In vitro Cytokine Responses to Virulent PRRS Virus Strains

Abstract

Porcine reproductive and respiratory syndrome (PRRS) affects farmed swine causing heavy direct and indirect losses. The infections sustained by PRRS viruses (PRRSV-1 and PRRSV-2) may give rise to severe clinical cases. This highlights the issue of PRRSV pathogenicity and relevant markers thereof. Since PRRSV strains can be discriminated in terms of immunotypes, we aimed to detect possible correlates of virulence in vitro based on the profile of innate immune responses induced by strains of diverse virulence. To this purpose, 10 field PRRSV isolates were investigated in assays of innate immune response to detect possible features associated with virulence. Tumor necrosis factor-α, interleukin (IL)-1beta, IL-8, IL-10, and caspase-1 were measured in cultures of PRRSV-treated peripheral blood mononuclear cells of PRRS-naive pigs, unable to support PRRSV replication. Two reference PRRSV strains (highly pathogenic and attenuated, respectively), were included in the screening. The PRRSV strains isolated from field cases were shown to vary widely in terms of inflammatory cytokine responses in vitro, which were substantially lacking with some strains including the reference, highly pathogenic one. In particular, neither the field PRRSV isolates nor the reference highly pathogenic strain gave rise to an IL-1beta response, which was consistently induced by the attenuated strain, only. This pattern of response was reversed in an inflammatory environment, in which the attenuated strain reduced the ongoing IL-1beta response. Results indicate that some pathogenic PRRSV strains can prevent a primary inflammatory response of PBMCs, associated with reduced permissiveness of mature macrophages for PRRSV replication in later phases.

Reappraisal of PRRS Control Strategies: The Way forward

“…Interestingly, this kind regulation is only observed in vitro under non-inflammatory conditions. Instead, in leukocytes previously exposed to inflammatory stimuli, virulent PRRSV strains enhance the inflammasome reaction and the IL-1beta response [28]. This is fully in line with in vivo findings of PRRSV infections leading to serious clinical outcomes: these are correlated with enhanced inflammatory cytokine responses, but not with the extent of viral replication [29].…”

“…Our studies in vitro [28] outlined the importance of the inflammasome response and IL-1beta production during PRRSV infection. In LPS-treated macrophages, PRRSV can enhance the inflammasome response by the small envelope protein E, giving rise to increased release of IL-1beta [106].…”

“…A primary inflammatory response leads to the development of virus-resistant pig macrophages [9]. Accordingly, this kind of response is sustained by attenuated PRRSV strains, whereas it is inhibited to a different extent by the virulent ones [28]. Interestingly, this kind regulation is only observed in vitro under non-inflammatory conditions.…”

“…In turn, IFN-alpha can induce high-titered release of IL-10 in LPS-stimulated monocytes and CD4+ T cells [54]. This is probably the mechanism underlying the IL-10 response in vitro of swine PBMC to some PRRSV strains [28,55].…”

“…the inhibition of the primary inflammatory response in macrophage precursors, in order to prevent the differentiation of PRRSV-resistant, mature pig macrophages [28] .…”