The impact of CSFV on the immune response to control infection

Abstract

The severity of the acute form of CSF is responsible for the high mortality rate and has been the subject of many studies. Nevertheless, some animals are likely to develop a mild, chronic, or unapparent form of the disease. Paradoxically, this clinical form of the disease has not been well studied, especially regarding its pathogenesis. In this study, we investigated the infection in domestic pigs that is caused by the CSFV Cat01 strain, which is responsible for the 2001-2002 CSFV outbreak in Catalonia, Spain, and which caused mild and nonspecific clinical signs compared to the infection that is caused by another CSFV strain that is responsible for inducing severe clinical symptoms of disease. We assessed the impact of the CSFV infection in the immune system of domestic pigs, mainly on the kinetics of different cytokines, such as IFN-α (innate immunity) and IFN-γ (adaptive immune response), during the first weeks after infection. In addition, we evaluated the impact on the induction of the humoral response and its relation to the course of infection and the RNA CSFV viral load. The IFN-α levels in the serum samples from the pigs that developed a milder form of the CSF disease (infected with Cat01 strain) were lower than those that were detected in the pig with severe clinical CSF signs (Margarita strain). After infection with Cat01 strain, the IFN-γ levels in response to CSFV were detected in addition to the humoral response. Interestingly, in the serum samples of these animals, we detected the lowest load of CSFV RNA. Similarly, the lowest viral load levels were detected in the tonsils of these pigs. Both the T cells and the humoral response that were generated in most of the pigs that were infected with strain Cat01 may be related to the protection in the symptom progression of CSF against this viral strain. These results explain the antiviral role of IFN-γ in the absence of an antibody response. Likewise, these results corroborate the relevance and relationship that exists between the intensity of the T cell response and the protection against CSFV replication. Additionally, these results also explain how the failure to induce optimal levels of humoral and cellular responses after CSFV infection promotes the spread and persistence of the virus.

Treatment with interferon-alpha delays disease in swine infected with a highly virulent CSFV strain

“…Virulence studies using recombinant CSFV harboring modified forms of N pro , which should alter IFN induction/production rendered controversial results (Mayer et al, 2004;Ruggli et al, 2009;Tamura et al, 2014). Interestingly, a direct correlation between the virulence of a CSFV strain and the amount of IFN produced during the infection in swine has been reported (Renson et al, 2010;Summerfield et al, 1998;Tarradas et al, 2014), challenging the hypothesis that inhibition of host IFN is a critical step during infection, particularly with highly virulent CSFV strains. More recently, Tamura et al (2014) have shown that functional N pro influences the innate immune response at local sites of virus replication in pigs thus contributing to pathogenicity in synergy with viral replication.…”

Low CD4/CD8 ratio in classical swine fever postnatal persistent infection generated at 3 weeks after birth

“…The Catalonia 01 (Cat01) strain used in this study belongs to the CSFV 2.3 genogroup (Pérez et al., ). This strain has been characterized as a moderately virulent strain (Tarradas et al., ). Alfort 187 strain was used in the neutralisation peroxidase‐linked assay (NPLA).…”

Classical Swine Fever—An Updated Review

“…This is particularly important for clinical diagnosis. Infections with highly virulent CSFV strains such as “Margarita” or “Koslov” (the ones that are often used for vaccine testing) show a less age-dependent clinical course and may result in 100% mortality in all age classes of animals and severe neurological signs within 7 to 10 days (see, e.g., [112]).…”

“…There seems to be a correlation between high interferon (IFN)-α in the serum and disease severity and virulence of the strain involved [140,141]. High IFN-α concentrations are found as early as two days post infection, prior to the onset of clinical symptoms [112]. These findings are confirmed by microarray analyses of peripheral blood monocytic cells derived from CSFV-infected pigs [142].…”