Identification of miRNAs associated with dendritic cell dysfunction during acute and chronic hepatitis B virus infection

• Published in: Journal of medical virology 2021-06, Vol.93 (6), p.3697-3706
• Main Authors: Singh, Avishek Kumar, Rooge, Sheetalnath Babasaheb, Varshney, Aditi, Vasudevan, Madavan, Kumar, Manoj, Geffers, Robert, Kumar, Vijay, Sarin, Shiv Kumar
• Format: Article
• Language: English
• Subjects: acute viral hepatitis; Antigen presentation; Antigen processing; Antigens; chronic hepatitis B; Chronic infection; Cluster analysis; Clustering; Dendritic cells; Deregulation; DNA microarrays; Genes; HBe antigen; Hepatitis; Hepatitis B; Hepatitis B e antigen; Histocompatibility antigen HLA; Hsp90 protein; Immune clearance; Immune response; Immune system; Liver diseases; Major histocompatibility complex; microarray; MicroRNAs; miRNA; mRNA; Pathogenesis; Polymerase chain reaction; Ribonucleic acid; RNA; RT‐qPCR; Virology; Viruses
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.26629

The uptake or expression of hepatitis B virus (HBV) proteins by dendritic cells (DCs) is considered important for disease outcome. Differential expression of microRNA (miRNA) may have a role in viral persistence and hepatocellular injury. The miRNA expression was investigated by microarray in DCs from different stages of HBV infection and liver disease namely, immune active (IA; n = 20); low replicative (LR; n = 20); HBeAg negative (n = 20); acute viral hepatitis (AVH, n = 20) and healthy controls (n = 20). miRNA levels were analyzed by unsupervised hierarchical clustering and principal component analyses and validated by quantitative polymerase Chain Reaction (qPCR). The miRNA‐messenger RNA (mRNA)regulatory networks identified 19 miRNAs and 12 target gene interactions in major histocompatibility complex and other immune pathways. miR‐2278, miR‐615‐3p, and miR‐3681‐3p were downregulated in the IA group compared to healthy control, miR‐152‐3p and miR‐3613‐3p in the LR group compared to IA group and miR‐152‐3p and miR‐503‐3p in HBe negative compared to LR group. However, miR‐7‐1‐1‐3p, miR‐192‐5p, miR‐195‐5p, and miR‐32‐5p in LR, miR‐342‐3p, and miR‐940 in HBe negative, and miR‐34a‐5p, miR‐130b‐3p, miR‐221‐3p, miR‐320a, miR‐324‐5p, and miR‐484 in AVH were upregulated. Further, qPCR confirmed changes in miRNA levels and their target genes associated with antigen processing and presentation. Thus, a deregulated network of miRNAs‐mRNAs in DCs seems responsible for an impaired immune response during HBV pathogenesis. Highlights Distinct miRNA expression patterns were observed in DCs of healthy control, AVH and CHB patients. Specific clustering of HBeAg negative, Immune Active and low replicative groups was observed among CHB patients. The regulatory network identified 19 novel miRNAs and 12 target genes in DC‐related immune dysfunction in hepatitis B patients. Genes of MHC pathways such as HLA‐A, HLA‐B, HLA‐C, HSP‐70, HSP90, CANX and CALR could be critical for DCs dysfunction. Regulation of unique clusters of miRNAs and their target genes may be responsible for viral clearance or persistence.