Signature of genome wide gene expression in classical swine fever virus infected macrophages and PBMCs of indigenous vis-a-vis crossbred pigs.

The genetic basis of differential host immune response vis-à-vis transcriptome profile was explored in PBMCs of indigenous (Ghurrah) and crossbred pigs after classical swine fever vaccination and in monocyte derived macrophages (MDMs) challenged with virulent classical swine fever (CSF) virus. The humoral immune response (E2 antibody) was higher (74.87%) in crossbred than indigenous pigs (58.20%) at 21st days post vaccination (21dpv). The rate of reduction of ratio of CD4+/CD8+ was higher in crossbred pigs than indigenous pigs at 7th days post vaccination (7dpv). The immune genes IFIT1, IFIT5, RELA, NFKB2, TNF and LAT2 were up regulated at 7dpv in RNA seq data set and was in concordance during qRT-PCR validation. The Laminin Subunit Beta 1 (LAMB1) was significantly (p ≤ 0.05) down-regulated in MDMs of indigenous pigs and consequently a significantly (p ≤ 0.01) higher copy number of virulent CSF virus was evidenced in macrophages of crossbred pigs than indigenous pigs. Activation of LXR:RXR pathway at 60 h post infection (60hpi) in MDMs of indigenous versus crossbred pigs inhibited nuclear translocation of NF-κB, resulted into transrepression of proinflammatory genes. But it helped in maintenance of HDL level by lowering down cholesterol/LDL level in MDMs of indigenous pigs. The key immune genes (TLR2, TLR4, IL10, IL8, CD86, CD54, CASP1) of TREM1 signaling pathway were upregulated at 7dpv in PBMCs but those genes were downregulated at 60hpi in MDMs indigenous pigs. Using qRT-PCR, the validation of differentially expressed, immunologically important genes (LAMB1, OAS1, TLR 4, TLR8 and CD86) in MDMs revealed that expression of these genes were in concordance with RNA-seq data.