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Low prevalence of antibody to human herpesvirus-6 (HHV-6) in Kadazans

Yadav M, Umamaheswari S, Ablashi DV

Southeast Asian J Trop Med Public Health, 1990 Jun;21(2):259-63.
PMID: 2173152

The prevalence of antibody to human herpesvirus type 6 (HHV-6) and Epstein-Barr virus (EBV) viral capsid antigens (VCA) were analysed in sera from Kadazans of Sabah, North Borneo. At a serum dilution of 10, about 34% were positive for HHV-6 antibody but in contrast all 95 individuals studied were positive for EBV VCA antibody. The study shows that HHV-6 and EBV infection occur independently. The low frequency of seropositive individuals in this community suggests that other than socioeconomic factors are responsible for the spread of the virus.

Matched MeSH terms: Herpesvirus 4, Human*
Epstein-Barr virus latent membrane protein-1 oncogene deletions: correlations with malignancy in Epstein-Barr virus--associated lymphoproliferative disorders and malignant lymphomas

Kingma DW, Weiss WB, Jaffe ES, Kumar S, Frekko K, Raffeld M

Blood, 1996 Jul 01;88(1):242-51.
PMID: 8704180

LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cell lines, nasopharyngeal carcinoma (NPC), a subset of Hodgkin's disease (HD), and in EBV-associated lymphoproliferative disorders (EBV-LPDs). Recently, focused deletions near the 3' end of the LMP-1 gene (del-LMP-1, amino acids 346-355), in a region functionally related to the half-life to the LMP-1 protein, have been reported frequently in human immunodeficiency virus (HIV)-associated HD (100%) and EBV+ Malaysian and Danish peripheral T-cell lymphomas (100%, 61% respectively), but less frequently in cases of HD not associated with HIV (28%, 33%) and infectious mononucleosis (33%). To further investigate the potential relationship of del-LMP-1 to EBV-LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases). The presence of EBV within lymphoid cells was confirmed by EBV EBER1 RNA in situ hybridization or by polymerase chain reaction (PCR) analysis. EBV strain type and LMP-1 deletion status were determined by PCR. EBV strain types segregated into two distinct distributions: HIV+ (9 A; 11 B) and non-HIV (19 A, 0 B), consistent with previous reports. Overall, del-LMP-1 were found in 1 of 5 (20%) Burkitt lymphomas (BL); 17 of 24 (71%) aggressive non-Hodgkin's lymphoma (agg-NHL), and 2 of 10 (20%) reactive lymphoid proliferations. Of the agg-NHLs, del-LMP-1 were present in 4 of 4 PT-ML (100%); 10 of 15 HIV+ ML (67%); and 3 of 5 nonimmunodeficiency malignant lymphoma (ML, 60%). A total of 2 of 7 (28%) sporadic EBV-associated lymphoid hyperplasias contained a del-LMP-1. All del-LMP-1 were identical by DNA sequence analysis. No correlation was identified between the presence of del-LMP-1 and the EBV strain type observed. The high incidence of del-LMP-1 observed in agg-NHLs (71%), in contrast to the relatively low incidence observed in reactive lymphoid proliferations (28%), suggests that the deleted form may be preferentially selected in lymphomatous processes. All posttransplant agg-NHLs contained a del-LMP-1, and a similar frequency of del-LMP-1 was observed in both HIV-associated ML (66%) and nonimmunodeficiency ML (60%), suggesting that impairment of immune function alone is not a requirement for the expansion of malignant cells infected by EBV stains containing the deleted LMP-1 gene.

Matched MeSH terms: Herpesvirus 4, Human/classification; Herpesvirus 4, Human/genetics; Herpesvirus 4, Human/pathogenicity*; Herpesvirus 4, Human/physiology
Fulltext Inhibitory activities of microalgal extracts against Epstein-Barr virus DNA release from lymphoblastoid cells

Kok YY, Chu WL, Phang SM, Mohamed SM, Naidu R, Lai PJ, et al.

J Zhejiang Univ Sci B, 2011 May;12(5):335-45.
PMID: 21528487 DOI: 10.1631/jzus.B1000336

This study aimed to assess the inhibitory activities of methanol extracts from the microalgae Ankistrodesmus convolutus, Synechococcus elongatus, and Spirulina platensis against Epstein-Barr virus (EBV) in three Burkitt's lymphoma (BL) cell lines, namely Akata, B95-8, and P3HR-1. The antiviral activity was assessed by quantifying the cell-free EBV DNA using real-time polymerase chain reaction (PCR) technique. The methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity and potent effect in reducing cell-free EBV DNA (EC(50)<0.01 µg/ml) with a high therapeutic index (>28000). After fractionation by column chromatography, the fraction from Synechococcus elongatus (SEF1) reduced the cell-free EBV DNA most effectively (EC(50)=2.9 µg/ml, therapeutic index>69). Upon further fractionation by high performance liquid chromatography (HPLC), the sub-fraction SEF1'a was most active in reducing the cell-free EBV DNA (EC(50)=1.38 µg/ml, therapeutic index>14.5). This study suggests that microalgae could be a potential source of antiviral compounds that can be used against EBV.

Matched MeSH terms: Herpesvirus 4, Human/drug effects*; Herpesvirus 4, Human/genetics
Fulltext The distinctive profile of risk factors of nasopharyngeal carcinoma in comparison with other head and neck cancer types

Abdulamir AS, Hafidh RR, Abdulmuhaimen N, Abubakar F, Abbas KA

BMC Public Health, 2008;8:400.
PMID: 19055849 DOI: 10.1186/1471-2458-8-400

Nasopharyngeal carcinoma (NPC) and other head and neck cancer (HNCA) types show a great epidemiological variation in different regions of the world. NPC has multifactorial etiology and many interacting risk factors are involved in NPC development mainly Epstein Barr virus (EBV). There is a need to scrutinize the complicated network of risk factors affecting NPC and how far they are different from that of other HNCA types.

Matched MeSH terms: Herpesvirus 4, Human/immunology; Herpesvirus 4, Human/isolation & purification
Quantification of Epstein-Barr virus DNA load, interleukin-6, interleukin-10, transforming growth factor-beta1 and stem cell factor in plasma of patients with nasopharyngeal carcinoma

Tan EL, Selvaratnam G, Kananathan R, Sam CK

BMC Cancer, 2006;6:227.
PMID: 16995954

Nasopharyngeal carcinoma (NPC) is a common epithelial neoplasm among the Chinese populations in Southern China and South East Asia. Epstein-Barr virus (EBV) is known to be an important etiologic agent of NPC and the viral gene products are frequently detected in NPC tissues along with elevated antibody titres to the viral proteins (VCA and EA) in a majority of patients. Elevated plasma EBV DNA load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the levels of certain interleukins and growth factors have also been implicated in NPC. The objectives of the present study are, 1) to investigate the correlations between plasma EBV DNA load and the levels of interleukin (IL)-6, IL-10, TGF-beta1 and SCF (steel factor) and 2) to relate these parameters to the stages of NPC and the effect of treatment.

Matched MeSH terms: Herpesvirus 4, Human/genetics; Herpesvirus 4, Human/isolation & purification*
Expression of retinoblastoma protein and P16 proteins in classic Hodgkin lymphoma: relationship with expression of p53 and presence of Epstein-Barr virus in the regulation of cell growth and death

Kim LH, Peh SC, Poppema S

Hum Pathol, 2006 Jan;37(1):92-100.
PMID: 16360421

Deregulation of several genes involved in cell cycle control has been reported in classic Hodgkin lymphoma (cHL). This study aimed to investigate the expression of tumor suppressor proteins (P16(INK4A), retinoblastoma protein, and p53) in cHL in relation to the proliferation and apoptosis of Hodgkin/Reed-Sternberg (H/RS) cells, correlating with the status of Epstein-Barr virus (EBV). A total of 66 cHL cases and 10 nonneoplastic reactive lymphoid tissues were retrieved from the archives. Immunohistochemistry technique was used for the detection of protein expression. Presence of EBV infection was detected by EBV early RNA in situ hybridization. p16(INK4A) gene deletion status was assessed by fluorescence in situ hybridization technique. Expression of P16(INK4A) was observed in 49.2% of the cases, whereas positive retinoblastoma protein and p53 expressions in the H/RS cells were detected in 89.1% and 81.5% of the cases, respectively. Epstein-Barr virus positivity was detected in 53.0% of the cases. Proliferation marker, Ki-67 expression, was observed in 86.7% of the cases. There was no significant correlation between the expression of the various tumor suppressor proteins and Ki-67. Retinoblastoma protein and p53 were also not associated with the presence of EBV. An inverse relationship was observed between the expression of P16(INK4A) and the presence of EBV. There were no significant homozygous or hemizygous deletions of the p16(INK4A) gene. However, an aberrant copy number of chromosome 9 with the loss of one or more p16(INK4A) loci was detected in all cases assessable by fluorescence in situ hybridization. Loss of function of one or more tumor suppressor proteins may be involved in defective cell regulation of H/RS cells. Epstein-Barr virus may have a role in inhibiting P16(INK4A) expression, thus resulting in a perturbed p16(INK4A)-Rb cell cycle checkpoint.

Matched MeSH terms: Herpesvirus 4, Human/genetics; Herpesvirus 4, Human/isolation & purification*
Spectrum of malignant lymphomas in Klang Hospital, a public hospital in Malaysia

Peh SC, Kim LH, Thanaletchimy N, Chai SP, Poppema S

Malays J Pathol, 2000 Jun;22(1):13-20.
PMID: 16329532

Lymphoma is a relatively common group of neoplasms diagnosed in hospital practice. This study aims to elucidate the pattern of this disease encountered in a public service hospital of the Ministry of Health, Malaysia.

Matched MeSH terms: Herpesvirus 4, Human/genetics; Herpesvirus 4, Human/isolation & purification
Dual variant of Epstein-Barr virus in Hodgkin/Reed-Sternberg cells: single-cell PCR study on latent membrane protein-1 gene

Kim LH, Peh SC, Poppema S

Int J Cancer, 2003 Nov 1;107(2):250-5.
PMID: 12949802

Isolation of single cells permits analysis of DNA or RNA from individual cells among heterogeneous populations. This technique is particularly useful in the study of classical Hodgkin's lymphoma (cHL) due to the scarcity of H/RS tumor cells among large numbers of reactive leukocytes. In a previous study, we found a high frequency of dual LMP-1 variant (concurrent presence of deleted and nondeleted variants) in cHL from whole-tissue sections. For the present study, we applied a single-cell isolation technique to determine the LMP-1 oncogene variant in EBV-associated H/RS cells. Five cases of EBV-infected cHL, containing nondeleted (n=1), deleted (n=1) and dual infection (n=3) based on whole-tissue section analysis, were selected for study. Paraffin-embedded tissue sections were stained with antibody to LMP-1 and positively stained H/RS cells isolated using a semiautomated micromanipulator. Each isolated single cell was subjected to PCR for amplification of the LMP-1 gene flanking the 30 bp deletion region and Xho1 restriction site. Cases with either nondeleted variant or the deleted variant showed similar LMP-1 variant expression in isolated single H/RS cells. However, 1 of the 3 cases with dual variants showed only the deleted variant in H/RS cells. The other 2 cases showed mixed patterns of deleted, nondeleted and dual LMP-1 variants in isolated single H/RS cells. All cases showed loss of the Xho1 restriction site, with the exception of the case with nondeleted LMP-1. Results of single-H/RS cell analysis of the Xho1 restriction site concur with those of whole-tissue section amplification. A mixed pattern of LMP-1 variants was observed in isolated H/RS cells, and it is speculated that this is due to the accumulation of mutation and deletion events.

Matched MeSH terms: Herpesvirus 4, Human/genetics; Herpesvirus 4, Human/isolation & purification*
Fulltext Regulation of S1PR2 by the EBV oncogene LMP1 in aggressive ABC-subtype diffuse large B-cell lymphoma

Vockerodt M, Vrzalikova K, Ibrahim M, Nagy E, Margielewska S, Hollows R, et al.

J Pathol, 2019 06;248(2):142-154.
PMID: 30666658 DOI: 10.1002/path.5237

The Epstein-Barr virus (EBV) is found almost exclusively in the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focused on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCLs and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL. These included the down-regulation of S1PR2, a sphingosine-1-phosphate (S1P) receptor that is transcriptionally down-regulated in ABC-DLBCL, and when genetically ablated leads to DLBCL in mice. Consistent with this, we found that LMP1-expressing primary ABC-DLBCLs were significantly more likely to lack S1PR2 expression than were LMP1-negative tumours. Furthermore, we showed that the down-regulation of S1PR2 by LMP1 drives a signalling loop leading to constitutive activation of the phosphatidylinositol-3-kinase (PI3-K) pathway. Finally, core LMP1-PI3-K targets were enriched for lymphoma-related transcription factors and genes associated with shorter overall survival in patients with ABC-DLBCL. Our data identify a novel function for LMP1 in aggressive DLBCL. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Matched MeSH terms: Herpesvirus 4, Human/genetics; Herpesvirus 4, Human/metabolism*
Identification of potential hot spots in the carboxy-terminal part of the Epstein-Barr virus (EBV) BNLF-1 gene in both malignant and benign EBV-associated diseases: high frequency of a 30-bp deletion in Malaysian and Danish peripheral T-cell lymphomas

Sandvej K, Peh SC, Andresen BS, Pallesen G

Blood, 1994 Dec 15;84(12):4053-60.
PMID: 7994023

In this study, we have sequenced the C-terminal part of the Epstein-Barr virus (EBV)-BNLF-1 gene encoding for the latent membrane protein-1 from tissues of EBV-positive Danish Hodgkin's disease (HD) and of Danish and Malaysian peripheral T-cell lymphomas (PTLs) and from tonsils of Danish infectious mononucleosis (IM). Our study showed that some of the 7 single-base mutations and the 30-bp deletion previously detected between codons of amino acid 322 and 366 in the BNLF-1 gene of the nasopharyngeal carcinoma cell line CAO were present in all Malaysian PTLs and in 60% of the Danish PTLs. In HD and the IM cases, the mutations were present in about 30%. The 30-bp deletion and the single base mutations occurred independently, and mutations were detectable in the majority of EBV type B-positive cases. These findings suggest that the 30-bp deletion and the 7 single-base mutations in the C-terminal part of the CAO-BNLF-1 gene do not characterize a new EBV type A substrain. Rather, some of the positions of single base mutations and the 30-bp deletion are hot spots that may have mutated independently through the evolution of EBV strains.

Matched MeSH terms: Herpesvirus 4, Human/genetics*; Herpesvirus 4, Human/isolation & purification
Fulltext Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma

Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N

N Engl J Med, 1995 Sep 14;333(11):693-8.
PMID: 7637746 DOI: 10.1056/NEJM199509143331103

BACKGROUND: The Epstein-Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV.
METHODS: EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The larger samples were also tested for the EBV genome with the use of Southern blotting. The expression of specific EBV RNAs was determined by the amplification of complementary DNA with the polymerase chain reaction.
RESULTS: Evidence of EBV infection was detected in all 11 tissue samples with dysplasia or carcinoma in situ. EBERs were identified in all eight samples tested, and LMP-1 was detected in all six of the tested samples. Six of the seven samples tested for the EBV termini contained clonal EBV DNA: Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were not detected.
CONCLUSIONS: Preinvasive lesions of the nasopharynx are infected with EBV. The EBV DNA is clonal, indicating that the lesions represent a focal cellular growth that arose from a single EBV-infected cell and that EBV infection is an early, possibly initiating event in the development of nasopharyngeal carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent infection but not the viral proteins that are characteristic of lytic infection. The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells suggests that its expression is essential for preinvasive epithelial proliferations associated with nasopharyngeal carcinoma.

Matched MeSH terms: Herpesvirus 4, Human/genetics*; Herpesvirus 4, Human/isolation & purification
p53 and nasopharyngeal carcinoma: a Malaysian study

Hoe SL, Lee ES, Khoo AS, Peh SC

Pathology, 2009;41(6):561-5.
PMID: 19900105

AIMS: Nasopharyngeal carcinoma (NPC) is a common malignancy among men in Malaysia. To determine the role of p53 in NPC, we screened for p53 mutations and evaluated the protein expression levels in samples from local patients with NPC.
METHODS: Fifty-three formalin-fixed, paraffin-embedded nasopharyngeal carcinoma tissue blocks were chosen for this study. The presence of Epstein-Barr virus (EBV) was determined by in situ hybridisation using an EBER probe. p53 protein expression was detected using immunohistochemistry. Simultaneously, amplifications by PCR were performed for p53 exons 5 to 8, followed by mutation screening via single strand conformation polymorphism (SSCP). Sequencing of all the four exons was performed in five samples with mobility shift. To rule out false negative results by SSCP, 13 samples with p53 overexpression and five samples with low p53 expression were randomly selected and sequenced.
RESULTS: There was no mutation found in exons 5 to 8 in all the samples despite 46 (87%) of them having high p53 levels. EBV was detected in 51 (96%) out of 53 samples. There was no statistically significant association between p53 expression level and EBV presence.
CONCLUSIONS: High-intensity staining for p53 by immunohistochemistry was common in our series of NPC tissue samples but was not associated with 'hot spot' mutations of exons 5-8 of the gene. We did not find a significant relationship between the expression level of p53 and presence of EBV. Our study confirms that mutation of the DNA-binding domain of p53 is rare in NPC.

Matched MeSH terms: Herpesvirus 4, Human/genetics; Herpesvirus 4, Human/isolation & purification
The role of CD30, CD40 and CD95 in the regulation of proliferation and apoptosis in classical Hodgkin's lymphoma

Kim LH, Eow GI, Peh SC, Poppema S

Pathology, 2003 Oct;35(5):428-35.
PMID: 14555388

AIMS: CD30, CD40 and CD95 are members of the tumour necrosis factor receptor superfamily. Ligation to their respective ligands (CD30L, CD40L, CD95L) will generate a diverse set of signalling cascades. We aim to study the expression pattern of CD30, CD40 and CD95 in classical Hodgkin's lymphoma (cHL) and to correlate the expressions with proliferation and apoptosis in the Hodgkin/Reed-Sternberg (H/RS) cells of cHL with or without associated Epstein-Barr virus (EBV) infection.
METHODS: A total of 66 cHL cases were retrieved from the archives. Expressions of CD30, CD40, CD95 and proliferation by Ki-67 expression were detected with an immunohistochemical staining method. Apoptosis index was assessed by in situ TUNEL staining technique on 30 randomly selected cases and the presence of EBV was determined by EBER in situ hybridisation.
RESULTS: Expression of CD30, CD40 and CD95 in the H/RS cells was observed in a high proportion of the cases (100, 93.9, 90.5%, respectively). There was no significant association or correlation of the expression of these molecules with the presence of EBV. Expression of CD40 was associated with expression of the proliferation marker Ki-67 (P=0.044), whereas strong (intermediate and high) expression of CD30 showed a significant correlation with proliferation in the EBV-negative cases only (P=0.025). No correlation was observed for the expression of CD30 and CD40 with apoptosis of the H/RS cells. The childhood cases showed weaker CD95 expression in the H/RS cells than the adult cases, and the expression of CD95 was weaker than that of CD40 in the childhood group.
CONCLUSIONS: Our results showed that CD30, CD40 and CD95 are highly expressed in the H/RS cells of the majority of cases of cHL. The expression patterns seem to be independent of EBV and do not correlate with apoptosis of the H/RS cells.

Matched MeSH terms: Herpesvirus 4, Human/genetics; Herpesvirus 4, Human/isolation & purification
On optimizing the blocking step of indirect enzyme-linked immunosorbent assay for Epstein-Barr virus serology

Lim CS, Krishnan G, Sam CK, Ng CC

Clin Chim Acta, 2013 Jan 16;415:158-61.
PMID: 23043757 DOI: 10.1016/j.cca.2012.08.031

Because blocking agent occupies most binding surface of a solid phase, its ability to prevent nonspecific binding determines the signal-to-noise ratio (SNR) and reliability of an enzyme-linked immunosorbent assay (ELISA).

Matched MeSH terms: Herpesvirus 4, Human/immunology; Herpesvirus 4, Human/isolation & purification*
Fulltext Epstein-Barr virus, the germinal centre and the development of Hodgkin's lymphoma

Mohamed G, Vrzalikova K, Cader FZ, Vockerodt M, Nagy E, Flodr P, et al.

J Gen Virol, 2014 Sep;95(Pt 9):1861-1869.
PMID: 24893782 DOI: 10.1099/vir.0.066712-0

The relationship between Epstein-Barr virus (EBV) and the germinal centre (GC) of the asymptomatic host remains an enigma. The occasional appearance of EBV-positive germinal centres in some patients, particularly those with a history of immunosuppression, suggests that EBV numbers in the GC are subject to immune control. The relationship, if any, between lymphoid hyperplasia with EBV-positive germinal centres and subsequent or concurrent lymphomagenesis remains to be clarified. As far as the development of EBV-associated Hodgkin's lymphoma is concerned, the suppression of virus replication, mediated by LMP1 on the one hand, and the loss of B-cell receptor signalling on the other, appears to be an important pathogenic mechanism. A further important emerging concept is that alterations in the microenvironment of the EBV-infected B-cell may be important for lymphomagenesis.

Matched MeSH terms: Herpesvirus 4, Human/immunology*
Clinical significance of plasma Epstein-Barr Virus DNA loads in a large cohort of Malaysian patients with nasopharyngeal carcinoma

Chai SJ, Pua KC, Saleh A, Yap YY, Lim PV, Subramaniam SK, et al.

J Clin Virol, 2012 Sep;55(1):34-9.
PMID: 22739102 DOI: 10.1016/j.jcv.2012.05.017

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr Virus (EBV)-associated cancer that is the fifth most common cancer in Malaysia. Early and accurate diagnoses are critical for patient prognosis. Unfortunately, early detection of NPC is still a challenge and the cost of more accurate imaging protocols is prohibitive in developing countries like Malaysia.

Matched MeSH terms: Herpesvirus 4, Human/genetics*
Fulltext High cell density and latent membrane protein 1 expression induce cleavage of the mixed lineage leukemia gene at 11q23 in nasopharyngeal carcinoma cell line

Yee PH, Sim SP

J Biomed Sci, 2010;17:77.
PMID: 20858288 DOI: 10.1186/1423-0127-17-77

Nasopharyngeal carcinoma (NPC) is commonly found in Southern China and South East Asia. Epstein-Barr virus (EBV) infection is well associated with NPC and has been implicated in its pathogenesis. Moreover, various chromosome rearrangements were reported in NPC. However, the underlying mechanism of chromosome rearrangement remains unclear. Furthermore, the relationship between EBV and chromosome rearrangement with respect to the pathogenesis of NPC has not been established. We hypothesize that during virus- or stress-induced apoptosis, chromosomes are initially cleaved at the base of the chromatin loop domain structure. Upon DNA repair, cell may survive with rearranged chromosomes.

Matched MeSH terms: Herpesvirus 4, Human/genetics
Novel Epstein-Barr virus immunoglobulin G-based approach for the specific detection of nasopharyngeal carcinoma

Abdulamir AS, Hafidh RR, Abu Bakar F, Abbas K

Am J Otolaryngol, 2010 Nov-Dec;31(6):410-7.
PMID: 20015794 DOI: 10.1016/j.amjoto.2009.06.006

PURPOSE: This study was designed to find a reliable Epstein-Barr virus (EBV) immunoglobulin (Ig) G-based diagnostic/screening test for nasopharyngeal carcinoma (NPC) able to demarcate between the NPC-related seropositivity of EBV IgG antibodies and that of other head and neck cancer (HNCA) and control groups. The NPC-associated immunosuppression affects EBV IgA much more than IgG, leading to inconsistent detection of NPC using EBV IgA antibodies.
MATERIALS AND METHODS: One hundred twenty-two HNCA patients, 42 NPC, 66 laryngeal carcinoma, and 14 hypopharyngeal carcinoma and 3 groups of 100 control subjects were enrolled in this study. Enzyme-linked immunosorbent assay (ELISA) was used to find a specific cutoff value for the NPC-related seropositivity of EBV IgG antibodies.
RESULTS: NPC group showed higher serum level of EBV IgG antibodies than control and other HNCA groups (P < .05). However, the traditional cutoff value, mean + 2 SDs of control subjects, failed to demarcate the seropositives of NPC patients from those of healthy population (P > .05). The new cutoff value, mean + 2 SDs of the seropositives group of control subjects who had already been grouped by the traditional cutoff value, proved successful. It succeeded to demarcate between the NPC-related EBV IgG seropositivity and that issued from the persistent, latent, or reactivated EBV infection in the population (P < .05). The sensitivity/specificity of NPC detection by the new cutoff-based ELISA kit, 76.19% and 86%, was close or higher than that of EBV IgA antibodies.
CONCLUSION: EBV IgG-based ELISA could be used for the diagnosis of NPC using a new cutoff threshold that excludes the population baseline of EBV IgG seropositivity.

Matched MeSH terms: Herpesvirus 4, Human/immunology*
Fulltext Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia

See HS, Yap YY, Yip WK, Seow HF

World J Surg Oncol, 2008;6:18.
PMID: 18275617 DOI: 10.1186/1477-7819-6-18

Nasopharyngeal carcinoma (NPC) is a human epithelial tumour with high prevalence amongst Chinese in Southern China and South East Asia and is associated with the Epstein-Barr virus (EBV). The viral genome harbours an oncogene, namely, the latent membrane protein 1 (LMP1) gene and known variants such as the 30-bp deletion and loss of XhoI restriction site have been found. Less is known about the relationship between these variants and the population characteristics and histological type.

Matched MeSH terms: Herpesvirus 4, Human/genetics*
Detection of Epstein-Barr virus in lower gastrointestinal tract lymphomas: a study in Malaysian patients

Yunos AM, Jaafar H, Idris FM, Kaur G, Mabruk MJ

Mol Diagn Ther, 2006;10(4):251-6.
PMID: 16884329

Many studies in the literature have shown that Epstein-Barr virus (EBV) is associated with several human lymphoid and epithelial malignancies. However, the prevalence of EBV in non-Hodgkin lymphoma (NHL) of the lower gastrointestinal (GI) tract has not been fully elucidated.

Matched MeSH terms: Herpesvirus 4, Human/isolation & purification*

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