Oncogenic Role of Epstein-Barr Virus-Encoded RNAs in Burkitt’s Lymphoma Cell Line Akata

Komano, Jun; Maruo, Seiji; Kurozumi, Koichi; Oda, Takanori; Takada, Kenzo

doi:10.1128/jvi.73.12.9827-9831.1999

Cited by 229 publications

(72 citation statements)

References 30 publications

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“…The ability of L22 to reverse the inhibition by EBER-1 of the dsRNA-mediated activation of PKR, has several implications. Recent reports have shown that high-level expression of EBER-1 can lead to the resistance of cells to physiological stresses and pro-apoptotic stimuli, can confer aspects of the transformed phenotype, and may result in outright tumorigenicity in some cases [9][10][11][12]. There is evidence to suggest that these effects are at least partially a consequence of the ability of the RNA to block the activation of PKR (which is strongly pro-apoptotic) [53][54][55][56][57][58].…”

Section: Discussionmentioning

confidence: 99%

Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein‐Barr virus small RNA EBER‐1

Elia

Vyas

Laing

et al. 2004

European Journal of Biochemistry

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Epstein-Barr virus (EBV) is a potent mitogenic and antiapoptotic agent for B lymphocytes and is associated with several different types of human tumour. The abundantly expressed small viral RNA, EBER-1, binds to the growth inhibitory and pro-apoptotic protein kinase R (PKR) and blocks activation of the latter by double-stranded RNA. Recent evidence has suggested that expression of EBER-1 alone in EBV-negative B cells promotes a tumorigenic phenotype and that this may be related to inhibition of the proapoptotic effects of PKR. The ribosomal protein L22 binds to EBER-1 in virus-infected cells, but the significance of this has not previously been established. We report here that L22 and PKR compete for a common binding site on EBER-1. As a result of this competition, L22 interferes with the ability of the small RNA to inhibit the activation of PKR by dsRNA. Transient expression of EBER-1 in murine embryonic fibroblasts stimulates reporter gene expression and partially reverses the inhibitory effect of PKR. However, EBER-1 is also stimulatory when transfected into PKR knockout cells, suggesting an additional, PKR-independent, mode of action of the small RNA. Expression of L22 prevents both the PKR-dependent and -independent effects of EBER-1 in vivo. These results suggest that the association of L22 with EBER-1 in EBV-infected cells can attenuate the biological effects of the viral RNA. Such effects include both the inhibition of PKR and additional mechanism(s) by which EBER-1 stimulates gene expression.

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Section: Discussionmentioning

confidence: 99%

Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein‐Barr virus small RNA EBER‐1

Elia

Vyas

Laing

et al. 2004

European Journal of Biochemistry

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“…3,26 The function of EBER RNAs is less clear; EBER expression is not required for B-cell transformation, 27 but recent studies suggest that EBER RNAs may play some role in oncogenesis. 28,29 Analysis of case 31 indicates that continued expression of EBER transcripts is not necessary for maintenance of the transformed phenotype in HRS cells. Although expression of EBER RNAs is generally considered a hallmark of latent EBV infection, lack of EBER expression has been described in EBV-associated hepatocellular carcinoma and EBV PCR-positive breast cancers.…”

Section: Case 31mentioning

confidence: 99%

Hodgkin lymphoma and Epstein‐Barr virus (EBV): No evidence to support hit‐and‐run mechanism in cases classified as non‐EBV‐associated

Gallagher

Perry

Freeland

et al. 2003

Intl Journal of Cancer

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The Epstein-Barr virus (EBV) is associated with a proportion of Hodgkin lymphoma (HL) cases, and this association is believed to be causal. The aetiology of cases lacking EBV in the tumour cells (EBV HRS-ve), which make up the majority of cases in western countries, is obscure. It has been suggested that EBV may also cause these tumours by using a hit-and-run mechanism. Support for this idea comes from the finding that most young adult patients, who are likely to have a good immune response to EBV, have EBV HRS-ve HL. We investigated this possibility using a combined serologic and molecular approach. Analysis of EBV seroprevalence rates in an epidemiologic study of young adult HL revealed that cases with EBV HRS-ve HL were more likely to be EBV-seronegative than controls. Furthermore, additional studies clearly showed that some HL patients have never been infected by EBV. Quantitative PCR was used to look for the presence of deleted EBV genomes in a series of adult cases with both EBV HRS؉ve and HRS-ve HL. Subgenomic fragments were detected in equimolar proportions. This study, therefore, found no evidence to support the idea that a hit-and-run mechanism involving EBV plays a role in the pathogenesis of HL. © 2003 Wiley-Liss, Inc. Key words: Hodgkin disease; human herpesvirus 4; hit-and-run; serology; quantitative PCRThe Epstein-Barr virus (EBV) is associated with a proportion of cases of Hodgkin lymphoma (HL), and this association is believed to be causal. 1,2 In EBV-associated cases, viral genomes are detected in Hodgkin and Reed-Sternberg (HRS) cells, the tumour cells in HL, and EBV latent gene products are expressed. 3 The latter include the EBER RNAs and EBNA1, LMP1 and LMP2 proteins; both LMP1 and 2 are postulated to play a role in disease pathogenesis. 3 EBER in situ hybridisation and LMP1 immunohistochemistry are generally used to determine the EBV status of HL tumours, and cases that are positive in these assays are referred to hereafter as EBV-associated or EBV HRSϩve. The aetiology of EBV HRS-ve cases remains obscure.The epidemiology of HL suggests that it is a heterogeneous condition, and the term HL most probably embraces more than one aetiologic entity. Consideration of differences in age-specific incidence patterns, along with risk factor data and the distribution of histologic subtypes, suggests that HL in children, young adults (15-34 years) and older adults (Ն50 years) have different aetiologies. 4 For the young adults, it has been further suggested that delayed exposure to a common childhood pathogen may play a role in disease pathogenesis. 5,6 In developed countries, EBV is associated with approximately one-third of cases, but in developing countries this proportion can be much higher. 1,7,8 Within individual geographical locales, there is also a suggestion that EBV HRSϩve HL is associated with lower socioeconomic status and greater material deprivation. 9,10 There are proportionately fewer EBV-associated cases in the young adult age group compared to the childhood and older adult age groups....

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“…Os EBER também se ligam à proteino-quinase ativada por RNA fita dupla (PKR), uma quinase que atua inativando o fator de iniciação de síntese protéica eIF-2, em função de estímulos antivirais de interferon (IFN) a e b. Tais efeitos variam desde inibição temporária da síntese protéica da célula hospedeira até apoptose. 47 A inserção dos genes EBER em linhagens de células Akata (de linfoma de Burkitt) EBV-negativas revelou que eles são responsáveis pela restituição da tumorigenicidade em camundongos SCID, crescimento em agar semi-sólido, resistência a estímulos apoptóticos e pelo aumento na expressão de BCL-2 48 . Tem sido demonstrado que os EBER podem induzir a expressão de interleucina-10 (IL-10) em linhagens de linfoma de Burkitt, sugerindo que os referidos transcritos virais possam promover uma supressão do sistema imune do hospedeiro mediada por IL-10 44 .…”

Section: Eber1 E Eber2unclassified

Papel dos genes latentes do vírus Epstein-Barr na oncogênese

Lima

Rabenhorst

2010

cmbio

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ResumoO Vírus Esptein-Barr (EBV) é amplamente distribuído no mundo, sendo estimado que mais de 90% da população adulta esteja infectada e que a maioria desses indivíduos transmita intermitentemente o vírus através da saliva. Além da associação com algumas doenças benignas, tais como mononucleose infecciosa, leucoplasia pilosa e doença linfoproliferativa pós-transplante, o EBV também tem sido associado a diversas neoplasias como linfoma de Burkitt, Doença de Hodgkin, carcinoma de nasofaringe, carcinoma gástrico, entre outros. Nas células tumorais, o referido vírus se apresenta no estado latente, podendo expressar alguns dos treze genes latentes, dependendo do tecido e do estado imunológico do hospedeiro. Apesar da vasta literatura acerca dos expressos latentes, os mecanismos envolvidos na oncogênese dos diversos tecidos ainda não estão totalmente esclarecidos. Nesse cenário, o presente artigo faz uma revisão acerca dos expressos latentes do EBV, abordando os padrões de latência observados nos cânceres associados, características estruturais e os efeitos descritos para cada expresso, com enfoque no papel oncogênico. Palavras-chave: vírus Epstein-Barr -genes latentes -oncogênese. AbstractEpstein-Barr virus (EBV) is widely distributed around the world, being estimated that more than 90% of the adult population is infected and that the majority transmits intermittently by the saliva. Besides the association with some benign diseases such as infectious mononucleosis, hairy leucoplakia, and post-transplant lymphoproliferative disorder, EBV has also been associated with several tumors such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, gastric carcinoma and others. In the tumor cells, the referred virus displays a latent status, in which it is able to express some of the thirteen latent genes depending of the tissue and host immunologic status. Despite the wide literature about the latent transcripts, the involved mechanisms are still not completely elucidated. In this scenario, this paper reviews the major data about EBV latent transcripts, pointing the latent patterns observed in the associated tumors, structural features and the reported effects for each transcript, with focus on the oncogenic role.

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Oncogenic Role of Epstein-Barr Virus-Encoded RNAs in Burkitt’s Lymphoma Cell Line Akata

Cited by 229 publications

References 30 publications

Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein‐Barr virus small RNA EBER‐1

Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein‐Barr virus small RNA EBER‐1

Hodgkin lymphoma and Epstein‐Barr virus (EBV): No evidence to support hit‐and‐run mechanism in cases classified as non‐EBV‐associated

Papel dos genes latentes do vírus Epstein-Barr na oncogênese

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