1. Introduction
Influenza viruses are the members of Orthomyxoviridae family and have a wide host range [1,2,3,4,5,6]. Due to unique physiology, swine are considered the “mixing vessel” for influenza viruses [7]. Four types of influenza viruses have been reported in swine i.e., influenza A virus (IAV), influenza B virus (IBV), influenza C virus (ICV), and influenza D virus (IDV). The genomes of IAV and IBV have eight gene segments of single-stranded negative sense RNA while the genomes of ICV and IDV have seven gene segments [8]. Among the eight gene segments of IAV and IBV, the hemagglutinin (HA) and neuraminidase (NA) are most significant and crucial for the pathogenicity of these viruses which determine the antigenic properties. The HA gene regulates the attachment of virus particles to the host receptor while NA gene regulates the release of progeny virus into the host cell. Co-infection of swine with two or more IAV strains may trigger the reassortment [9] which in turn, could facilitate the emergence of new influenza virus strains [10,11,12]. Point mutations which occur due to an error-prone RNA polymerase that lacks the ability of proof-reading and corrections during replication may also complement the genetic diversity of the influenza viruses [13]. The mechanisms of reassortment and point mutations may give rise to “antigenic shift” and “antigenic drift” within HA and NA genes, respectively, facilitating the emergence of new subtypes and lineages of influenza viruses. As a result, total 18 HA and 11 NA subtypes of IAV [14,15,16] and two lineages (Victoria/B and Yamagata/B) of IBV have been reported so far in different hosts [17,18].
The host range of IAV and IBV is determined by their specificity to sialic acid receptors. The HA proteins of IAV can bind to α-2,3 and α-2,6 sialic acid receptors present in avian and human trachea, respectively [19,20,21]. Interestingly, swine trachea has both, α-2,3 as well as α-2,6 sialic acid receptors, due to which swine can become infected with avian and human strains of influenza viruses [22].
The genomes of ICV and IDV have a gene segment termed as “hemagglutinin–esterase-fusion” (HEF) which carries out the functions similar to that of HA and NA genes of IAV and IBV. The HEF is responsible for attachment and release of ICV and IDV virus particles into the host cell [23,24,25]. The particles of both virus types ICV and IDV bind to 9-O-acetylated sialic acid receptors of the host [25]. Several studies have shown that human and avian origin influenza viruses can be transmitted to swine in natural settings and thus may evolve into new strains of reassorted influenza viruses [26,27].
Historically, the first flu pandemic (Spanish flu) hit the human population in 1918 [28] and killed approximately 50 million people globally [29]. The 1918 influenza pandemic emerged as a result of reassortment in which human H1 virus acquired avian (poultry) N1 neuraminidase along with internal protein genes and evolved into what is now termed as “classical H1N1” virus [30] (Figure 1).
The second flu pandemic occurred in 1957 (Asian flu) and was traced to the H2N2 virus which killed approximately two million people [31]. The third flu pandemic hit the human population in 1968 (Hong Kong flu) with an H3N2 outbreak and killed approximately two million people [31,32]. The most recent flu pandemic (Swine flu) originated in swine in Mexico during March–May 2009 [33] and killed approximately 575,000 people worldwide [31]. The swine flu occurred due to a pandemic reassortant H1N1 virus termed as “A(H1N1)pdm09” virus [33].
Among four types of the influenza viruses, IAV is the most prevalent type and has been reported in swine in several countries. The IAV was first isolated from the nasal discharge of a swine in 1931 [34] and from the human in 1933 [35]. Strains of IAV have been reported to cause mild to severe upper respiratory tract illness in swine [36]. Strains of Victoria/B and Yamagata/B lineages of IBV were first reported in swine in the United States in 2010 [37] while the ICV in swine was first isolated in China in 1983 [38]. Both, the IBV and ICV cause mild respiratory illness in swine [39,40,41,42]. The IDV in swine was first detected in Oklahoma based swine in the United States in 2011 [5,43] which in later years has been detected in swine in China [44], Italy [45] and Luxembourg [46]. Interestingly, influenza viruses can be detected in the swine throughout the year unlike humans where seasonality affects the occurrence and progression of the disease [47,48].
An active surveillance of influenza viruses in swine is necessary for two basic reasons; to track the influenza virus evolution for improvements of the currently available diagnostic tests as well as for generating more effective vaccines for prevention and control of disease [49]. The currently available scientific data on swine influenza viruses would serve as a key to understand their evolutionary dynamics and transmission patterns. Therefore, this systematic review, for the first time, summarizes all four types of influenza viruses in the swine populations worldwide.