As explained before, a first mechanism for escaping the immune response of the host will be the interaction with macrophages and dendritic cells, which are the bridges between the innate and the adaptive immune response.
PRRSV has several mechanisms for escaping the control of the immune system
These interactions may explain partially some of the unusual features of the adaptive immune response against PRRSV. Beyond this, several other mechanisms have been postulated for explaining the ability of the virus to escape the control of the immune system. For example, reported the existence of a decoy epitope close to the neutralization epitope known to exist in viral glycoprotein (GP 5).
The modification of such epitope results in an enhanced development of neutralizing antibodies. However, the role of the decoy epitope has been recently debated after evidencing that in vivo, only a minor proportion of circulating PRRSV virions retain such decoy epitope. Recently, in genotype 1 it has been shown that GP4 contains a hypervariable region where a neutralization epitope is located. This has been interpreted as a diverting mechanism of the virus.
Among the mechanisms that have been attributed to PRRSV for escaping the immune system, the presence of glycosylation sites in the envelope proteins has also been described. Several studies showed that the removal of glycosylation sites in the GP5 neutralization epitope results in enhanced immunogenicity and, contrarily, the addition of N-glycans decreases immunogenicity. However, the influence of this on the susceptibility to neutralization is not clear. A recent paper suggested that selection of PRRSV variants harbouring a highly glycosylated GP5 may be also related to other biological functionalities which are not connected with escaping from the immune system and thus the question of the relevance of glycosylations in GP5 remains unclear yet. Looking at GP3, another of the envelope proteins known to contain neutralization epitopes also showed that in genotype 2 PRRSV glycosylation of GP3 influences immune recognition.
Besides the above mentioned mechanisms, it is known that infected macrophages do not express PRRSV glycoproteins on the plasma membrane. This would prevent antibodies from binding to infected cells and killing them by complement and phagocytes. Additionally, it has been shown recently that cytotoxic T-lymphocytes are formed but have problems in eliminating PRRSV-infected macrophages. As a matter of fact, earlier observations showed that depletion of CD8+ cells did not result in exacerbation of the infection. Additionally, clear indications were found that apoptosis at the end of the replication cycle allows the virus to hide in apoptotic cell bodies.
Uptake of these bodies by macrophages then allows the virus to infect these cells.
One of the more controversial points about how PRRSV is able to escape the immune system, is whether or not infected pigs develop regulatory T cells (Treg). Several reports showed the induction of potential regulatory T cells with genotype 2 PRRSV but not with genotype 1. Whether those Treg are natural or inducible and whether they are detrimental or not is still a subject of debate.