Elsevier

Virus Research

Volume 85, Issue 2, 10 May 2002, Pages 199-210
Virus Research

Review
The emergence of novel swine influenza viruses in North America

https://doi.org/10.1016/S0168-1702(02)00027-8Get rights and content

Abstract

Since 1997, novel viruses of three different subtypes and five different genotypes have emerged as agents of influenza among pigs in North America. The appearance of these viruses is remarkable because there were no substantial changes in the overall epidemiology of swine influenza in the United States and Canada for over 60 years prior to this time. Viruses of the classical H1N1 lineage were virtually the exclusive cause of swine influenza from the time of their initial isolation in 1930 through 1998. Antigenic drift variants of these H1N1 viruses were isolated in 1991–1998, but a much more dramatic antigenic shift occurred with the emergence of H3N2 viruses in 1997–1998. In particular, H3N2 viruses with genes derived from human, swine and avian viruses have become a major cause of swine influenza in North America. In addition, H1N2 viruses that resulted from reassortment between the triple reassortant H3N2 viruses and classical H1N1 swine viruses have been isolated subsequently from pigs in at least six states. Finally, avian H4N6 viruses crossed the species barrier to infect pigs in Canada in 1999. Fortunately, these H4N6 viruses have not been isolated beyond their initial farm of origin. If these viruses spread more widely, they will represent another antigenic shift for our swine population, and could pose a threat to the world's human population. Research on these novel viruses may offer important clues to the genetic basis for interspecies transmission of influenza viruses.

Introduction

Influenza was first recognized clinically in pigs during the late summer and fall of 1918 in the midwestern United States (Koen, 1919, Easterday and Hinshaw, 1992), coincident with the dramatic and devastating human influenza pandemic that killed 20–40 million people around the world (Murphy and Webster, 1996). The first swine influenza viruses were isolated from pigs in 1930 (Shope, 1931). These were the progenitors of what is now recognized as the ‘classical’ H1N1 lineage of swine influenza A viruses. Influenza A viruses of other subtypes have been isolated relatively commonly from pigs elsewhere in the world, including H3N2 viruses (Sugimura et al., 1980, Nakajima et al., 1982, Ottis et al., 1982, Yasuhara et al., 1983, Mancini et al., 1985, Castrucci et al., 1994, Campitelli et al., 1997) and H1N2 viruses (Nerome et al., 1985, Gourreau et al., 1994, Brown et al., 1995, Brown et al., 1998, Ouchi et al., 1996, Ito et al., 1998b, VanReeth et al., 2000). In addition, avian H1N1 viruses have been isolated from pigs in Europe and Asia (Pensaert et al., 1981, Schultz et al., 1991, Brown et al., 1993, Brown et al., 1997, Guan et al., 1996). However, from 1930 through the mid-1990s, influenza in North American pigs was caused almost exclusively by infection with classical H1N1 swine viruses. Serosurvey studies conducted in the United States in 1976–1977 (Hinshaw et al., 1978), 1988–1989 (Chambers et al., 1991) and 1997–1998 (Olsen et al., 2000) revealed high rates of seropositivity among pigs to classical H1 swine influenza viruses (28–51%), but much lower seroprevalence rates against H3 viruses. In fact, in the 1976–1977 (Hinshaw et al., 1978) and 1988–1989 (Chambers et al., 1991) studies, only approximately 1% of pigs had antibodies against H3 viruses, and prior to 1997, only three H3 viruses had been isolated from pigs in North America (Hinshaw et al., 1978, Bikour et al., 1994, Bikour et al., 1995). However, a dramatic shift in the epidemiologic pattern of swine influenza began in 1997–1998. The 1997–1998 serosurvey (Olsen et al., 2000) detected an unexpected and substantial increase in H3 seropositivity (8%), and H3N2 viruses began to be isolated from pigs in both the US and Canada during this time (Karasin et al., 2000c, Zhou et al., 1999). Subsequently, reassortment between H3N2 viruses and classical H1N1 swine viruses led to the appearance of second generation H1N2 reassortant viruses (Karasin et al., 2000a, Karasin et al., 2002). In addition, avian H4N6 viruses of duck origin have been isolated from pigs in Canada (Karasin et al., 2000b). This review summarizes what is known about these novel viruses, as well as recently described antigenic drift variants of classical H1N1 swine influenza viruses (Dea et al., 1992, Olsen et al., 1993, Olsen et al., 2000, Rekik et al., 1994), and discusses the potential veterinary and human public health implications of these viruses.

Section snippets

Background

Influenza A viruses are enveloped, negative-sense RNA viruses that encode 10 major viral proteins on eight independent segments of RNA. The hemagglutinin (HA or H) is a large N-linked glycoprotein that projects as trimers from the viral envelope. The HA binds to sialic acid-containing receptors and mediates infection of host cells and cell-to-cell fusion following proteolytic cleavage of the HA into HA1 and HA2 segments (Lamb and Krug, 1996). The HA1 forms the large globular head of the protein

Variants of classical H1N1 swine influenza viruses

Research by Sheerar et al., 1989, Luoh et al., 1992 and Noble et al. (1993) demonstrated that the classical H1N1 swine influenza viruses in the United States remained antigenically and genetically highly conserved from 1965 through the 1980s. In fact, the rate of drift in the HA1 segments for swine viruses was 0.4–0.48% amino acid changes/year (Luoh et al., 1992), compared with a rate of 0.8% for human H1N1 viruses (Raymond et al., 1983). More recently, however, a number of antigenic and

The emergence of H3N2 influenza viruses among pigs in North America

The role that pigs play as the mixing vessel hosts for genetic reassortment among human and avian influenza viruses and the development of new pandemic human influenza viruses is well recognized. In addition, it is clear that swine influenza viruses can be transmitted to people as zoonotic agents (Smith et al., 1976, Top and Russell, 1977, Hinshaw et al., 1978, Eason and Sage, 1980, Dasco et al., 1984, Patriarca et al., 1984, de Jong et al., 1988, Rota et al., 1989, Wentworth et al., 1994,

H1N2 influenza viruses in pigs in the United States

In November 1999, influenza-like respiratory illness, as well as abortions in sows, occurred among pigs on a farm in Indiana. An influenza virus isolated from lung tissue of a sow that died during the outbreak was shown by HI and neuraminidase-inhibition (NI) antigenic assays and genetic analyses to be an H1N2 subtype virus (Karasin et al., 2000a). Further sequencing and phylogenetic analyses revealed that this was a second generation reassortant virus with NA, PB1, M, NP, NS, PA and PB2 genes

Interspecies transmission of avian H4N6 influenza viruses to pigs in Canada

Since the respiratory tracts of pigs contain both α2,3 and α2,6 sialic acid receptors (Ito et al., 1998a), the species barrier to transmission of avian influenza viruses is relatively less stringent for pigs than for people. Kida et al. (1994) has demonstrated that pigs can be experimentally infected by a wide variety of subtypes of avian influenza viruses. Nonetheless, relatively few examples of natural infection of pigs with wholly avian influenza viruses have been documented. The most

Summary

The epidemiology of influenza among pigs in North America has changed dramatically since 1997. Viruses of H3N2, H1N2 and H4N6 subtypes have been isolated from pigs after a period of over 60 years in which swine influenza was caused almost exclusively by infection with H1N1 viruses. The H3N2 and H1N2 viruses appear to have become widely established within the swine population of the United States. Beyond traditional antigenic typing, extensive genetic analyses have been conducted in order to

Acknowledgments

This work was supported in part by grants from the USDA NRICGP and the University of Wisconsin School of Veterinary Medicine Food Animal Grant program. The author thanks Alexander Karasin (University of Wisconsin-Madison) for excellent technical assistance, Yoshihiro Kawaoka and Gabrielle Landolt (University of Wisconsin-Madison) for helpful discussions, and collaborators from the Centers for Disease Control and Prevention (Nancy Cox, Catherine Smith, Kanta Subbarao, Lynn Cooper), the

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