Abstract

Porcine circovirus-associated disease (PCVAD) is one of the most serious infectious diseases in pigs worldwide. The primary causative agent of PCVAD is porcine circovirus type 2 (PCV2), which can cause lymphoid depletion and immunosuppression in pigs. Our previous study demonstrated that Laiwu (LW) pigs, a Chinese indigenous pig breed, have stronger resistance to PCV2 infection than Yorkshire × Landrace (YL) pigs. In this study, we found that the YL pigs showed more severe lymphocyte apoptosis and higher viral load in the spleen tissue than LW pigs. To illustrate the differential gene expression between healthy and infected spleens, transcriptome profiling of spleen tissues from PCV2-infected and control YL pigs was compared by RNA sequencing. A total of 90 differentially expressed genes (DEGs) was identified, including CD207, RSAD2, OAS1, OAS2, MX2, ADRB3, CXCL13, CCR1, and ADRA2C, which were significantly enriched in gene ontology (GO) terms related to the defense response to virus and cell–cell signaling, and another nine DEGs, KLF11, HGF, PTGES3, MAP3K11, XDH, CYCS, ACTC1, HSPH1, and RYR2, which were enriched in GO terms related to regulation of cell proliferation or apoptosis. Among these DEGs, the CXCL13 gene, which can suppress lymphocyte apoptosis during PCV2 infection, was significantly down-regulated in response to PCV2 infection in YL but not in LW pigs. By analysis of the regulatory elements in the promoter and 3′-untranslated region (3′-UTR) of porcine CXCL13, we found that the single nucleotide polymorphism (SNP) −1014 G (LW) > A (YL) and the Sus scrofa microRNA-296-5p (ssc-miR-296-5p) participated in regulating CXCL13 expression during the response to PCV2 infection.

Highlights

  • Porcine circovirus type 2 (PCV2) is a virus containing a single-stranded circular DNA genome of only approximately 1.7 kb in size [1]

  • The results indicated that LW pigs had less lymphocyte apoptosis and viral load than Yorkshire × Landrace (YL) pigs, which might be associated with the different expression pattern of the CXCL13 gene between LW and YL pigs after PCV2 infection

  • Different pathological manifestations in spleen tissues of PCV2‐infected YL and LW pigs In YL pigs, which are more susceptible to PCV2 infection, overt lymphocyte depletion was observed in HE-stained histopathological slides of spleens from PCV2-infected YL pigs compared with mock-infected ones (Figures 1C and D), while in LW pigs, the number of lymphocytes was only slightly decreased after PCV2 infection (Figures 1A and B)

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Summary

Introduction

Porcine circovirus type 2 (PCV2) is a virus containing a single-stranded circular DNA genome of only approximately 1.7 kb in size [1]. PCV2 strains can be separated into five genotypes, composed of three major genotypes, PCV2a, PCV2b, and PCV2d, and two lowprevalence genotypes, PCV2c and PCV2e [2]. Porcine circovirus-associated disease (PCVAD) or porcine circovirus disease (PCVD) caused by PCV2 typically affects weaning piglets of 5–12 weeks and is one of the most. The hallmark lesions of PCVAD/PCVD occur in lymphoid tissues [3]. PCV2-infected lymphoid tissues show atrophic or necrotizing lesions with deletion of lymphocytes, destruction of lymphoid follicles, and infiltration by large histiocytes and multinucleated giant cells [7]. The mechanism by which PCV2 causes lymphoid depletion has yet to be identified definitively. Lymphoid depletion can be a direct consequence of viral replication or an indirect consequence of infection, for example due to cell apoptosis.

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