avian swine swine human swine swine
avian human avian swine swine swine swine swine
[8,9]. In 1997– 1998, however, H3N2 viruses appeared among North American pigs [10 – 12]. Genetic analyses of an initial group of nine isolates revealed that 3 different genotypes of H3N2 viruses had emerged independent of one another: a wholly human virus [12]; a reassortant virus containing human and classical swine virus genes [11]; and ‘‘triple reassortant’’ viruses containing genes from human, classical swine and avian viruses [11,12]. Of these, only the triple reassortant viruses have been maintained in the population (Table 1). These are now endemic throughout the American swine population [13] (Olsen et al., unpublished surveillance data). In fact, the wholly human isolate has been shown experimentally to be inherently restricted in its ability to infect pigs [14] and primary swine respiratory epithelial cells (Landolt et al., in preparation), compared with a prototypical triple reassortant virus. 3. Emergence of second generation reassortant H1N2 and H1N1 viruses After 1998, both the triple reassortant H3N2 and classical swine H1N1 viruses cocirculated among American pigs, and both subtypes have been isolated from single swine samples (Olsen et al., unpublished data). Therefore, it is not surprising that additional reassortant genotypes of viruses have also appeared. The first to be recognized were H1N2 viruses that had the ‘‘genetic backbone’’ of the triple reassortant H3N2 viruses, but had acquired an H1 HA gene from a classical swine virus (Table 1) [15]. These H1N2 viruses have become endemic throughout the American swine population [16 –18], and have also been isolated from wild waterfowl [19] and domestic turkeys [20]. Reassortment between the triple reassortant H3N2 (or H1N2) viruses and classical swine H1N1 viruses also created H1N1 viruses containing the human/swine/avian genetic backbone of the reassortant H3N2 and H1N2 viruses, but with both H1 HA and N1 neuraminidase genes from a classical swine virus (Table 1). Interestingly, these reassortant H1N1 viruses were first recognized in a human being [21], but were isolated subsequently from pigs [22]. Our surveillance data (Olsen et al., unpublished data) indicate that they are becoming the predominant form of H1N1 virus isolated from American pigs. 4. Isolation of wholly avian viruses from North American pigs Wholly avian viruses have been isolated from pigs in Canada on three occasions since 1999. These include H1N1 and H3N3 viruses (Olsen et al., in preparation), as well as
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C.W. Olsen et al. / International Congress Series 1263 (2004) 196–199
H4N6 viruses [23]. Of these, the H4N6 viruses isolated from pigs on a farm in Ontario in 1999 are of particular interest because this is a subtype to which the human population is immunologically naı¨ve and, in the course of moving from waterfowl to pigs, this virus had already acquired signature sequences consistent with an ability to utilize the a2,6-linked sialic acid receptors expressed by human respiratory airway cells [23]. Acknowledgements This work was supported by grants from the USDA NRICGP and the University of Wisconsin-Madison School of Veterinary Medicine. The authors thank the following colleagues for providing virus isolates, reagents and/or expertise: Nancy Cox, Lynnette Brammer, Lynn Cooper, Henrietta Hall, Jackie Katz, Alexander Klimov, Catherine Smith, Kanta Subbarao, Sabrina Swenson, John Landgraf, Beverly Schmitt, Dennis Senne, Ian Brown, Suzanne Carman, Keith West, Gary Anderson, Sagar Goyal, Mary Woodruff, Gail Scherba, Gene Erickson, Yoshihiro Kawaoka, James Gern, Rebecca Brockman-Schneider, Gabriele Neumann, Lynette Phillips, Peter Shult, Carol Kirk, Yasou Suzuki and Takashi Suzuki. References [1] C.W. Olsen, Influenza in pigs and their role as the intermediate host, in: K.G. Nicholson, R.G. Webster, A. Hay, N.J. Cox (Eds.), Textbook of Influenza, 2nd Edition, Blackwell, Oxford, 2004, in press. [2] T. Ito, et al., Molecular basis for the generation in pigs of influenza A viruses with pandemic potential, J. Virol. 72 (1998) 7367 – 7373. [3] T. Ito, Interspecies transmission and receptor recognition of influenza A viruses, Microbiol. Immunol. 44 (2000) 423 – 430. [4] R.J. Webby, R.G. Webster, Emergence of influenza A viruses, Philos. Trans. R. Soc. Lond., Biol. Sci. 356 (2001) 1817 – 1828. [5] R.G. Webster, et al., Evolution and ecology of influenza A viruses, Microbiol. Rev. 56 (1992) 152 – 179. [6] C.W. Olsen, The emergence of novel swine influenza viruses in North America, Virus Res. 85 (2002) 199 – 210. [7] C.W. Olsen, Emergence of novel strains of swine influenza virus in North America, in: A. Morilla, K.-J. Yoon, J.J. Zimmerman (Eds.), Trends in Emerging Viral Infections of Swine, Iowa State University Press, Ames, 2002, pp. 37 – 43. [8] T.M. Chambers, et al., Influenza viral infection of swine in the United States 1988 – 1989, Arch. Virol. 116 (1991) 261 – 265. [9] V.S. Hinshaw, et al., The prevalence of influenza viruses in swine and the antigenic and genetic relatedness of influenza viruses from man and swine, Virology 84 (1978) 51 – 62. [10] C.W. Olsen, et al., Virologic and serologic surveillance for human, swine and avian influenza virus infections among pigs in the north-central United States, Arch. Virol. 145 (2000) 1399 – 1419. [11] N.N. Zhou, et al., Genetic reassortment of avian, swine, and human influenza A viruses in American pigs, J. Virol. 73 (1999) 8851 – 8856. [12] A.I. Karasin, et al., Genetic characterization of H3N2 influenza viruses isolated from pigs in North America, 1977 – 1999: evidence for wholly human and reassortant virus genotypes, Virus Res. 68 (2000) 71 – 85. [13] R.J. Webby, et al., Evolution of swine H3N2 influenza viruses in the United States, J. Virol. 74 (2000) 8243 – 8251. [14] G.A. Landolt, et al., Comparison of the pathogenesis of two genetically different H3N2 influenza A viruses in pigs, J. Clin. Microbiol. 41 (2003) 1936 – 1941. [15] A.I. Karasin, G.A. Anderson, C.W. Olsen, Genetic characterization of an H1N2 influenza virus isolated from a pig in Indiana, J. Clin. Microbiol. 38 (2000) 2453 – 2456.
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[16] A.I. Karasin, et al., Genetic characterization of H1N2 influenza A viruses isolated from pigs throughout the United States, J. Clin. Microbiol. 40 (2002) 1073 – 1079. [17] Y.K. Choi, S.M. Goyal, H.S. Joo, Prevalence of swine influenza virus subtypes on swine farms in the United States, Arch. Virol. 147 (2002) 1209 – 1220. [18] Y.K. Choi, et al., Phylogenetic analysis of H1N2 isolates of influenza A virus from pigs in the United States, Virus Res. 87 (2002) 173 – 179. [19] C.W. Olsen, A. Karasin, G. Erickson, Characterization of a swine-like reassortant H1N2 influenza virus isolated from a wild duck in the United States, Virus Res. 93 (2003) 115 – 121. [20] D.L. Suarez, et al., Isolation from turkey breeder hens of a reassortant H1N2 influenza virus with swine, human, and avian lineage genes, Avian Dis. 46 (2002) 111 – 121. [21] L. Cooper, et al., Molecular characterization of influenza A viruses bearing swine-like heamgglutinin genes isolated from humans, Abstracts of the Virus Evolution Workshop, Ardmore, OK, 1999, http:// www.noble.org/virusevolution/abstracts/Cooperpost.htm. [22] R.J. Webby, et al., Increased genetic diversity of swine influenza in the United States, Scientific Programs and Abstracts, American Society for Virology 21st Annual Meeting, 2002, p. 57. [23] A.I. Karasin, et al., Isolation and characterization of H4N6 avian influenza viruses from pigs with pneumonia in Canada, J. Virol. 74 (2000) 9322 – 9327.
www.ics-elsevier.com
The emergence of novel influenza viruses among pigs in North America due to interspecies transmission and reassortment Christopher W. Olsen *, Gabriele A. Landolt, Alexander I. Karasin Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53717, USA
Abstract. In 1997 – 1998, H3N2 influenza viruses of different genotypes emerged among North American pigs. Triple reassortant H3N2 viruses containing human, classical swine and avian virus genes spread widely within the swine population and gave rise subsequently to reassortant H1N2 and H1N1 viruses. Together with wholly avian viruses recovered from North American pigs since 1999, these viruses emphasize that influenza virus interspecies transmission and reassortment in pigs can occur throughout world. They provide important research tools with which the genetic factors that control interspecies transmission can be investigated. D 2003 Elsevier B.V. All rights reserved. Keywords: Influenza; Swine; Reassortment; Interspecies transmission; Pandemic
1. Introduction Influenza virus infection in pigs is a cause of economically important respiratory disease in the animals and a human public health concern. Influenza viruses are transmitted from pigs to people as zoonotic agents (reviewed in Ref. [1]) and pigs can serve as hosts for influenza virus reassortment, thus potentially contributing to the creation of pandemic viruses (reviewed in Refs. [2,3]). Southeast Asia has historically been described as an ‘‘epicenter’’ for pandemic viruses (reviewed in Refs. [4,5]), but the viruses that have appeared recently within the swine population of North America (reviewed in Refs. [6,7]) demonstrate that interspecies transmission and reassortment of influenza viruses in pigs can occur anywhere in the world. 2. Emergence of H3N2 influenza viruses among North American pigs Swine influenza in the United States was caused almost exclusively by the ‘‘classical’’ H1N1 swine viruses from the time of their first isolation in 1930 through the mid-1990s * Corresponding author. Tel.: +1-608-265-8681; fax: +1-608-263-0438. E-mail address: [email protected] (C.W. Olsen). 0531-5131/ D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.02.145
C.W. Olsen et al. / International Congress Series 1263 (2004) 196–199
197
Table 1 Genotypes of the predominant H1N1, H3N2 and H1N2 viruses circulating among American pigs, 1998 – 2003 Gene segment
Classical swine H1N1 viruses
Reassortant H3N2 viruses
Reassortant H1N2 viruses
Reassortant H1N1 viruses
PB2 PB1 PA HA NP NA M NS
swine swine swine swine swine swine swine swine
avian human avian human swine human swine swine
avian human avian swine swine human swine swine
avian human avian swine swine swine swine swine
[8,9]. In 1997– 1998, however, H3N2 viruses appeared among North American pigs [10 – 12]. Genetic analyses of an initial group of nine isolates revealed that 3 different genotypes of H3N2 viruses had emerged independent of one another: a wholly human virus [12]; a reassortant virus containing human and classical swine virus genes [11]; and ‘‘triple reassortant’’ viruses containing genes from human, classical swine and avian viruses [11,12]. Of these, only the triple reassortant viruses have been maintained in the population (Table 1). These are now endemic throughout the American swine population [13] (Olsen et al., unpublished surveillance data). In fact, the wholly human isolate has been shown experimentally to be inherently restricted in its ability to infect pigs [14] and primary swine respiratory epithelial cells (Landolt et al., in preparation), compared with a prototypical triple reassortant virus. 3. Emergence of second generation reassortant H1N2 and H1N1 viruses After 1998, both the triple reassortant H3N2 and classical swine H1N1 viruses cocirculated among American pigs, and both subtypes have been isolated from single swine samples (Olsen et al., unpublished data). Therefore, it is not surprising that additional reassortant genotypes of viruses have also appeared. The first to be recognized were H1N2 viruses that had the ‘‘genetic backbone’’ of the triple reassortant H3N2 viruses, but had acquired an H1 HA gene from a classical swine virus (Table 1) [15]. These H1N2 viruses have become endemic throughout the American swine population [16 –18], and have also been isolated from wild waterfowl [19] and domestic turkeys [20]. Reassortment between the triple reassortant H3N2 (or H1N2) viruses and classical swine H1N1 viruses also created H1N1 viruses containing the human/swine/avian genetic backbone of the reassortant H3N2 and H1N2 viruses, but with both H1 HA and N1 neuraminidase genes from a classical swine virus (Table 1). Interestingly, these reassortant H1N1 viruses were first recognized in a human being [21], but were isolated subsequently from pigs [22]. Our surveillance data (Olsen et al., unpublished data) indicate that they are becoming the predominant form of H1N1 virus isolated from American pigs. 4. Isolation of wholly avian viruses from North American pigs Wholly avian viruses have been isolated from pigs in Canada on three occasions since 1999. These include H1N1 and H3N3 viruses (Olsen et al., in preparation), as well as
198
C.W. Olsen et al. / International Congress Series 1263 (2004) 196–199
H4N6 viruses [23]. Of these, the H4N6 viruses isolated from pigs on a farm in Ontario in 1999 are of particular interest because this is a subtype to which the human population is immunologically naı¨ve and, in the course of moving from waterfowl to pigs, this virus had already acquired signature sequences consistent with an ability to utilize the a2,6-linked sialic acid receptors expressed by human respiratory airway cells [23]. Acknowledgements This work was supported by grants from the USDA NRICGP and the University of Wisconsin-Madison School of Veterinary Medicine. The authors thank the following colleagues for providing virus isolates, reagents and/or expertise: Nancy Cox, Lynnette Brammer, Lynn Cooper, Henrietta Hall, Jackie Katz, Alexander Klimov, Catherine Smith, Kanta Subbarao, Sabrina Swenson, John Landgraf, Beverly Schmitt, Dennis Senne, Ian Brown, Suzanne Carman, Keith West, Gary Anderson, Sagar Goyal, Mary Woodruff, Gail Scherba, Gene Erickson, Yoshihiro Kawaoka, James Gern, Rebecca Brockman-Schneider, Gabriele Neumann, Lynette Phillips, Peter Shult, Carol Kirk, Yasou Suzuki and Takashi Suzuki. References [1] C.W. Olsen, Influenza in pigs and their role as the intermediate host, in: K.G. Nicholson, R.G. Webster, A. Hay, N.J. Cox (Eds.), Textbook of Influenza, 2nd Edition, Blackwell, Oxford, 2004, in press. [2] T. Ito, et al., Molecular basis for the generation in pigs of influenza A viruses with pandemic potential, J. Virol. 72 (1998) 7367 – 7373. [3] T. Ito, Interspecies transmission and receptor recognition of influenza A viruses, Microbiol. Immunol. 44 (2000) 423 – 430. [4] R.J. Webby, R.G. Webster, Emergence of influenza A viruses, Philos. Trans. R. Soc. Lond., Biol. Sci. 356 (2001) 1817 – 1828. [5] R.G. Webster, et al., Evolution and ecology of influenza A viruses, Microbiol. Rev. 56 (1992) 152 – 179. [6] C.W. Olsen, The emergence of novel swine influenza viruses in North America, Virus Res. 85 (2002) 199 – 210. [7] C.W. Olsen, Emergence of novel strains of swine influenza virus in North America, in: A. Morilla, K.-J. Yoon, J.J. Zimmerman (Eds.), Trends in Emerging Viral Infections of Swine, Iowa State University Press, Ames, 2002, pp. 37 – 43. [8] T.M. Chambers, et al., Influenza viral infection of swine in the United States 1988 – 1989, Arch. Virol. 116 (1991) 261 – 265. [9] V.S. Hinshaw, et al., The prevalence of influenza viruses in swine and the antigenic and genetic relatedness of influenza viruses from man and swine, Virology 84 (1978) 51 – 62. [10] C.W. Olsen, et al., Virologic and serologic surveillance for human, swine and avian influenza virus infections among pigs in the north-central United States, Arch. Virol. 145 (2000) 1399 – 1419. [11] N.N. Zhou, et al., Genetic reassortment of avian, swine, and human influenza A viruses in American pigs, J. Virol. 73 (1999) 8851 – 8856. [12] A.I. Karasin, et al., Genetic characterization of H3N2 influenza viruses isolated from pigs in North America, 1977 – 1999: evidence for wholly human and reassortant virus genotypes, Virus Res. 68 (2000) 71 – 85. [13] R.J. Webby, et al., Evolution of swine H3N2 influenza viruses in the United States, J. Virol. 74 (2000) 8243 – 8251. [14] G.A. Landolt, et al., Comparison of the pathogenesis of two genetically different H3N2 influenza A viruses in pigs, J. Clin. Microbiol. 41 (2003) 1936 – 1941. [15] A.I. Karasin, G.A. Anderson, C.W. Olsen, Genetic characterization of an H1N2 influenza virus isolated from a pig in Indiana, J. Clin. Microbiol. 38 (2000) 2453 – 2456.
C.W. Olsen et al. / International Congress Series 1263 (2004) 196–199
199
[16] A.I. Karasin, et al., Genetic characterization of H1N2 influenza A viruses isolated from pigs throughout the United States, J. Clin. Microbiol. 40 (2002) 1073 – 1079. [17] Y.K. Choi, S.M. Goyal, H.S. Joo, Prevalence of swine influenza virus subtypes on swine farms in the United States, Arch. Virol. 147 (2002) 1209 – 1220. [18] Y.K. Choi, et al., Phylogenetic analysis of H1N2 isolates of influenza A virus from pigs in the United States, Virus Res. 87 (2002) 173 – 179. [19] C.W. Olsen, A. Karasin, G. Erickson, Characterization of a swine-like reassortant H1N2 influenza virus isolated from a wild duck in the United States, Virus Res. 93 (2003) 115 – 121. [20] D.L. Suarez, et al., Isolation from turkey breeder hens of a reassortant H1N2 influenza virus with swine, human, and avian lineage genes, Avian Dis. 46 (2002) 111 – 121. [21] L. Cooper, et al., Molecular characterization of influenza A viruses bearing swine-like heamgglutinin genes isolated from humans, Abstracts of the Virus Evolution Workshop, Ardmore, OK, 1999, http:// www.noble.org/virusevolution/abstracts/Cooperpost.htm. [22] R.J. Webby, et al., Increased genetic diversity of swine influenza in the United States, Scientific Programs and Abstracts, American Society for Virology 21st Annual Meeting, 2002, p. 57. [23] A.I. Karasin, et al., Isolation and characterization of H4N6 avian influenza viruses from pigs with pneumonia in Canada, J. Virol. 74 (2000) 9322 – 9327.