Comparative transcriptome analysis reveals induction of apoptosis in chicken kidney cells associated with the virulence of nephropathogenic infectious bronchitis virus

Abstract

Avian infectious bronchitis virus (IBV) that causes respiratory and nephritic diseases in chicken is a major poultry pathogen leading to serious economic loss worldwide. The nephropathogenic IBV strains cause nephritis and kidney lesions intrinsically and the pathogenic mechanism is still unclear. In the present study, SPF chicks were infected with three nephropathogenic IBVs of different virulence and their gene expression profiles in chicken kidney were compared at transcriptome level. As a result, 1279 differentially expressed (DE) genes were found in very virulent SCDY2 inoculated group, 145 in virulent SCK2 group and 74 in non-virulent LDT3-A group when compared to mock infected group. Gene Ontology (GO) and KEGG pathway enrichment analysis on SCDY2 group displayed that the up-regulated DE genes were mainly involved in cell apoptosis, and the down-regulated genes were involved in metabolic processes and DNA replication. Protein-Protein Interaction (PPI) analysis showed that DE genes in SCDY2 group formed a network, and the core of the network was composed by cell apoptosis and immune response proteins. The clustering of gene expression profile among the three virus inoculated groups indicated that the majority of up-regulated DE genes on apoptosis in very virulent SCDY2 group were up-regulated more or less in virulent SCK2 group and those down-regulated on innate immune response in SCDY2 group were also down-regulated differently in SCK2 group. In addition, the number of apoptotic cells detected experimentally in kidney tissue were very different among the three virus inoculated groups and were positively accordant with the viral titer, kidney lesions and viral virulence of each group. Taken all together, the present study revealed that virulent nephropathogenic IBV infection modified a number of gene expression and induction of apoptosis in kidney cells may be a major pathogenic determinant for virulent nephropathogenic IBV.

miR-146a-5p promotes replication of infectious bronchitis virus by targeting IRAK2 and TNFRSF18

“…The IBV strain Beaudette was kindly provided by Prof. Ding-xiang Liu, Nanyang Technological University. The LDT3-A, SCK2 and SCDY2 were nephropathogenic IBV strains and stored by the Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province [6]. The Vero and HEK 293T cell line was procured from the American type culture collection (ATCC CCL81).…”

“…Potential target mRNAs for miRNA-146a that expressed differently in the sequencing results were analyzed by miRanda. The mRNA and miRNA libraries used in this study were identified in our previous study [6,16]. mRNA expression of predicted genes in HD11 cells after transfection, mock-infected or transfection-infected lung tissues were assayed at 0, 12, 24 and 48 h of post infection.…”

“…Currently only IBV Beaudette strain can replicate in HD11 [4] or Vero [5] cell lines. Several recent works have proved the induction of apoptosis and suppression of immune response are related to the pathogenicity of nephropathogenic IBVs [6,7]. However, the key factor for these process during infection are still unclear.…”

“…In our previous study, we have described the transcriptome of chicken kidneys infected with nephropathogenic IBVs at mRNA and miRNA level. Chicken kidney infected with three nephropathogenic IBV with different virulence revealed the differentially expressed genes and miRNAs [6,16]. Among them, most of the differentially expressed (DE) mRNAs are related to immune response, cell apoptosis, DNA replication and metabolic pathways [6].…”

“…Chicken kidney infected with three nephropathogenic IBV with different virulence revealed the differentially expressed genes and miRNAs [6,16]. Among them, most of the differentially expressed (DE) mRNAs are related to immune response, cell apoptosis, DNA replication and metabolic pathways [6]. 58 differentially expressed miRNAs are considered responsible for the differentially expressed (DE) mRNAs.…”