Monocyte Transcriptome in Different Phases of Chronic Hepatitis B Virus Infection Uncovers Potential Functional Roles

The hepatitis B virus (HBV) chronic infection goes through different phases, i.e., immune tolerant (IT), immune clearance (IC), and inactive carrier (IN) resulting from the interplay of viral replication and immune response. Although the adaptive immune response is central to viral control, roles of the innate immune cells are less prominent. We explored monocyte transcriptome in these different phases of HBV infection to understand the nature of its involvement and identify unique differentially expressed genes (DEGs) in each phase. CD14+ peripheral blood monocytes were isolated from patients in the IT, IC, and IN phases and from healthy subjects and their RNA was sequenced. The significant DEGs were studied through gene annotation databases to understand differentially modulated pathways. The DEGs were further validated by qRT-PCR to identify genes that were uniquely expressed in each phase. It was found that TNFRSF12A was upregulated in all the HBV samples. The IN phase had six uniquely upregulated genes, i.e., PI3, EMP1, STX1A, RRAD, SPINK1, and SNORD3B-2. E2F7 was most consistently downregulated in the IT phase, and in the IC phase, IL23A and PI3 were specifically downregulated. Cut-off values were generated by ROC curve analysis to differentiate between the groups based on their expression levels. The monocyte functions are majorly suppressed in the IT and IC phases and are, however, somewhat metabolically active in the IN phase.