2.2 Porcine Reproductive and Respiratory Syndrome Virus

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), is an enveloped, single-stranded, positive sense RNA virus in the family ofArteriviridae (Kavanova et al., 2018) and an etiologic agent that causes porcine reproductive and respiratory syndrome (PRRS), which has been estimated to be the cause of a lost $600 million in the US swine industry at least every year (Neumann et al., 2005). The typical symptoms of PRRSV are characterized by blue-ear and failure in pregnant pigs (Lunney et al., 2016), also these infections can induce cell lysis, apoptosis, changes in T-cell subpopulations etc (Labarque, Van Gucht, Nauwynck, Van Reeth, & Pensaert, 2003; Shimizu et al., 1996; Thanawongnuwech, Thacker, & Halbur, 1997).
It has been reported that, the concurrent infection with Mhp and PRRSV is common (Chae, 2016; Fablet, Marois-Crehan, Grasland, Simon, & Rose, 2016b; Pallares et al., 2002). Scott and colleagues have proved their hypothesis that PRRSV and Mhp can be transported via airborne route (Dee, Otake, Oliveira, & Deen, 2009; Otake, Dee, Corzo, Oliveira, & Deen, 2010), these characteristics of pathogens increased the difficulty to control these diseases. PRRSV replicates mainly in porcine alveolar macrophages (PAMs), dendritic cells (DC) in lungs and the upper respiratory tract (Lunney et al., 2016), resulting in viremia as early as 12 h post infection at the early infection stage(Wills, Doster, Galeota, Sur, & Osorio, 2003). For the persistence period, viral replication is primarily localized in lymphoid organs, including tonsil and lymph nodes but not spleen (Allende et al., 2000; Rowland, Lawson, Rossow, & Benfield, 2003; Wills et al., 1997) and gradual decays until the virus becomes extinct in the host (Christopher-Hennings, Nelson, Althouse, & Lunney, 2008; Wills et al., 2003).
The PAMs from pigs infected with PRRSV have significantly downregulated the ability to kill bacteria (Solano, Bautista, Molitor, Segales, & Pijoan, 1998). Although, some researchers have demonstrated that co-infection with Mhp and PRRSV show no potentiating effect (Van Alstine, Stevenson, & Kanitz, 1996). Thacker and colleagues suggested that the Mhp potentiated and prolonged PRRSV-induced pneumonia clinically, macroscopically and microscopically regardless of the inoculation sequence of infection to both pathogens, whereas PRRSV did not aggravate Mhp infection in piglets when inoculated before Mhp under experimental conditions (Thacker, Halbur, Ross, Thanawongnuwech, & Thacker, 1999; Tzika et al., 2015; Van Alstine et al., 1996). Furthermore, Fablet suggested that, the infection by Mhp was associated with PRRSV seropositive status (Fablet, Marois-Crehan, Grasland, Simon, & Rose, 2016a). Moreover, in the concurrent infection with Mhp and PRRSV, many vital functional genes were detected as being differentially expressed (DE) in PAMs (Li et al., 2015), especially, IL-1β was considerably higher, which is a key component for downstream signal pathways. In addition, the co-infection of Mhp and PRRSV significantly increased the severity and duration of pneumonia in experimentally infected pigs, which was associated with induction of several proinflammatory cytokines (Thacker, Thacker, Kuhn, Hawkins, & Waters, 2000), such as IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12 and Tumor Necrosis Factor-alpha (TNF-α) (Thanawongnuwech, Thacker, Halbur, & Thacker, 2004; Thanawongnuwech & Thacker, 2003; Thanawongnuwech, Young, Thacker, & Thacker, 2001). Other group also found increased levels of both IL-12 and IL-10 in the respiratory tract of pigs experimentally infected with either Mhp and/or PRRSV, IFN-γ and Insulin-like Growth Factor-I (IGF-I) production were lower and delayed in pigs co-infected with PRRSV and Mhp(Roberts & Almond, 2003; Thanawongnuwech & Thacker, 2003). These results suggest that the exacerbation Mhp respiratory disease may be due to viral infection which induces regulatory T cells (Tregs) (LeRoith et al., 2011). In contrast, Fano et al suggested that Mhp did not affect these epidemiological features of PRRSV-associated disease under the conditions of study (Fano, Pijoan, & Dee, 2007).
Other studies also implicated that a single-dose vaccination against Mhp alone decreased the levels of PRRSV viremia and PRRSV-associated pulmonary lesions, whereas single-dose vaccination against PRRSV alone did not decrease nasal shedding of Mhp and Mhp-associated pulmonary lesions in the co-infected pigs (S. J. Park, Seo, Park, & Chae, 2014). Combining vaccines with Mhp and PRRSV did not induce negative interaction which would reduce the efficacy of each individual vaccine (Bourry, Fablet, Simon, & Marois-Crehan, 2015). These results indicated that, the combined vaccination is more efficient than single ones, consequently, further research should focus on the developing of combined vaccine, which can improve the convenient and efficient pig production simultaneously.