Epstein–Barr Virus MicroRNAs Are Evolutionarily Conserved and Differentially Expressed

PLoS Pathogens

Bryan R Cullen¹  Shihua Lu¹  Xuezhong Cai¹  Alexandra Schäfer¹  Nancy Raab-Traub²  Rachel Edwards²  John P Bilello³  Ronald C Desrosiers³ 

[1] Center for Virology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America;Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, United States of America

关键词: MicroRNAs;    Viral replication;    Viral gene expression;    Gene expression;    Viral evolution;    DNA sequence analysis;    Epstein-Barr virus;    Messenger RNA;   

DOI  :  10.1371/journal.ppat.0020023

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 ≥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.

【 授权许可】

CC BY