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Updated: May 12, 2026

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed
Xuezhong Cai1, Alexandra Schäfer, Shihua Lu
1Center for Virology, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
Abstract:
The pathogenic lymphocryptovirus Epstein-Barr virus (EBV) is shown to express at least 17 distinct microRNAs (miRNAs) in latently infected cells. These are arranged in two clusters: 14 miRNAs are located in the introns of the viral BART gene while three are located adjacent to BHRF1. The BART miRNAs are expressed at high levels in latently infected epithelial cells and at lower, albeit detectable, levels in B cells. In contrast to the tissue-specific expression pattern of the BART miRNAs, the BHRF1 miRNAs are found at high levels in B cells undergoing stage III latency but are essentially undetectable in B cells or epithelial cells undergoing stage I or II latency. Induction of lytic EBV replication was found to enhance the expression of many, but not all, of these viral miRNAs. Rhesus lymphocryptovirus, which is separated from EBV by > or =13 million years of evolution, expresses at least 16 distinct miRNAs, seven of which are closely related to EBV miRNAs. Thus, lymphocryptovirus miRNAs are under positive selection and are likely to play important roles in the viral life cycle. Moreover, the differential regulation of EBV miRNA expression implies distinct roles during infection of different human tissues.
Insights
Epstein-Barr virus (EBV) expresses 17 microRNAs (miRNAs) in two clusters, BART and BHRF1, with distinct expression patterns in different cells. These viral miRNAs are conserved across lymphocryptoviruses and likely play key roles in infection.
Area of Science:
- Virology
- Molecular Biology
- Genomics
Background:
- Epstein-Barr virus (EBV) is a widespread human herpesvirus associated with various cancers.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression.
- EBV encodes multiple miRNAs, but their expression patterns and functions are not fully understood.
Purpose of the Study:
- To characterize the expression profiles of EBV-encoded miRNAs in different cellular contexts.
- To investigate the evolutionary conservation and potential roles of these miRNAs in the viral life cycle.
Main Methods:
- Quantitative PCR and Northern blotting to detect and quantify viral miRNA expression.
- Bioinformatic analysis to compare EBV miRNAs with those of related viruses.
- Analysis of miRNA expression during different stages of EBV latency and lytic replication.
Main Results:
- EBV expresses at least 17 miRNAs arranged in BART and BHRF1 clusters.
- BART miRNAs are highly expressed in latently infected epithelial cells, while BHRF1 miRNAs are abundant in stage III latently infected B cells.
- Viral miRNA expression is modulated during lytic replication, and homologous miRNAs are found in rhesus lymphocryptovirus, suggesting evolutionary conservation.
Conclusions:
- EBV miRNAs exhibit distinct tissue- and stage-specific expression patterns, implying specialized roles in different infection phases.
- The conservation of lymphocryptovirus miRNAs suggests their critical importance in viral pathogenesis.
- Understanding EBV miRNA regulation provides insights into viral persistence and oncogenesis.
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