scholarly journals Molecular Basis of Epstein–Barr Virus Latency Establishment and Lytic Reactivation

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2344
Author(s):  
Takayuki Murata ◽  
Atsuko Sugimoto ◽  
Tomoki Inagaki ◽  
Yusuke Yanagi ◽  
Takahiro Watanabe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Basis ◽  
Epstein Barr Virus ◽  
Expression Patterns ◽  
3D Structure ◽  
Early Gene ◽  
Late Gene Expression ◽  
Barr Virus ◽  
Virus Latency ◽  
Epstein Barr

Epstein–Barr virus (EBV) is a causative agent of infectious mononucleosis and several types of cancer. Like other herpesviruses, it establishes an asymptomatic, life-long latent infection, with occasional reactivation and shedding of progeny viruses. During latency, EBV expresses a small number of viral genes, and exists as an episome in the host–cell nucleus. Expression patterns of latency genes are dependent on the cell type, time after infection, and milieu of the cell (e.g., germinal center or peripheral blood). Upon lytic induction, expression of the viral immediate-early genes, BZLF1 and BRLF1, are induced, followed by early gene expression, viral DNA replication, late gene expression, and maturation and egress of progeny virions. Furthermore, EBV reactivation involves more than just progeny production. The EBV life cycle is regulated by signal transduction, transcription factors, promoter sequences, epigenetics, and the 3D structure of the genome. In this article, the molecular basis of EBV latency establishment and reactivation is summarized.

scholarly journals Multiple Roles of Epstein-Barr Virus SM Protein in Lytic Replication

2007 ◽  
Vol 81 (8) ◽  
pp. 4058-4069 ◽  
Author(s):  
Zhao Han ◽  
Elessa Marendy ◽  
Yong-Dong Wang ◽  
Jing Yuan ◽  
Jeffery T. Sample ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Epstein Barr Virus ◽  
Lytic Replication ◽  
Late Gene ◽  
Late Gene Expression ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Sm Protein

ABSTRACT The effect of Epstein-Barr virus (EBV) SM protein on EBV gene expression was examined using a recombinant EBV strain with the SM gene deleted and DNA microarrays representing all known EBV coding regions. Induction of lytic EBV replication in the absence of SM led to expression of approximately 40% of EBV genes, but a block in expression of over 50% of EBV genes. Contrary to previous findings, several early genes were SM dependent, and lytic EBV DNA replication did not occur in the absence of SM. Notably, two genes essential for lytic EBV DNA replication, BSLF1 and BALF5, encoding EBV DNA primase and polymerase, respectively, were SM dependent. Lytic DNA replication was partially rescued by ectopic expression of EBV primase and polymerase, but virion production was not. Rescue of DNA replication only enhanced expression of a subset of late genes, consistent with a direct requirement for SM for late gene expression in addition to its contribution to DNA replication. Therefore, while SM is essential for most late gene expression, the proximate block to virion production by the EBV SM deletion strain is an inability to replicate linear DNA. The block to DNA replication combined with the direct effect of SM on late gene expression leads to a global deficiency of late gene expression. SM also inhibited BHRF1 expression during productive replication in comparison to that of cells induced into lytic replication in the absence of SM. Thus, SM plays a role in multiple steps of lytic cycle EBV gene expression and that it is transcript-specific in both activation and repression functions.

scholarly journals Heterogeneous, restricted patterns of Epstein–Barr virus (EBV) latent gene expression in patients with chronic active EBV infection

2001 ◽  
Vol 82 (10) ◽  
pp. 2385-2392 ◽  
Author(s):  
Mikio Yoshioka ◽  
Nobuhisa Ishiguro ◽  
Hiroaki Ishiko ◽  
Xiaoming Ma ◽  
Hideaki Kikuta ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Real Time ◽  
Real Time Pcr ◽  
Epstein Barr Virus ◽  
Clinical Symptoms ◽  
The Other ◽  
Early Gene ◽  
Barr Virus ◽  
Epstein Barr

Epstein–Barr virus (EBV) has been shown to infect T lymphocytes and to be associated with a chronic active infection (CAEBV), which has been recognized as a mainly non-neoplastic T-cell lymphoproliferative disorder (T-cell LPD). The systemic distribution of EBV genomes was studied, by real-time PCR, in multiple tissues from six patients with CAEBV, including three patients with T-cell LPD, one patient with B-cell LPD and two patients with undetermined cell-type LPD. There were extremely high loads of EBV genomes in all tissues from the patients. This reflects an abundance of circulating and infiltrating EBV-infected cells and a wide variety of clinical symptoms in the affected tissues. We chose one sample from each patient that was shown by real-time PCR to contain a high load of EBV genomes and examined the expression of EBV latent genes by RT–PCR. EBER1 and EBNA1 transcripts were detected in all samples. Only one sample also expressed EBNA2, LMP1 and LMP2A transcripts in addition to EBER1 and EBNA1 transcripts. Two of the remaining five samples expressed LMP1 and LMP2A transcripts. One sample expressed LMP2A but not LMP1 and EBNA2 transcripts. Another sample expressed EBNA2 but not LMP1 and LMP2A transcripts. The other sample did not express transcripts of any of the other EBNAs or LMPs. None of the samples expressed the viral immediate-early gene BZLF1. These results showed that EBV latent gene expression in CAEBV is heterogeneous and that restricted forms of EBV latency might play a pathogenic role in the development of CAEBV.

scholarly journals An Epigenetic Journey: Epstein-Barr Virus Transcribes Chromatinized and Subsequently Unchromatinized Templates during Its Lytic Cycle

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Adityarup Chakravorty ◽  
Bill Sugden ◽  
Eric C. Johannsen
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Epstein Barr Virus ◽  
Dna Amplification ◽  
Lytic Cycle ◽  
Late Gene ◽  
Late Gene Expression ◽  
Viral Dna ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACTThe Epstein-Barr virus (EBV) lytic phase, like those of all herpesviruses, proceeds via an orderly cascade that integrates DNA replication and gene expression. EBV early genes are expressed independently of viral DNA amplification, and several early gene products facilitate DNA amplification. On the other hand, EBV late genes are defined by their dependence on viral DNA replication for expression. Recently, a set of orthologous genes found in beta- and gammaherpesviruses have been determined to encode a viral preinitiation complex (vPIC) that mediates late gene expression. The EBV vPIC requires an origin of lytic replication incis, implying that the vPIC mediates transcription from newly replicated DNA. In agreement with this implication, EBV late gene mRNAs localize to replication factories. Notably, these factories exclude canonical histones. In this review, we compare and contrast the mechanisms and epigenetics of EBV early and late gene expression. We summarize recent findings, propose a model explaining the dependence of EBV late gene expression on lytic DNA amplification, and suggest some directions for future study.

scholarly journals The Epstein-Barr Virus BDLF4 Gene Is Required for Efficient Expression of Viral Late Lytic Genes

2015 ◽  
Vol 89 (19) ◽  
pp. 10120-10124 ◽  
Author(s):  
Takahiro Watanabe ◽  
Yohei Narita ◽  
Masahiro Yoshida ◽  
Yoshitaka Sato ◽  
Fumi Goshima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epstein Barr Virus ◽  
Lytic Replication ◽  
Late Gene ◽  
Late Gene Expression ◽  
Lytic Gene ◽  
Barr Virus ◽  
Efficient Expression ◽  
Epstein Barr ◽  
Lytic Genes

Epstein-Barr virus (EBV) is a gammaherpesvirus, associated with infectious mononucleosis and various types of malignancy. We focused here on the BDLF4 gene of EBV and identified it as a lytic gene, expressed with early kinetics. Viral late gene expression of the BDLF4 knockout strain was severely restricted; this could be restored by an exogenous supply of BDLF4. These results indicate that BDLF4 is important for the EBV lytic replication cycle, especially in late gene expression.

scholarly journals Induction of distinct gene expression patterns in lymphoid and epithelial cells by the BARF-1 gene of Epstein-Barr virus

2007 ◽  
Vol 2 (Suppl 1) ◽  
pp. S9
Author(s):  
A Zur Hausen ◽  
T Wiech ◽  
E Nikolopoulos ◽  
S Lassmann ◽  
T Heidt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Epstein Barr Virus ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Barr Virus ◽  
Distinct Gene ◽  
Epstein Barr
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