2.1 Porcine Circovirus 2

Porcine Circovirus 2 (PCV2), is a small non-enveloped DNA virus which contains a single-stranded circular genome of 1.7 kb belonging to the family of circoviridae (Hamel, Lin, & Nayar, 1998; Meehan et al., 1998), this virus contributes to the considerable economic losses associated with PCV2-associated disease (PCVAD/PCVD)(Chae, 2005). The most prevalent symptoms of PCVAD/PCVD include porcine dermatitis and nephropathy syndrome (PDNS), which mainly occurs during the growing or finishing stage of pigs (Segales, 2012). According to the different of Cap gene sequence, PCV2 can be divided into several subtypes, PCV 2a-h (Bao et al., 2018; Franzo & Segales, 2018; Yao et al., 2019), the PCV 2a and PCV 2b which are considered to be the most prevalent genotype (Patterson & Opriessnig, 2010; Segales et al., 2008). It has been reported that, PCV2 is crucial but not a sole factor to develop this clinical disease, it must co-infect with other pathogens in order to cause this disease(Tomas, Fernandes, Valero, & Segales, 2008).
Mhp and PCV2 are the major pathogens that cause significant financial loss (Tassis et al., 2017), coincidental infection of Mhp and PCV2 is ubiquitous in clinical conditions and contributes to a range of polymicrobial disease syndromes, such as porcine respiratory disease complex (PRDC) and PMWS (Chae, 2005; Krakowka et al., 2007; Segales, 2012). The co-infection rate of Mhp and PCV2 has been reported to be 35.5% (172/484) in US field cases (Pallares et al., 2002). Fablet and colleagues found that, the detection rate of Mhp DNA in a pig was 33.6% which meant that the PCV2 genome load in sera were 4.3104 copies/mL (Fablet, Marois-Crehan, et al., 2012). The pigs’ lymph nodes were tumefied compared to the normal size, with their lungs having some cranioventral dark purple consolidation, and accompanied by shedding of high levels of PCV2 DNA in semen in coinfection with Mhp and PCV2 cases (Opriessnig, Madson, et al., 2011). Other group also demonstrated, the severity of PCV2-associated lesions in lung and lymphoid tissues of pigs, with a number of antigens within these lesions being significantly higher compared to the control group (Opriessnig et al., 2004).
Both PCV2 and Mhp can target host immune cells and impair host defenses, resulting in a significant increase in the expression of Interferon-gamma (IFN-γ), Interleukin-1beta (IL-1β), IL-8, Chemokine (C-C motif) ligand 5 (CCL5) and Chemokine (CXC motif) ligand 10 (CXCL10), weak stimulation of IFN-β, IL-6 and IL-10 and downregulated of IL-13 and IFN-α significantly (H. R. Zhang, Lunney, Baker, & Opriessnig, 2011). Furthermore, Mhp enhanced the levels of PCV2 viraemia, whereas PCV2 did not enhance the levels of mycoplasmal nasal shedding in co-infected pigs, compared to singly Mhp or PCV2-infected pigs (Seo, Park, Park, & Chae, 2014). PCV2 replication could be enhanced by subsequent inoculation with Mhp, however, simultaneous PCV2 and Mhp co-inoculation does not potentiate disease in conventional pigs (Sibila, Fort, Nofrarias, Perez de Rozas, et al., 2012; Wang et al., 2016). Other researchers also indicated that, concurrent infection with PCV2 and Mhp did not result in potentiation of clinical signs and lesions attributed to either infection in conventional pigs (Sibila, Fort, Nofrarias, de Rozas, et al., 2012). These results indicated that synergistic effects occur during the process of Mhp and PCV2 sequential infection, and some previous studies also demonstrated that Mhp infection in pigs normally occurs slightly before or around PCV2 infection in the field condition (Chae, 2012; Fachinger, Bischoff, Jedidia, Saalmuller, & Elbers, 2008; Larochelle, Magar, & D’Allaire, 2003). Therefore, the study of the interaction between Mhp and PCV2 co-infection based on sequential infection model may be closer to the field condition in pig industry.