Roles of Epstein-Barr virus BGLF3.5 gene and two upstream open reading frames in lytic viral replication in HEK293 cells

ABSTRACT We sequenced the rhesus lymphocryptovirus (LCV) genome in order to determine its genetic similarity to Epstein-Barr virus (EBV). The rhesus LCV encodes a repertoire identical to that of EBV, with 80 open reading frames, including cellular interleukin-10, bcl-2, and colony-stimulating factor 1 receptor homologues and an equivalent set of viral glycoproteins. The highly conserved rhesus LCV gene repertoire provides a unique animal model for the study of EBV pathogenesis.

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Both the rightward and the leftward open reading frames within the BamHI M DNA fragment of Epstein-Barr virus act as trans-activators of gene expression.

Journal of Virology ◽

10.1128/jvi.61.10.3310-3313.1987 ◽

1987 ◽

Vol 61 (10) ◽

pp. 3310-3313 ◽

Cited By ~ 11

Author(s):

M O Oguro ◽

N Shimizu ◽

Y Ono ◽

K Takada

Keyword(s):

Gene Expression ◽

Epstein Barr Virus ◽

Open Reading Frames ◽

Barr Virus ◽

Dna Fragment ◽

Epstein Barr ◽

Reading Frames

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Epstein-Barr virus genome packaging factors accumulate in BMRF1-cores within viral replication compartments

PLoS ONE ◽

10.1371/journal.pone.0222519 ◽

2019 ◽

Vol 14 (9) ◽

pp. e0222519 ◽

Cited By ~ 3

Author(s):

Atsuko Sugimoto ◽

Yoriko Yamashita ◽

Teru Kanda ◽

Takayuki Murata ◽

Tatsuya Tsurumi

Keyword(s):

Viral Replication ◽

Epstein Barr Virus ◽

Virus Genome ◽

Genome Packaging ◽

Barr Virus ◽

Epstein Barr

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Epstein-Barr Virus Immediate-Early Protein BRLF1 Induces the Lytic Form of Viral Replication through a Mechanism Involving Phosphatidylinositol-3 Kinase Activation

Journal of Virology ◽

10.1128/jvi.75.13.6135-6142.2001 ◽

2001 ◽

Vol 75 (13) ◽

pp. 6135-6142 ◽

Cited By ~ 69

Author(s):

Catherine Dayle Darr ◽

Amy Mauser ◽

Shannon Kenney

Keyword(s):

Viral Replication ◽

Transcriptional Activation ◽

Epstein Barr Virus ◽

Adenovirus Vector ◽

Pi3 Kinase ◽

Immediate Early ◽

Kinase Activation ◽

Barr Virus ◽

Epstein Barr ◽

Phosphatidylinositol 3

ABSTRACT Expression of the Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 induces the lytic form of viral replication in most EBV-positive cell lines. BRLF1 is a transcriptional activator that binds directly to a GC-rich motif present in some EBV lytic gene promoters. However, BRLF1 activates transcription of the other IE protein, BZLF1, through an indirect mechanism which we previously showed to require activation of the stress mitogen-activated protein kinases. Here we demonstrate that BRLF1 activates phosphatidylinositol-3 (PI3) kinase signaling in host cells. We show that the specific PI3 kinase inhibitor, LY294002, completely abrogates the ability of a BRLF1 adenovirus vector to induce the lytic form of EBV infection, while not affecting lytic infection induced by a BZLF1 adenovirus vector. Furthermore, we demonstrate that the requirement for PI3 kinase activation in BRLF1-induced transcriptional activation is promoter dependent. BRLF1 activation of the SM early promoter (which occurs through a direct binding mechanism) does not require PI3 kinase activation, whereas activation of the IE BZLF1 and early BMRF1 promoters requires PI3 kinase activation. Thus, there are clearly two separate mechanisms by which BRLF1 induces transcriptional activation.

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Functional Interaction between Epstein-Barr Virus Replication Protein Zta and Host DNA Damage Response Protein 53BP1

Journal of Virology ◽

10.1128/jvi.00512-09 ◽

2009 ◽

Vol 83 (21) ◽

pp. 11116-11122 ◽

Cited By ~ 27

Author(s):

Sarah G. Bailey ◽

Elizabeth Verrall ◽

Celine Schelcher ◽

Alex Rhie ◽

Aidan J. Doherty ◽

...

Keyword(s):

Dna Damage ◽

Viral Replication ◽

Epstein Barr Virus ◽

Signal Transduction Pathway ◽

Human Herpesvirus ◽

Lytic Cycle ◽

Barr Virus ◽

Proteomic Approach ◽

Viral Genes ◽

Epstein Barr

ABSTRACT Epstein-Barr virus (EBV; human herpesvirus 4) poses major clinical problems worldwide. Following primary infection, EBV enters a form of long-lived latency in B lymphocytes, expressing few viral genes, and it persists for the lifetime of the host with sporadic bursts of viral replication. The switch between latency and replication is governed by the action of a multifunctional viral protein Zta (also called BZLF1, ZEBRA, and Z). Using a global proteomic approach, we identified a host DNA damage repair protein that specifically interacts with Zta: 53BP1. 53BP1 is intimately connected with the ATM signal transduction pathway, which is activated during EBV replication. The interaction of 53BP1 with Zta requires the C-terminal ends of both proteins. A series of Zta mutants that show a wild-type ability to perform basic functions of Zta, such as dimer formation, interaction with DNA, and the transactivation of viral genes, were shown to have lost the ability to induce the viral lytic cycle. Each of these mutants also is compromised in the C-terminal region for interaction with 53BP1. In addition, the knockdown of 53BP1 expression reduced viral replication, suggesting that the association between Zta and 53BP1 is involved in the viral replication cycle.

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Integrative profiling of Epstein–Barr virus transcriptome using a multiplatform approach

Virology Journal ◽

10.1186/s12985-021-01734-6 ◽

2022 ◽

Vol 19 (1) ◽

Author(s):

Ádám Fülöp ◽

Gábor Torma ◽

Norbert Moldován ◽

Kálmán Szenthe ◽

Ferenc Bánáti ◽

...

Keyword(s):

Epstein Barr Virus ◽

Open Reading Frames ◽

Integrative Approach ◽

Splice Isoforms ◽

Sequencing Platform ◽

Barr Virus ◽

Pacific Biosciences ◽

Sequencing Technologies ◽

Long Read ◽

Epstein Barr

Abstract Background Epstein–Barr virus (EBV) is an important human pathogenic gammaherpesvirus with carcinogenic potential. The EBV transcriptome has previously been analyzed using both Illumina-based short read-sequencing and Pacific Biosciences RS II-based long-read sequencing technologies. Since the various sequencing methods have distinct strengths and limitations, the use of multiplatform approaches have proven to be valuable. The aim of this study is to provide a more complete picture on the transcriptomic architecture of EBV. Methods In this work, we apply the Oxford Nanopore Technologies MinION (long-read sequencing) platform for the generation of novel transcriptomic data, and integrate these with other’s data generated by another LRS approach, Pacific BioSciences RSII sequencing and Illumina CAGE-Seq and Poly(A)-Seq approaches. Both amplified and non-amplified cDNA sequencings were applied for the generation of sequencing reads, including both oligo-d(T) and random oligonucleotide-primed reverse transcription. EBV transcripts are identified and annotated using the LoRTIA software suite developed in our laboratory. Results This study detected novel genes embedded into longer host genes containing 5′-truncated in-frame open reading frames, which potentially encode N-terminally truncated proteins. We also detected a number of novel non-coding RNAs and transcript length isoforms encoded by the same genes but differing in their start and/or end sites. This study also reports the discovery of novel splice isoforms, many of which may represent altered coding potential, and of novel replication-origin-associated transcripts. Additionally, novel mono- and multigenic transcripts were identified. An intricate meshwork of transcriptional overlaps was revealed. Conclusions An integrative approach applying multi-technique sequencing technologies is suitable for reliable identification of complex transcriptomes because each techniques has different advantages and limitations, and the they can be used for the validation of the results obtained by a particular approach.

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An RS Motif within the Epstein-Barr Virus BLRF2 Tegument Protein Is Phosphorylated by SRPK2 and Is Important for Viral Replication

PLoS ONE ◽

10.1371/journal.pone.0053512 ◽

2013 ◽

Vol 8 (1) ◽

pp. e53512 ◽

Cited By ~ 9

Author(s):

Melissa Duarte ◽

Lili Wang ◽

Michael A. Calderwood ◽

Guillaume Adelmant ◽

Makoto Ohashi ◽

...

Keyword(s):

Viral Replication ◽

Epstein Barr Virus ◽

Tegument Protein ◽

Barr Virus ◽

Epstein Barr

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Expression of Epstein-Barr Virus BamHI-A Rightward Transcripts in Latently Infected B Cells From Peripheral Blood

Blood ◽

10.1182/blood.v93.9.3026.409k28_3026_3032 ◽

1999 ◽

Vol 93 (9) ◽

pp. 3026-3032 ◽

Cited By ~ 7

Author(s):

Honglin Chen ◽

Paul Smith ◽

Richard F. Ambinder ◽

S. Diane Hayward

Keyword(s):

B Cells ◽

Peripheral Blood ◽

Epstein Barr Virus ◽

Open Reading Frames ◽

Viral Gene ◽

Barr Virus ◽

Restricted Form ◽

Latently Infected ◽

Epstein Barr

In addition to the Epstein-Barr virus (EBV) EBNA and LMP latency genes, there is a family of alternatively spliced BamHI-A rightward transcripts (BARTs). These latency transcripts are highly expressed in the EBV-associated malignancies nasopharyngeal carcinoma and Burkitt’s lymphoma, and are expressed at lower levels in latently EBV-infected B-cell lines. The contribution of the BARTs to EBV biology or pathogenesis is unknown. Resting B cells have recently been recognized as a reservoir for EBV persistence in the peripheral blood. In these cells, EBV gene expression is tightly restricted and the only viral gene known to be consistently expressed is LMP2A. We used cell sorting and reverse-transcriptase polymerase chain reaction (RT-PCR) to examine whether BARTs are expressed in the restricted form of in vivo latency. Our results demonstrated that RNAs with splicing diagnostic for transcripts containing the BART RPMS1 and BARFO open-reading frames (ORFs) were expressed in CD19+ but not in CD23+ B cells isolated from peripheral blood of healthy individuals. The product of the proximal RPMS1 ORF has not previously been characterized. The RPMS1 ORF was shown to encode a 15-kD protein that localized to the nucleus of transfected cells. Expression of the BARTs in peripheral blood B cells suggests that the proteins encoded by these transcripts are likely to be important for maintenance of in vivo latency.

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