scholarly journals Epstein-Barr Virus Encodes Three Bona Fide Ubiquitin-Specific Proteases

2008 ◽  
Vol 82 (21) ◽  
pp. 10477-10486 ◽  
Author(s):  
Ramakrishna Sompallae ◽  
Stefano Gastaldello ◽  
Sebastian Hildebrand ◽  
Nikolay Zinin ◽  
Gerco Hassink ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Markov Models ◽  
Sequence Similarity ◽  
Ubiquitin Proteasome System ◽  
Open Reading Frames ◽  
Deubiquitinating Enzymes ◽  
Sequence Alignments ◽  
Barr Virus ◽  
Epstein Barr ◽  
Pattern Searches

ABSTRACT Manipulation of the ubiquitin proteasome system (UPS) is emerging as a common theme in viral pathogenesis. Some viruses have been shown to encode functional homologs of UPS enzymes, suggesting that a systematic identification of these products may provide new insights into virus-host cell interactions. Ubiquitin-specific proteases, collectively known as deubiquitinating enzymes (DUBs), regulate the activity of the UPS by hydrolyzing ubiquitin peptide or isopeptide bonds. The prediction of viral DUBs based on sequence similarity with known enzymes is hampered by the diversity of viral genomes. In this study sequence alignments, pattern searches, and hidden Markov models were developed for the conserved C- and H-boxes of the known DUB families and used to search the open reading frames (ORFs) of Epstein-Barr virus (EBV), a large gammaherpesvirus that has been implicated in the pathogenesis of a broad spectrum of human malignancies of lymphoid and epithelial cell origin. The searches identified a limited number of EBV ORFs that contain putative DUB catalytic domains. DUB activity was confirmed by functional assays and mutation analysis for three high scoring candidates, supporting the usefulness of this bioinformatics approach in predicting distant homologues of cellular enzymes.

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

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.

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

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 3026-3032 ◽  
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.

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

Virology ◽  
2015 ◽  
Vol 483 ◽  
pp. 44-53 ◽  
Author(s):  
Takahiro Watanabe ◽  
Kenshiro Fuse ◽  
Takahiro Takano ◽  
Yohei Narita ◽  
Fumi Goshima ◽  
...  
Keyword(s):  
Viral Replication ◽  
Epstein Barr Virus ◽  
Open Reading Frames ◽  
Hek293 Cells ◽  
Barr Virus ◽  
Upstream Open Reading Frames ◽  
Epstein Barr ◽  
Reading Frames

scholarly journals Complete Nucleotide Sequence of the Rhesus Lymphocryptovirus: Genetic Validation for an Epstein-Barr Virus Animal Model

2002 ◽  
Vol 76 (1) ◽  
pp. 421-426 ◽  
Author(s):  
Pierre Rivailler ◽  
Hua Jiang ◽  
Young-gyu Cho ◽  
Carol Quink ◽  
Fred Wang
Keyword(s):  
Animal Model ◽  
Epstein Barr Virus ◽  
Interleukin 10 ◽  
Open Reading Frames ◽  
Gene Repertoire ◽  
Barr Virus ◽  
Viral Glycoproteins ◽  
Epstein Barr ◽  
Stimulating Factor ◽  
Reading Frames

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.

scholarly journals Structure and Coding Content of CST (BART) Family RNAs of Epstein-Barr Virus

2000 ◽  
Vol 74 (7) ◽  
pp. 3082-3092 ◽  
Author(s):  
Paul R. Smith ◽  
Orlando de Jesus ◽  
David Turner ◽  
Martine Hollyoake ◽  
Claudio Elgueta Karstegl ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Epstein Barr Virus ◽  
Growth Control ◽  
Genomic Analysis ◽  
Protein Product ◽  
Open Reading Frames ◽  
Barr Virus ◽  
Kinase C ◽  
Epstein Barr ◽  
Splicing Patterns

ABSTRACT CST (BART BARF0) family viral RNAs are expressed in several types of Epstein-Barr virus (EBV) infection, including EBV-associated cancers. Many different spliced forms of these RNAs have been described; here we have clarified the structures of some of the more abundant splicing patterns. We report the first cDNAs representing a full-length CST mRNA from a clone library and further characterize the transcription start. The relative abundance of splicing patterns and genomic analysis of the open reading frames (ORFs) suggest that, in addition to the much studied BARF0 ORF, there may be important products made from some of the upstream ORFs in the CST RNAs. Potential biological functions are identified for two of these. The product of the RPMS1 ORF is shown to be a nuclear protein that can bind to the CBF1 component of Notch signal transduction. RPMS1 can inhibit the transcription activation induced through CBF1 by NotchIC or EBNA-2. The protein product of another CST ORF, A73, is shown to be a cytoplasmic protein which can interact with the cell RACK1 protein. Since RACK1 modulates signaling from protein kinase C and Src tyrosine kinases, the results suggest a possible role for CST products in growth control, perhaps consistent with the abundant transcription of CST RNAs in cancers such as nasopharyngeal carcinoma.

scholarly journals Transcriptome Profiling of Epstein-Barr Virus Using Nanopore Sequencing

2020 ◽  
Author(s):  
Norbert Moldován ◽  
Kálmán Szenthe ◽  
Ferenc Bánáti ◽  
Ádám Fülöp ◽  
Zsolt Csabai ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Transcriptome Profiling ◽  
Open Reading Frames ◽  
Splice Isoforms ◽  
Rna Molecules ◽  
Barr Virus ◽  
Sequencing Technologies ◽  
Oxford Nanopore ◽  
Long Read ◽  
Epstein Barr

Abstract 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- and Pacific Biosciences RS II-based long-read sequencing technologies. In this work, we use the Oxford Nanopore Technologies MinION platform for the characterization of the EBV transcriptomic architecture. Both amplified and non-amplified cDNA sequencings were applied for the generation of transcription 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. This study detected novel short genes (embedded into longer host genes) containing 5’-truncated in-frame open reading frames (ORFs), which might 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 Ori-associated RNA molecules. Additionally, novel mono- and polycistronic, as well as complex transcripts have been uncovered. An intricate meshwork of transcriptional overlaps has also been revealed.

scholarly journals The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells

1992 ◽  
Vol 12 (1) ◽  
pp. 136-146
Author(s):  
S C Kenney ◽  
E Holley-Guthrie ◽  
E B Quinlivan ◽  
D Gutsch ◽  
Q Zhang ◽  
...  
Keyword(s):  
Gene Product ◽  
Epstein Barr Virus ◽  
Sequence Similarity ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Lymphoid Cells ◽  
Jurkat Cells ◽  
Barr Virus ◽  
Early Promoter ◽  
Epstein Barr

Regulation of replicative functions in the Epstein-Barr virus (EBV) genome is mediated through activation of a virally encoded transcription factor, Z (BZLF1). We have shown that the Z gene product, which binds to AP-1 sites as a homodimer and has sequence similarity to c-Fos, can efficiently activate the EBV early promoter, BMRF1, in certain cell types (i.e., HeLa cells) but not others (i.e., Jurkat cells). Here we demonstrate that the c-myb proto-oncogene product, which is itself a DNA-binding protein and transcriptional transactivator, can interact synergistically with Z in activating the BMRF1 promoter in Jurkat cells (a T-cell line) or Raji cells (an EBV-positive B-cell), whereas the c-myb gene product by itself has little effect. The simian virus 40 early promoter is also synergistically activated by the Z/c-myb combination. Synergistic transactivation of the BMRF1 promoter by the Z/c-myb combination appears to involve direct binding by the Z protein but not the c-myb protein. A 30-bp sequence in the BMRF1 promoter which contains a Z binding site (a consensus AP-1 site) is sufficient to transfer high-level lymphoid-specific responsiveness to the Z/c-myb combination to a heterologous promoter. That the c-myb oncogene product can interact synergistically with an EBV-encoded member of the leucine zipper protein family suggests c-myb is likely to engage in similar interactions with cellularly encoded transcription factors.

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

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 3026-3032 ◽  
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

Abstract 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.

Sign in / Sign up

Export Citation Format

Share Document