Transcriptome analysis reveals the molecular mechanism of hepatic fat metabolism disorder caused by Muscovy duck reovirus infection.

UNLABELLED

The aim of this work was to clarify the molecular mechanism underlying the fatty degeneration of livers infected with Muscovy duck reovirus (MDRV), which produces obvious white necrotic foci in the liver. Transcriptome data for MDRV-infected Muscovy duck livers and control livers were sequenced, assembled, and annotated with Illumina HiSeq 2000. The differentially expressed genes were screened and their functions were analysed. We also determined and confirmed the molecular mechanism of the hepatic fat metabolism disorder caused by MDRV infection. The expression of 4190 genes was higher in the infected livers than in the control livers, and the expression of 1113 genes was reduced. A Gene Ontology analysis showed that these genes were involved in 48 biological functions, and were significantly enriched in 237 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The free fatty acid content was significantly higher in the livers of infected Muscovy ducks than in the control livers (P < 0.01). The KEGG analysis showed that MDRV infection inhibited the cholesterol efflux from hepatic cells and reduced the expression of key enzymes involved in fatty acid degradation (scavenger receptor class b type 1, ABCG8, and APOA4), leading to the accumulation of fatty acids and cholesterol in the liver cells. In this study, we have identified the genes differentially expressed in livers infected by MDRV, from which we inferred the genes associated with lipodystrophia, and elucidated the molecular mechanism of the hepatic steatosis induced by MDRV.

ABBREVIATIONS

ABC: ATP binding cassette transport; ACADVL: acyl-CoA dehydrogenase, very long chain; ACAT: mitochondrial-like acetyl-CoA acetyltransferase A; ACAT2: acetyl-CoA acyltransferase 2; ACNAT2: acyl-coenzyme A amino acid N-acyltransferase 2-like; ACOT1: acyl-CoA thioesterase 1; ACOT7: acyl-CoA thioesterase 7; ACOX1: acyl-CoA oxidase 1, palmitoyl; ACSBG2: acyl-CoA synthetase bubblegum family member 2; ACSL1: acyl-CoA synthetase long-chain family member 1; ADH1: alcohol dehydrogenase 1; APOA4: apolipoprotein A-IV; ARV: avian reovirus; cDNA: complementary deoxyribonucleic acid; COG: Clusters of Orthologous Groups; DEG: differentially expressed gene; DGAT: diacylgycerol acyltransferase; DNA: deoxyribonucleic acid; ECI2: enoyl-CoA delta isomerase 2; EHHADH: enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase; FDR: false discovery rate; GCDH: Pseudopodoces humilis glutaryl-CoA dehydrogenase; GO: Gene Ontology; HADHA: hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit; I-FABP: intestinal fatty acid binding protein; KEGG: Kyoto Encyclopedia of Genes and Genomes; L-FABP: liver fatty acid binding protein; MDRV: Muscovy duck reovirus; MOI: multiplicity of infection; NPC1L1: Niemann-Pick C1-like 1; qPCR: real-time quantitative polymerase chain reaction; RNA: ribonucleic acid; RNase: ribonuclease; RNA-seq: RNA sequencing technology; RPKM: reads per kilobase per million mapped reads; SR-B1: scavenger receptor class b type 1.