Abstract:Epstein-Barr virus (EBV)BamHI-A rightward transcripts (BARTs; also designated complementary strand transcripts or CSTs) have been demonstrated to contain several splicing forms in EBV-infected cells. To date, however, little is known about the actual full-length splicing form and its functions. In the present study, we proved that six forms of BARTs were present in EBV-positive cell lines and various tissue specimens with different EBV infection patterns. Of the BART-encoded genes, mRNA of four major splicing … Show more
“…RNA was extracted from the samples with TRIzol ™ reagent (Gibco‐BRL, Gaithersburg, MD, U.S.A.), and the cDNA was amplified by PCR using EBER1‐specific and Bam HI A rightward transcripts (BARTs)‐specific primers, as described previously . The integrity of the RNA was checked by the parallel amplification of beta‐2‐microglobulin (β2‐MG).…”
Section: Methodsmentioning
confidence: 99%
“…Primer sets for reverse-transcriptase polymerase chain reaction RNA was extracted from the samples with TRIzol TM reagent (Gibco-BRL, Gaithersburg, MD, U.S.A.), and the cDNA was amplified by PCR using EBER1-specific and BamHI A rightward transcripts (BARTs)-specific primers, as described previously. 11,12 The integrity of the RNA was checked by the parallel amplification of beta-2-microglobulin (b2-MG). To detect EBV reactivation, BZLF1 was amplified by RT-PCR, using BZLF1-specific outer primers: sense, 5ʹ-CATGTTTCAACCGC TCCGACTGG-3ʹ, and antisense, 5ʹ-GCGCAGCCTGTCATTTTCA GATG-3ʹ.…”
Summary
Background
Epstein‐Barr virus (EBV)‐associated T/natural‐killer lymphoproliferative disorders form a group of diseases that includes classical and systemic hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). Patients with systemic HV (sHV) and HMB often have a poor prognosis, although little is known about the prognostic factors.
Objectives
To elucidate the prognostic factors of HV and HMB.
Methods
We studied clinicopathological manifestations, routine laboratory findings, anti‐EBV titres, EBV DNA load and EBV‐encoded gene expression, including expression of BZLF1, in 50 patients with classical HV (cHV), sHV, HMB only and HMB with HV (HMB + HV), and further analysed 30 patients who were available for follow‐up.
Results
The median age of disease onset was 5 years (range 1–74). A follow‐up study indicated that fatal outcomes were observed in three of eight patients with sHV, two of six patients with HMB only, and two of five patients with HMB + HV. The main causes of death were complications from haematopoietic stem‐cell transplantation and multiorgan failure. There were no fatalities among the 11 patients with cHV. Univariate analysis revealed two poor prognostic indicators: (i) onset age > 9 years and (ii) the expression of an EBV‐encoded immediate–early gene transcript, BZLF1 mRNA, in the skin lesions (P < 0·001 and P = 0·003, respectively).
Conclusions
No prognostic correlation was observed in EBV‐infected lymphocyte subsets, anti‐EBV antibody titres or EBV DNA load. Late onset and EBV reactivation are both related to more severe phenotypes of the disease, and thus may predict a poor prognosis.
“…RNA was extracted from the samples with TRIzol ™ reagent (Gibco‐BRL, Gaithersburg, MD, U.S.A.), and the cDNA was amplified by PCR using EBER1‐specific and Bam HI A rightward transcripts (BARTs)‐specific primers, as described previously . The integrity of the RNA was checked by the parallel amplification of beta‐2‐microglobulin (β2‐MG).…”
Section: Methodsmentioning
confidence: 99%
“…Primer sets for reverse-transcriptase polymerase chain reaction RNA was extracted from the samples with TRIzol TM reagent (Gibco-BRL, Gaithersburg, MD, U.S.A.), and the cDNA was amplified by PCR using EBER1-specific and BamHI A rightward transcripts (BARTs)-specific primers, as described previously. 11,12 The integrity of the RNA was checked by the parallel amplification of beta-2-microglobulin (b2-MG). To detect EBV reactivation, BZLF1 was amplified by RT-PCR, using BZLF1-specific outer primers: sense, 5ʹ-CATGTTTCAACCGC TCCGACTGG-3ʹ, and antisense, 5ʹ-GCGCAGCCTGTCATTTTCA GATG-3ʹ.…”
Summary
Background
Epstein‐Barr virus (EBV)‐associated T/natural‐killer lymphoproliferative disorders form a group of diseases that includes classical and systemic hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). Patients with systemic HV (sHV) and HMB often have a poor prognosis, although little is known about the prognostic factors.
Objectives
To elucidate the prognostic factors of HV and HMB.
Methods
We studied clinicopathological manifestations, routine laboratory findings, anti‐EBV titres, EBV DNA load and EBV‐encoded gene expression, including expression of BZLF1, in 50 patients with classical HV (cHV), sHV, HMB only and HMB with HV (HMB + HV), and further analysed 30 patients who were available for follow‐up.
Results
The median age of disease onset was 5 years (range 1–74). A follow‐up study indicated that fatal outcomes were observed in three of eight patients with sHV, two of six patients with HMB only, and two of five patients with HMB + HV. The main causes of death were complications from haematopoietic stem‐cell transplantation and multiorgan failure. There were no fatalities among the 11 patients with cHV. Univariate analysis revealed two poor prognostic indicators: (i) onset age > 9 years and (ii) the expression of an EBV‐encoded immediate–early gene transcript, BZLF1 mRNA, in the skin lesions (P < 0·001 and P = 0·003, respectively).
Conclusions
No prognostic correlation was observed in EBV‐infected lymphocyte subsets, anti‐EBV antibody titres or EBV DNA load. Late onset and EBV reactivation are both related to more severe phenotypes of the disease, and thus may predict a poor prognosis.
“…Eight of these EBV transcripts ( BARF0 , BALF3 , BALF4 , BALF5 , A73 , RPMS1 , LF2 and LF1 ) are encoded in the Bam H1A region of the viral genome where the expressed viral miRs are also encoded. 10 , 65 , 85 Although the medical literature suggests that latent membrane protein 1 is infrequently expressed in infected gastric adenocarcinoma by protein assays, TCGA RNAseq revealed that both EBV latent membrane protein encoding mRNAs ( LMP1 , LMP2A ) were consistently expressed, albeit at low level. Latent membrane protein 2 or other viral gene products may contribute to hypermethylated DNA that is characteristic of infected cancers.…”
A small set of gastric adenocarcinomas (9%) harbor Epstein–Barr virus (EBV) DNA within malignant cells, and the virus is not an innocent bystander but rather is intimately linked to pathogenesis and tumor maintenance. Evidence comes from unique genomic features of host DNA, mRNA, microRNA and CpG methylation profiles as revealed by recent comprehensive genomic analysis by The Cancer Genome Atlas Network. Their data show that gastric cancer is not one disease but rather comprises four major classes: EBV-positive, microsatellite instability (MSI), genomically stable and chromosome instability. The EBV-positive class has even more marked CpG methylation than does the MSI class, and viral cancers have a unique pattern of methylation linked to the downregulation of CDKN2A (p16) but not MLH1. EBV-positive cancers often have mutated PIK3CA and ARID1A and an amplified 9p24.1 locus linked to overexpression of JAK2, CD274 (PD-L1) and PDCD1LG2 (PD-L2). Multiple noncoding viral RNAs are highly expressed. Patients who fail standard therapy may qualify for enrollment in clinical trials targeting cancer-related human gene pathways or promoting destruction of infected cells through lytic induction of EBV genes. Genomic tests such as the GastroGenus Gastric Cancer Classifier are available to identify actionable variants in formalin-fixed cancer tissue of affected patients.
“…However, there is still a lack of supporting evidence for the expression of endogenous BART proteins in EBV-infected cells ( 44 , 79 ). It is also surprising to note that the expression levels of BART are known to vary depending on whether the infection is lytic or latent ( 45 ). These findings demand further detailed investigation to elucidate the potential roles of the BART proteins in the pathogenesis of EBV-induced NPC.…”
The role of Epstein–Barr virus (EBV) infection in the development and progression of tumor cells has been described in various cancers. Etiologically, EBV is a causative agent in certain variants of head and neck cancers such as nasopharyngeal cancer. Proteins expressed by the EVB genome are involved in invoking and perpetuating the oncogenic properties of the virus. However, these protein products were also identified as important targets for therapeutic research in the past decades, particularly within the context of immunotherapy. The adoptive transfer of EBV-targeted T-cells as well as the development of EBV vaccines has opened newer lines of research to conceptualize novel therapeutic approaches toward the disease. This review addresses the most important aspects of the association of EBV with head and neck cancers from an immunological perspective. It also aims to highlight the current and future prospects of enhanced EBV-targeted immunotherapies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.