The challenge of PRRS immunology

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is one of the most challenging subjects of research in veterinary viral immunology, and the immune response against PRRS virus (PRRSV) still is poorly understood. Infected pigs develop a strong and rapid humoral response but these initial antibodies do not confer protection and can even be harmful by mediating an antibody-dependent enhancement of disease. In contrast, development of neutralising antibodies (NAs) is delayed and generation of cell-mediated immune responses, such as PRRSV-specific interferon (IFN)-gamma secreting cells, is initially erratic. In spite of this, induction of strong and rapid NAs and IFN-gamma responses seem to be required for effective vaccination. PRRSV strongly modulates the host's immune responses. The virus inhibits key cytokines, such as IFN-alpha, and may induce regulatory cytokines, such as interleukin (IL)-10. Development of NAs seems to be impaired by the existence of a decoy epitope close to the main neutralisation epitope in glycoprotein 5. This ability to modulate the host immune response probably varies among strains or isolates. The genetic diversity of the virus is very high and it has been shown that this diversity can have serious implications for the development of vaccines, since the immunity induced by one strain may be only partial against a different strain, even within the same genotype. With this panorama, the development of newer and universally efficacious PRRSV vaccines is challenging, but the present state of knowledge allows optimism if collaborative efforts are undertaken in the scientific community.

The N-N non-covalent domain of the nucleocapsid protein of type 2 porcine reproductive and respiratory syndrome virus enhances induction of IL-10 expression

“…IL-10 was originally named 'cytokine synthesis inhibiting factor', since it can inhibit the transcription and translation of a variety of inflammatory cytokines (Donnelly et al, 2004). IL-10 is expressed by dendritic cells (DCs) IL-10 is thought to play an important role in the immunopathogenesis of PRRSV infection (Mateu & Diaz, 2008). PRRSV infection can upregulate IL-10 expression (Charerntantanakul et al, 2006;, which causes an imbalance between proinflammatory cytokines, such as TNF-a, and impairment of the immune response in the lungs (Gó mez-Laguna et al, 2013).…”

Immunological and biochemical characterisation of 7ap, a short protein translated from an alternative frame of ORF7 of PRRSV

“…Type I PRRSV, also known as the European genotype, is prevalent in Europe (although it may also cause infections in Asia and North America), while type II, also known as the North American genotype, causes infections mainly in China and North America (Stadejek et al, 2006;Shi et al, 2010). The high genetic diversity of PRRSV hinders the development of protective measures against the virus (Mateu and Diaz, 2008). Despite extensive scientific efforts and the substantial financial investments by stakeholders, currently there is no effective vaccine against the virus on the market (Zuckermann et al, 2007;Charerntantanakul, 2012;Tóth et al, 2016).…”

“…Presence of non-neutralising antibodies in the early stages of the infection could enhance viral replication in alveolar macrophages due to antibody-dependent enhancement. The virus can evade the immune response of the host using several other strategies including delaying and inhibiting interferon response of the host cells, interfering with antigen presentation, masking neutralising epitopes by glycan shielding, and using decoy epitopes to prevent fast and effective humoral immune response (Lopez and Osorio, 2004;Mateu and Diaz, 2008).…”

Porcine Herd Health Management Practices for the Control of PRRSV Infection

“…Such variability is largely attributed to genetical and antigenical heterogeneity between isolates mainly among European and American isolates, but also within the same area or the same farm. The high heterogeneity among PRRSV strains is likely to be the main obstacle to effective control of PRRSV infection using current commercial vaccines (MLV and inactivated), since the immunity induced by one strain may be only partial against a different strain, even within the same genotype (Mateu & Diaz, 2008;Kimman et al, 2009). However, vaccine efficacy may be associated with an efficient cell-mediated immunity and it is not only related with its immunological properties, but also with the characteristics of the challenging strain to trigger an immune response (Martelli et al, 2009).…”