Systems Immunology Analyses Following Porcine Respiratory and Reproductive Syndrome Virus Infection and Vaccination

Bocard, Loïc Vivien; Kick, Andrew R.; Hug, Corinne; Lischer, Heidi E. L.; Käser, Tobias; Summerfield, Artur

doi:10.3389/fimmu.2021.779747

Cited by 11 publications

(12 citation statements)

References 27 publications

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“…Differential gene expression was enriched and ranked using GSEA. For ranking, the negative natural logarithm of the P-values with genes upregulated (positive log2-fold change values) and the natural logarithm of the P-values with genes downregulated were calculated [ 46 ]. Significant gene perturbations (FDRqvalue<0.05) were presented using BTM [ 20 ] adapted to the pig genome by replacing human genes with their pig homologs [ 47 ].…”

Section: Methodsmentioning

confidence: 99%

The baseline immunological and hygienic status of pigs impact disease severity of African swine fever

et al. 2022

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African Swine Fever virus (ASFV) is a large double-enveloped DNA virus of the Asfarviridae family that causes a lethal hemorrhagic disease in domestic pigs and wild boars. Since 2007, a highly virulent genotype II strain has emerged and spread in Europe and South-East Asia, where millions of animals succumbed to the disease. Field- and laboratory-attenuated strains of ASFV cause highly variable clinical disease severity and survival, and mechanisms remain unclear. We hypothesized that the immunological and hygienic status of pigs is a determinant of ASF disease course. Here we compared the immunological profile at baseline and in response to ASFV infection in specific pathogen-free (SPF) and farm-raised Large White domestic pigs. At steady state, SPF pigs showed lower white blood cell counts and a lower basal inflammatory and antiviral transcriptomic profile compared to farm pigs, associated with profound differences in gut microbiome composition. After inoculation with a highly virulent ASFV genotype II strain (Armenia 2008), severe clinical signs, viremia and pro-inflammatory cytokines appeared sooner in SPF pigs, indicating a reduced capacity to control early virus replication. In contrast, during infection with an attenuated field isolate (Estonia 2014), SPF pigs presented a milder and shorter clinical disease with full recovery, whereas farm pigs presented severe protracted disease with 50% lethality. Interestingly, farm pigs showed higher production of inflammatory cytokines, whereas SPF pigs produced more anti-inflammatory IL-1ra early after infection and presented a stronger expansion of leukocytes in the recovery phase. Altogether, our data indicate that the hygiene-dependent innate immune status has a double-edge sword impact on immune responses in ASF pathogenesis. While the higher baseline innate immune activity helps the host in reducing initial virus replication, it promotes immunopathological cytokine responses, and delays lymphocyte proliferation after infection with an attenuated strain. Such effects should be considered for live vaccine development and vigilance.

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Section: Methodsmentioning

confidence: 99%

The baseline immunological and hygienic status of pigs impact disease severity of African swine fever

et al. 2022

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“…As the induction of a humoral immune response has not been very successful in the control of these two diseases, an understanding of cellular immunity against these viruses has become a research hotspot in order to dissect the mechanism of immune protection and develop more effective vaccines. Numerous studies showed that PRRSV infection or attenuated modified live virus (MLV) vaccination induced a relatively weak and delayed cellular immune response, where increased cytotoxic CD8 T cells and CD4 + CD8 + T cells were detected at 4-5 weeks after infection or immunization [18,19], while IFN-γ-producing cells were occasionally detected as early as 2-3 weeks in individual animals after infection [20,21]. Although infection with the highly pathogenic PRRSV (HP PRRSV) strain was shown to cause the depletion/altered recruitment of Th cells, γδ T cells and B cells [22], IFN-γ-producing cells have been detected at 3 weeks post-infection [23].…”

Section: Introductionmentioning

confidence: 99%

Development of a Monoclonal Antibody to Pig CD69 Reveals Early Activation of T Cells in Pig after PRRSV and ASFV Infection

Tian

Hao

Dong

et al. 2022

Viruses

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The CD69 molecule, as an early activation marker of lymphocytes, is often used to assess the activation of cellular immunity. However, for pigs, an anti-pig CD69 antibody is not yet available for this purpose after infection or vaccination. In this study, a monoclonal antibody (mAb) against pig CD69 was produced by peptide immunization and hybridoma technique. One mAb (5F12) showed good reactivity with pig CD69 that was expressed in transfected-HEK-293T cells and on mitogen-activated porcine peripheral blood mononuclear cells (PBMCs) by indirect immunofluorescence assay and flow cytometry. This mAb did not cross-react with activated lymphocytes from mouse, bovine, and chicken. Epitope mapping showed that the epitope recognized by this mAb was located at amino acid residues 147–161 of pig CD69. By conjugating with fluorochrome, this mAb was used to detect the early activation of lymphocytes in PRRSV- and ASFV-infected pigs by flow cytometry. The results showed that PRRSV infection induced the dominant activation of CD4 T cells in mediastinal lymph nodes and CD8 T cells in the spleen at 14 days post-infection, in terms of CD69 expression. In an experiment on ASFV infection, we found that ASFV infection resulted in the early activation of NK cells, B cells, and distinct T cell subsets with variable magnitude in PBMCs, spleen, and submandibular lymph nodes. Our study revealed an early event of lymphocyte and T cell activation after PRRSV and ASFV infections and provides an important immunological tool for the in-depth analysis of cellular immune response in pigs after infection or vaccination.

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“…Differential gene expression was enriched and ranked using GSEA. For ranking, the negative natural logarithm of the P-values with genes upregulated (positive log2-fold change values) and the natural logarithm of the P-values with genes downregulated were calculated (Bocard et al, 2021). Significant gene perturbations (FDRqvalue<0.05) were presented using BTM (Li et al, 2014) adapted to the pig genome by replacing human genes with their pig homologs (Matthijs et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

The baseline immunological and hygienic status of pigs impact disease severity of African swine fever

Radulovic

Mehinagic

Wüthrich

et al. 2022

Preprint

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African Swine Fever virus (ASFV) is a large double-enveloped DNA virus of the Asfarviridae family that causes a lethal hemorrhagic disease in domestic pigs and wild boars. Since 2007, a highly virulent genotype II strain has emerged and spread in Europe and South-East Asia, where millions of animals succumbed to the disease. Field- and laboratory-attenuated strains of ASFV cause highly variable clinical disease severity and survival, and mechanisms remain unclear. We hypothesized that the immunological and hygienic status of pigs is a determinant of ASF disease course. Here we compared the immunological profile at baseline and in response to ASFV infection in specific pathogen-free (SPF) and farm-raised Large White domestic pigs. At steady state, SPF pigs showed lower white blood cell counts and a lower basal inflammatory and antiviral transcriptomic profile compared to farm pigs associated with profound differences in gut microbiome composition. After inoculation with a highly virulent ASFV genotype II strain (Armenia 2008), severe clinical signs, viremia and pro-inflammatory cytokines appeared sooner in SPF pigs, indicating a reduced capacity to control early virus replication. In contrast, during infection with an attenuated field isolate (Estonia 2014), SPF pigs presented a milder and shorter clinical disease with full recovery, whereas farm pigs presented severe protracted disease with 50% lethality. Interestingly, farm pigs showed higher production of inflammatory cytokines, whereas SPF pigs produced more anti-inflammatory IL-1ra early after infection, and presented a stronger expansion of leukocytes in the recovery phase. Altogether, our data indicate that the hygiene-dependent innate immune status has a double-edge sword impact on immune responses in ASF pathogenesis. While the higher baseline innate immune activity helps the host in reducing initial virus replication, it promotes immunopathological cytokine responses, and delays lymphocyte proliferation after infection with an attenuated strain. Such effects should be considered for live vaccine development and vigilance.

show abstract

Systems Immunology Analyses Following Porcine Respiratory and Reproductive Syndrome Virus Infection and Vaccination

Cited by 11 publications

References 27 publications

The baseline immunological and hygienic status of pigs impact disease severity of African swine fever

The baseline immunological and hygienic status of pigs impact disease severity of African swine fever

Development of a Monoclonal Antibody to Pig CD69 Reveals Early Activation of T Cells in Pig after PRRSV and ASFV Infection

The baseline immunological and hygienic status of pigs impact disease severity of African swine fever

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