Vascular lesion in a patient of chronic active Epstein-Barr virus infection with hypersensitivity to mosquito bites: vasculitis induced by mosquito bite with the infiltration of nonneoplastic Epstein-Barr virus-positive cells and subsequent development of natural killer/T-cell lymphoma with angiodestruction

This report describes a vasculitis and subsequently developing angiodestructive lymphoma in an 11-year-old Japanese-Filipino girl exhibiting mosquito allergy with the background of chronic active Epstein-Barr virus (EBV) infection. She developed necrotic skin ulcer at the site of mosquito bite, and histopathological examination revealed EBV-positive mononuclear cell infiltration throughout the wall of small-sized muscular artery. These EBV-positive lymphoid cells were oligoclonal in Southern blot analysis for EBV terminal repeats. Effectiveness of steroid therapy also supports the nonneoplastic nature. Approximately 1 year later, she developed progressive large skin ulcer without mosquito bites. Microscopically, the angiocentric or angiodestructive pattern of EBV-positive atypical cells supported the diagnosis of extranodal natural killer/T-cell lymphoma. Southern blot analysis revealed the monoclonal neoplastic nature of EBV-positive cells. In contrast to the primary mosquito bite lesion, natural killer/T-cell lymphoma cells exhibited the higher expression of EBV latent membrane protein 1 mRNA and the apparent protein expression detected by immunohistochemistry.     

Sensitivity and specificity of Epstein-Barr virus IGA titer in the diagnosis of nasopharyngeal carcinoma: a three-year institutional review

BACKGROUND: IgA antibody titers to the Epstein-Barr virus (EBV) viral capsid antigen (EBV IgA-VCA) and to the EBV early antigen (EBV IgA-EA) are used to screen for nasopharyngeal carcinoma (NPC). This study evaluates the sensitivity and specificity of EBV IgA-VCA and EBV IgA-EA titers in screening patients for NPC and in those diagnosed with NPC at our institution. METHODS: The NPC status was determined for all patients who had their EBV IgA-VCA and EBV-IgA EA titers measured over a 3-year period, and the sensitivity and specificity were calculated. RESULTS: Five thousand one hundred ninety-six samples were analyzed. NPC was diagnosed in 215 patients. The sensitivity and specificity of a raised EBV IgA-VCA titer (> or =1:5) for diagnosing NPC were 89% and 80%, respectively, with a raised EbV IgA-EA titer (> or =1:5) having a sensitivity and specificity of 63% and 97%, respectively. CONCLUSIONS: Although the EBV IgA-VCA titer is sensitive for the diagnosis of NPC, it should not be used as the sole means of screening for NPC in a population in which NPC is endemic.     

Prevalence of LMP-1 gene in tonsils and non-neoplastic nasopharynxes by nest-polymerase chain reaction in Taiwan

BACKGROUND: The purpose of this study was to investigate the frequency of Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) in tonsils and non-neoplastic nasopharynxes in Taiwan. METHODS: Nest-polymerase chain reaction (nest-PCR) was used to examine the presence of LMP-1 gene in lymphoid hyperplasia from non-neoplastic tonsillar and nasopharyngeal tissues and in tonsillar cancers. RESULTS: In 152 cases, 64 biopsy tissues were obtained from lymphoid hyperplasia of nasopharynxes, 57 from tonsillectomy of non-neoplastic tonsils, and 31 from tonsillar cancers. LMP-1 was detected in 43.4% of the study group. Nineteen (29.7%) and 29 (50.9%) lymphoid hyperplasias from normal nasopharynxes and tonsils, respectively, and 18 (58.1%) biopsies from tonsillar cancers had positive LMP-1. The 30-base pair (bp) deleted variant was detected in 89.5% and 82.8% of normal nasopharynxes and tonsils, respectively, and in 66.7% of biopsies from tonsillar cancers (p =.198). CONCLUSION: This study found that the 30-bp variant was the predominant type of LMP-1 from a healthy population in Taiwan.     

Increased numbers of CD38 molecules on bright CD8+ T lymphocytes in infectious mononucleosis caused by Epstein-Barr virus infection

The aim of this study was to quantify the expression of CD38 on CD8+ T lymphocytes of patients with infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) and cytomegalovirus (CMV). CD38 quantification technique chosen for this study was based on the enumeration of CD38 antibody binding sites in comparison to the quantification standards rather than determining relative fluorescence, which is difficult to standardize. The study enrolled 19 patients with typical clinical and laboratory parameters compatible with EBV-induced IM as well as 10 patients with atypical clinical presentation of this disease. Furthermore, CD38 expression was analysed in a group of 13 patients with IM caused by CMV infection. CD38 quantification was performed within 6 days of the presentation of symptoms. All three groups of IM patients showed a statistically significant increase in the number of anti-CD38 antibody binding sites (which correspond to the number of CD38 molecules) on bright CD8+ T lymphocytes compared to healthy controls. The numbers of CD38 molecules expressed on CD8+ T lymphocytes did not differ significantly between IM patients with typical and atypical clinical presentation of the disease. Patients with CMV-induced IM had significantly lower numbers of CD38 molecules expressed on CD8+ T lymphocytes. Therefore, we conclude that CD38 quantification could be helpful in differential diagnostics of IM cases with atypical clinical presentation.     

EBV-encoded EBNA-5 associates with P14ARF in extranucleolar inclusions and prolongs the survival of P14ARF-expressing cells

Epstein-Barr virus (EBV) carrying lymphoblastoid cells of normal origin express the full program of all 9 virus-encoded, growth transformation associated proteins. They have an intact p53 pathway as a rule. This raises the question of whether any of the viral proteins impair the pathway functionally. Using a yeast 2-hybrid system, we have shown that EBNA-5 but not the other EBNAs interacts with the p14ARF protein, a regulator of the p53 pathway. The interaction was confirmed in vitro using a GST pull-down assay. Moreover, expression of EBNA-5 increased the survival of p14ARF-transfected cells. EBV infection of resting B cells induced the expression of p14ARF mRNA without increased level of the protein. A fraction of the p14ARF localized to the nucleoli but the bulk of the protein accumulated in nuclear but extranucleolar inclusions. Formation of the extranucleolar inclusions led to complete relocalization of EBNA-5 from nucleoplasm to these structures. The inclusions also contained p53 and HDM2, and were surrounded by PML bodies and proteasomes, which suggests that these inclusions could be targets for proteasome dependent protein degradation.     

EBV-LMP1对鼻咽癌细胞系CNE1细胞转移相关因素的影响

背景与目的:已证实EB病毒(Epstein-Barrvirus,EBV)编码的潜伏膜蛋白1(latentmembraneprotein1,LMP1)能够诱导鼻咽癌细胞中基质金属蛋白酶9(matrixmetalloproteinase-9,MMP-9)的表达。本实验的目的是观察EB病毒潜伏膜蛋白1(EBV-LMP1)对鼻咽癌细胞系CNE1细胞转移相关因素的影响,探讨LMP1在鼻咽癌侵袭、转移过程中的作用。方法:用免疫组化法及Westernblot法检测CNE1-GL(转染LMP1基因的CNE1细胞)和CNE1细胞中MMP-9的表达情况;用细胞-基质粘附实验、细胞运动实验和肿瘤细胞重组基底膜侵袭实验检测LMP1对CNE1细胞粘附、运动及侵袭能力的影响。结果:免疫组化法及Westernblot法结果均显示CNE1-GL细胞中MMP-9的表达明显高于CNE1细胞(P<0.05);肿瘤细胞-基质粘附实验结果显示,CNE1-GL的粘附能力(平均吸光度值为1.2508±0.0711),高于CNE1细胞(平均吸光度值为0.9519±0.068),两者相比差异有显著性(P<0.01)。运动实验及重组基底膜侵袭实验结果均显示,穿过游离的聚乙烯吡咯烷酮膜(polyvinylpyrroli-done-free,PVP-F)的CNE1-GL细胞数明显高于CNE1细胞(P<0.01)。结论:LMP1能够诱导CNE1细胞中MMP-9的表达,且增强CNE1细胞与基底膜的粘附能力、运动能力及侵袭能力。