EBV miRNA expression profiles in different infection stages: A prospective cohort study

Abstract

The Epstein-Barr virus (EBV) produces different microRNAs (miRNA) with distinct regulatory functions within the infectious cycle. These viral miRNAs regulate the expression of viral and host genes and have been discussed as potential diagnostic markers or even therapeutic targets, provided that the expression profile can be unambiguously correlated to a specific stage of infection or a specific EBV-induced disorder. In this context, miRNA profiling becomes more important since the roles of these miRNAs in the pathogenesis of infections and malignancies are not fully understood. Studies of EBV miRNA expression profiles are sparse and have mainly focused on associated malignancies. This study is the first to examine the miRNA profiles of EBV reactivation and to use a correction step with seronegative patients as a reference. Between 2012 and 2017, we examined the expression profiles of 11 selected EBV miRNAs in 129 whole blood samples from primary infection, reactivation, healthy carriers and EBV seronegative patients. Three of the miRNAs could not be detected in any sample. Other miRNAs showed significantly higher expression levels and prevalence during primary infection than in other stages; miR-BHRF1-1 was the most abundant. The expression profiles from reactivation differed slightly but not significantly from those of healthy carriers, but a specific marker miRNA for each stage could not be identified within the selected EBV miRNA targets.

Latency and lytic replication in Epstein–Barr virus-associated oncogenesis

“…These genes of the latent EBV infection encode 8 EBV proteins, 2 Epstein-Barr virus encoded small RNAs (EBERs) that are not translated and 25 pre-miRNAs that give rise to at least 44 miRNAs 20,25 . All of these can be found in LCLs, naïve tonsillar B cells of healthy virus carriers and nearly all tonsillar B cells of individuals with infectious mononucleosis 21,26,27 (Figure 1). The respective viral gene expression program is called latency III.…”

Epstein–Barr Virus: How Its Lytic Phase Contributes to Oncogenesis

“…The BART miRNAs are detected at all phases of EBV’s life cycle, while the BHRF1 miRNAs are not detected in some cells in culture and are when the same cells are induced to enter their lytic phase [ 83 ]. The levels of one of the BHRF1 miRNAs also correlates with viral load in the blood of patients consistent with it being expressed preferentially during EBV’s lytic phase [ 84 ]. The BHRF1 miRNAs are found immediately after infection of primary B cells and in some cases of post-transplant lymphoproliferative disease [ 85 , 86 ].…”

Epstein barr virus encodes miRNAs to assist host immune escape

“…The BHRF1-Cluster region transcribes three miRNA precursors (EBV-miR-BHRF1-1~3) to form four mature EBV-miR-BHRF1s. EBV miRNAs are named EBV-miR-BART1~22 and EBV-miR-BHRF1-1~3 according to the transcription region of their genome and the order in which they were found [31][32][33]. Interestingly, not all EBV strains have complete BART region.…”