Five key aspects of the immune response against PRRS virus infection in swine

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Five key aspects of the immune response against PRRS virus infection in swine

Although the porcine reproductive and respiratory syndrome caused by PRRS virus was recognized over 20 years ago, some fundamental aspects of the immune response triggered after infection have not yet been elucidated.

It seems clear that PRRS virus suppresses innate immunity, however the interactions between innate and adaptive immune responses still need to be elucidated:

One of the main limitations of the studies of PRRS virus infection in pigs at the cellular and molecular level, that partly explains the lack of basic knowledge of the immune response to PRRS virus, is the inability to establish a mouse model of infection, due to the fact that PRRS virus replication in common laboratory rodent species is inefficient1. On the other hand, infection with PRRS virus is widespread in the swine population, making it difficult to find uninfected animals with which to perform experiments aimed at investigating how the virus affects the immune system of the pig. Furthermore, pigs reared under conventional conditions are usually colonized by microorganisms that may eventually cause disease during an experimental infection as a result of the effect of PRRS virus on the immune system, thus invalidating the conclusions of the study.

Despite the above, some important aspects of the immune response developed by pigs to PRRS virus have been described, allowing an understanding of the behavior of the infection in vivo.

  • PRRS virus infects cells that have regulatory control: Unlike the influenza virus, which infects the respiratory tract and lungs of pigs, causing lesions as a direct result of its cytolytic effect on the epithelium, PRRS virus not only infects cells of the lung, causing pneumonia, but also infects cells of hematopoietic and lymphoid tissues. This triggers another type of disease mechanism and clinical manifestations, as a consequence of immune dysregulation. 
     
  • PRRS virus interferes with interferon induction: Interferons (INFs) are cytokines of primary importance in the innate immune response to virus infections. Expression of IFNs is induced upon recognition of viral molecular patterns by cellular cytoplasmic and endosomal receptors, or by cytokines such as IL-12. Based on the type of receptor through which they signal, interferons have been classified into types I, II and III, all being antiviral agents and immune modulators. It has been demonstrated that PRRS virus inhibits the synthesis of type I IFN-α in pigs2. IFN-α, like other type I IFNs, activates molecules which prevent the virus from producing and replicating its RNA. PRRS virus also fails to induce porcine plasmacytoid dendritic cells to produce IFN-α in vivo. Finally, the PRRS virus non–structural proteins Nsp1, Nsp2, and Nsp11, and the structural protein N (nucleocapsid protein) have been found to be antagonists of IFN induction.
     
  • PRRS virus fails to develop sterilizing immunity: Although anti-PRRS virus antibodies can be detected as early as 1 week after infection, and viral neutralizing antibodies (VNab) are detected at 4 weeks after infection, viremia can persist even in the presence of VNab, and can even be resolved before VNab appear. As a consequence, PRRSV infections are not resolved rapidly in piglets, and the carrier state may exist for up to 150 days. Nevertheless, the VNab are considered to be important in protecting swine against PRRS virus infection, although their mechanism of action has not yet been described. 
     
  • Different PRRS virus strains show differences in immune dysregulation: It is well known that PRRS viruses displays great genetic variability . Apart from the two major genotypes (types I and II),several subtypes and lineages with varying pathogenicity and biological characteristics have been described. It has been shown that PRRSV field isolates have a variable suppressive effect on IFN-α induction in PAM cultures. A2MC2, which is a novel PRRS virus strain, resulted in a higher level of neutralizing antibody after infection than an MLV vaccine strain that is highly homologous in sequence.

  • PRRS virus affects both innate and adaptive immunity: It is known that PRRS virus is able to infect both the fetus in utero and the newborn piglet. This early infection interferes with innate immunity, by altering the function of immune subsets of cells and the induction of IFN. This not only inhibits the early host defense, but also alters the development of adaptive immunity in the grower? (growing? fattening?) pig. Besides this, the immune system of the young piglet is immature compared to the adult pig. When young, the piglet depends primarily on innate immunity and antibodies received during lactation (Figure 1). If the piglet cannot properly develop adaptive immunity as a consequence of PRRS virus infection, the infection is not controlled and the disease is more severe. 

References:

1. Rosenfeld, Paul et al., Evaluation of Porcine Reproductive and Respiratory Syndrome Virus Replication in Laboratory Rodents. Can J Vet Res. 2009. 73: 313–318.
2. Buddaert W, et al ., In vivo and in vitro interferon (IFN) studies with the porcine reproductive and respiratory syndrome virus (PRRSV). Adv Exp Med Biol. 1998. 440:461–7.
3. Butler JE, et al., Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic. Immunol Res. 2014. 59:81-108.