PRRS virus and cytokines (IFN-α and other):
IFN-α has key functions as an antiviral agent and modulator of the immune response. In the case of PRRS virus, it has been widely demonstrated that the virus inhibits the synthesis of IFN-α in macrophages and DCs.
It is thought that plasmacytoid dendritic cells (pDCs) are the major source of IFN-α; PRRS virus also prevents these cells to induce IFN-α production. As a matter of fact, the IFN-α responses of pDCs elicited by strong inducers as Transmissible gastroenteritis virus or TLR9 are completely abolished when exposed to PRRS virus.
Based on the above mentioned findings, it is not surprising that IFN-α cannot be detected or remains low in the serum and in the lungs of pigs in which the virus is actively replicating.
Several studies have demonstrated that the suppression of IFNs production is a major strategy of PRRS virus to modulate host antiviral defense. This suppression creates a favorable environment for the virus to replicate.
Non-structural proteins 1α, 1β, 2, 4, 5 and 11, and also N protein, are the PRRS virus proteins found to antagonize IFN-α and IFN-β induction. The suppression level on IFNs induction is strain dependent. Indeed, some PRRS virus strains seem able to downregulate proinflammatory cytokines such as IL-1β and TNF-α. Down-regulation of the TNF-α has been associated with nsp1a, nsp1b and nsp2.
PRRS virus may enhance production of IL-10, which has an important role in the regulation of the immune response: suppressing pro-inflammatory function of APC, limiting the production of pro-inflammatory cytokines -such as IL-1 and TNF-α, among others-, and inhibiting the cytokines released by Th1 and Th2 cells. It has been speculated that the early induction of IL-10 could be one of the factors favoring the extension of viremia length and infection.
It is important to highlight that available literature shows contradictory results about all the above mentioned cytokines. Probably, the variable effects that different isolates have could be invoked to explain these discrepancies.
Interestingly, some studies have described that some highly pathogenic strains are weak inducers of TNF-α; while other studies have showed that other highly pathogenic strains are strong inducers of TNF-α and inflammatory responses -responses that could be related to high fever and the injuries observed-.