Resting B cells as a transfer vehicle for Epstein–Barr virus infection of epithelial cells

Shannon-Lowe, Claire; Nęuhierl, Bernhard; Baldwin, Gouri; Rickinson, Alan B.; Delecluse, Henri Jacques

doi:10.1073/pnas.0510512103

Cited by 176 publications

(171 citation statements)

References 31 publications

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…19 This sample, however, behaved very differently than all the samples reported here as infected cells could be grown in vitro for 18 passages. In contrast, EBV-infected primary cells from the present study stopped growing and underwent lytic replication.…”

Section: Discussionmentioning

confidence: 70%

“…19 Infections were performed with a recombinant EBV (293/ EBV-wt) that carries the GFP gene thereby allowing easy identification of infected cells. 20 Infected cultures were assayed for GFP expression and were found to contain 8.5 and 12% positive cells after transfer and direct infection, respectively (Fig.…”

Section: Ebv Produced In 293 Cells Infects Primary Epithelial Cellsmentioning

confidence: 99%

“…18 We have recently reported that B95.8 viruses produced in the 293 cell line and bound to primary resting B cells can infect epithelial cell lines with a 1000-fold higher efficiency than the same cell-free supernatant. 19 The increased efficiency of this transfer infection results from the formation of a synapse between B cells and epithelial cells that allow virus transfer. Here we show that the same source of virus has the ability to infect in vitro cultured primary epithelial cells with high efficiency.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Epstein‐Barr virus B95.8 produced in 293 cells shows marked tropism for differentiated primary epithelial cells and reveals interindividual variation in susceptibility to viral infection

Feederle

Nęuhierl

Bannert

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

Epstein-Barr virus (EBV), a well-characterised B-lymphotropic agent is aetiologically linked to B cell lymphoproliferations, but the spectrum of diseases the virus causes also includes oral hairy leukoplakia, a benign epithelial lesion, as well as carcinomas of the nasopharynx and of the stomach. However, it is still unclear how EBV accesses and transforms primary epithelial cells. Sixteen samples consisting of primary epithelial cells from the sphenoidal sinus or from tonsils were infected with GFP-tagged recombinant B95.8 EBVs produced in the 293 cell line. The rate of infection was assessed by counting GFP-positive cells and cells expressing viral proteins. Primary epithelial cells from all samples were found to be sensitive to EBV infection but there was a marked interindividual variation among the tested samples (2-48% positive cells). This suggests heterogeneity in terms of sensitivity to EBV infection in vivo and therefore possibly to EBV-associated diseases of the epithelium. The virus showed a preferential tropism for differentiated epithelial cells (p63 negative, involucrin positive). In all cases, infected cells expressed EBV lytic proteins but also the LMP1 protein. The viral tropism for differentiated cells and the permissivity of these cells for virus replication reproduced in vitro cardinal features of oral hairy leukoplakia. We have identified a source of EBV that shows unusually strong epitheliotropism for primary epithelial cells that will allow detailed analysis of virus-cell interactions during virus infection, replication and virus-mediated transformation. ' 2007 Wiley-Liss, Inc.

show abstract

Section: Discussionmentioning

confidence: 70%

Section: Ebv Produced In 293 Cells Infects Primary Epithelial Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Epstein‐Barr virus B95.8 produced in 293 cells shows marked tropism for differentiated primary epithelial cells and reveals interindividual variation in susceptibility to viral infection

Feederle

Nęuhierl

Bannert

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…EBV replicates in a permissive cell type in the oropharynx, probably specialised epithelial cells, that either binds virus directly or acquires virus by transfer from the surface of adjacent B cells (Figure 1) [12]. EBV infects epithelial cells through a CD21-independent mechanism, and the viral glycoprotein gH mediates EBV attachment to CD21-negative epithelial cells [13].…”

Section: Biology Of Ebv Infectionmentioning

confidence: 99%

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Kimura

Ito

Suzuki

et al. 2008

Reviews in Medical Virology

137

142

View full text Add to dashboard Cite

Because Epstein-Barr virus (EBV) is ubiquitous and persists latently in lymphocytes, simply detecting EBV is insufficient to diagnose EBV-associated diseases. Therefore, measuring the EBV load is necessary to diagnose EBVassociated diseases and to explore EBV pathogenesis. Due to the diverse biology of EBV, the significance of measuring EBV DNA and the optimal type of specimen differ among EBV-associated diseases. Recent advances in molecular technology have enabled the EBV genome to be quantitated rapidly and accurately. Real-time polymerase chain reaction (PCR) is a rapid and reliable method to quantify DNA and is widely used not only as a diagnostic tool, but also as a management tool for EBV-associated diseases. However, each laboratory currently measures EBV load with its own ''homebrew'' system, and there is no consensus on sample type, sample preparation protocol, or assay units. The EBV real-time PCR assay system must be standardised for large-scale studies and international comparisons.

show abstract

“…Following oral transmission, EBV replicates in the oropharyngeal epithelial cells and infects mucosal B cells, leading to a life-long persistence in the memory B-cell pool [1,2]. The primary infection occurs usually during childhood and is often asymptomatic; however, infection is manifested as acute infectious mononucleosis in a subset of patients [3].…”

Section: Introductionmentioning

confidence: 99%

Human peripheral blood and bone marrow Epstein–Barr virus‐specific T‐cell repertoire in latent infection reveals distinct memory T‐cell subsets

Guerreiro

Letsch

et al. 2010

Eur J Immunol

View full text Add to dashboard Cite

EBV infection leads to life-long viral persistence. Although EBV infection can result in chronic disease and malignant transformation, most carriers remain disease-free as a result of effective control by T cells. EBV-specific IFN-c-producing T cells could be demonstrated in acute and chronic infection as well as during latency. Recent studies, however, provide evidence that assessing IFN-c alone is insufficient to assess the quantity and quality of a T-cell response. Using overlapping peptide pools of latent EBV nuclear antigen 1 and lytic BZLF-1 protein and multicolor flow cytometry, we demonstrate that the majority of ex vivo EBV-reactive T cells in healthy virus carriers are indeed IL-2-and/or TNF-producing memory cells, the latter being significantly more frequent in BM. After in vitro expansion, a substantial number of EBV-specific CD4 1 and CD8 1 T cells retained a CC-chemokine receptor 7 (CCR7)-positive memory phenotype. Based on their cytokine profiles, six different EBV-specific T-cell subsets could be distinguished with TNF-single or TNF/IL-2-double producing cells expressing the highest CCR7 levels resembling earlydifferentiated memory T cells. Our study delineates the memory T-cell profile of a protective immune response and provides a basis for analyzing T-cell responses in EBVassociated diseases.Key words: BM . EBV . Immune monitoring . Multifunctional T cells . T-cell memory IntroductionEBV is a human gamma herpesvirus that is widespread in all human populations. Following oral transmission, EBV replicates in the oropharyngeal epithelial cells and infects mucosal B cells, leading to a life-long persistence in the memory B-cell pool [1,2]. The primary infection occurs usually during childhood and is often asymptomatic; however, infection is manifested as acute infectious mononucleosis in a subset of patients [3]. Despite the relatively benign course in most carriers, EBV reactivation is considered as a risk-factor both for malignant transformation and autoimmune diseases. The ability of the EBV encoded protein 1566LMP-1 to induce T-cell-independent immunoglobulin class switch DNA recombination and BAFF, a B-cell activating factor, that rescues self-reactive T cells, is considered to play an important role in the pathogenesis of EBV-related autoimmune and lymphoproliferative disease [4]. EBV is causatively linked to nasopharyngeal carcinoma and B-cell malignant diseases such as endemic Burkitt's lymphoma, Hodgkin's lymphoma and posttransplant lymphoproliferative diseases (PTLD) [5][6][7]. Recent data suggest that EBV is associated with various autoimmune diseases as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and primary Sjögren's syndrome [8,9]. Chronic active EBV infection can also cause Chronic Fatigue Syndrome, which is frequently associated with autoimmune thyreoiditis [10].The EBV cycle has two distinct stages, the latent infection where the genome is maintained at a constant copy number per cell and limited regions of the genome are expressed and the lytic cycle w...

show abstract

Resting B cells as a transfer vehicle for Epstein–Barr virus infection of epithelial cells

Abstract: Epstein-Barr virus (EBV),

Cited by 176 publications

References 31 publications

Epstein‐Barr virus B95.8 produced in 293 cells shows marked tropism for differentiated primary epithelial cells and reveals interindividual variation in susceptibility to viral infection

Epstein‐Barr virus B95.8 produced in 293 cells shows marked tropism for differentiated primary epithelial cells and reveals interindividual variation in susceptibility to viral infection

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Human peripheral blood and bone marrow Epstein–Barr virus‐specific T‐cell repertoire in latent infection reveals distinct memory T‐cell subsets

Contact Info

Product

Resources

About