• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.15 no.1
• /
• pp.38-43
• /
• 2012

Purpose: Epstein-Barr virus (EBV) hepatitis is a usually asymptomatic and self-limiting disease in immunocompetent patients. However, the range of severity is wide, and the serological diagnosis is typically difficult until the convalescent phase. Thus, we examined the value of plasma EBV DNA real-time quantitative polymerase chain reaction (RT-qPCR) in EBV hepatitis for the timely diagnosis and the relationship between EBV viral load and clinical severity. Methods: Sixty samples were confirmed as having EBV infection by RT-qPCR with the EBV BALF5 gene sequence. We examined the clinical characteristics of EBV hepatitis by reviewing medical records. Results: The median total duration of fever was 8 days (range: 0-13 days). The mean peak value of aspartate aminotransferase (AST) was $241{\pm}214$ U/L, and the mean peak value of alanine aminotransferase (ALT) was $298{\pm}312$ U/L. There was no correlation between the serum levels of liver enzyme and plasma EBV DNA titer ($p$=0.1) or between median total duration of fever and EBV DNA titer ($p$=0.056). The median age of the EBV VCA IgM-negative group was lower compared with the EBV VCA IgM-positive group in EBV hepatitis (2 years vs. 6 years, $p$=0.0009). Conclusion: The severity of EBV hepatitis does not correlate with circulating EBV DNA load according to our data. Furthermore, we suggest that plasma EBV PCR may be valuable in young infants in whom the results of serology test for EBV infection commonly are negative.

• The Journal of the Korean dental association
• /
• v.48 no.5
• /
• pp.365-370
• /
• 2010

Herpes virus family is highly infectious to patients, their families and dentists. The diagnosis of herpes infection is based on the characteristic clinical appearance and the location of the lesions. Herpes Simplex Virus(HSV) usually acquired through direct contact with infected lesions or body fluids, and the prevalence of HSV infection increases progressively from childhood. Primary infections provoke herpetic gingivostomatis typically affects the tongue, lips, gingival, buccal mucosa and palate. Recurrent infections give rise to vesiculo-ulcerative lesions at vermilion border of lip(herpes labialis). In the form of chickenpox, Varicella Zoster Virus(VZV) usually is infected in childhood. VZV spreads in the affected primary afferent nerve to the skin and produces a vesicular rash and pain. Epstein-Barr Virus(EBV) infects B cells and cause infectious mononucleosis. Latent EBV infection has also been implicated in Burkitt lymphoma, nasopharyngeal carcinoma. Cytomegalovirus(CMV) is associated with immune-compromised patient such as organ transplantation and AIDS patients.

• Biomolecules & Therapeutics
• /
• v.19 no.4
• /
• pp.398-410
• /
• 2011

Over the past few decades, our understanding of the epidemiology and immunopathogenesis of Hodgkin lymphoma (HL) has made enormous advances. Consequently, the treatment of HL has changed significantly, rendering this disease of the most curable human cancers. To date, about 80% of patients achieve long-term disease-free survival. However, therapeutic challenges still remain, particularly regarding the salvage strategies for relapsed and refractory disease, which need further identification of better prognostic markers and novel therapeutic schemes. Although the precise molecular mechanism by which Epstein-Barr virus (EBV) contributes to the generation of malignant cells present in HL still remains unknown, current increasing data on the role of EBV in the pathobiology of HL have encouraged people to start developing novel and specific therapeutic strategies for EBV-associated HL. This review will provide an overview of therapeutic approaches for acute EBV infection and the classical form of HL (cHL), especially focusing on EBV-associated HL cases.

• Clinical and Experimental Pediatrics
• /
• v.57 no.10
• /
• pp.457-460
• /
• 2014

A flaccid tetraparesis in Bickerstaff's brainstem encephalitis (BBE) is presumed to be a sign of overlapping Guillain-Barr$\acute{e}$ syndrome (GBS). In addition, BBE and Fisher syndrome, which are clinically similar and are both associated with the presence of the immunoglobulin G anti-GQ1b antibody, represent a specific autoimmune disease with a wide spectrum of symptoms that include ophthalmoplegia and ataxia. A 2-year-old boy presented with rapidly progressive ophthalmoplegia, ataxia, hyporeflexia, weakness of the lower extremities, and, subsequently, disturbance of consciousness. He experienced bronchitis with watery diarrhea and had laboratory evidence of recent infection with Epstein-Barr virus (EBV). He was diagnosed as having overlapping GBS and BBE associated with EBV and received treatment with a combination of immunoglobulin and methylprednisolone, as well as acyclovir, and had recovered completely after 3 months. In addition, he has not experienced any relapse over the past year. We suggest that combinations of symptoms and signs of central lesions (disturbance of consciousness) and peripheral lesions (ophthalmoplegia, facial weakness, limb weakness, and areflexia) are supportive of a diagnosis of overlapping GBS and BBE and can be helpful in achieving an early diagnosis, as well as for the administration of appropriate treatments.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.2285-2289
• /
• 2016

Background: Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly is an entity introduced in the latest WHO classification of lymphoid tumors and defined in patients older than 50 years without prior lymphoma or immunodeficiency. However, recently it has also been seen in patients under 50. There is thus debate as to whether these are separate entities. Materials and Methods: In this retrospective study, we analyzed de novo DLBCL admitted to our institute over a period of two years. Clinical data included age, sex, nodal and extranodal presentation. The results of an immunohistochemistry (IHC) panel were also reviewed. IHC findings were mainly used to sub-classify DLBCL as germinal center vs. non germinal center types. IHC for identification of LMP-1 (latent membrane protein) and in situ hybridization for detection of EBV-encoded RNA (EBER) was performed. EBV prevalence, clinical data and IHC findings were compared between patients under and over 50 years of age. Results: Out of 95 DLBCL, 11.6% were EBV positive (7.5% and 14.5% in the young and old groups). We did not find any significant differences in IHC subclasses and clinical data between EBV positive DLBCL (EBV+DLBCL) of young and old groups. Conclusions: EBV+DLBCL are not exclusive to patients older than 50 years. With regard to clinical data as well as IHC subclasses, no differences were evident between EBV+DLBCL of young and old groups. Our suggestion is to eliminate any cut off age for EBV+DLBCL.

• Molecules and Cells
• /
• v.39 no.4
• /
• pp.286-291
• /
• 2016

Epstein-Barr virus (EBV) is the prototypical ${\gamma}$-herpesvirus and an obligate human pathogen that infects mainly epithelial cells and B cells, which can result in malignancies. EBV infects these target cells by fusing with the viral and cellular lipid bilayer membranes using multiple viral factors and host receptor(s) thus exhibiting a unique complexity in its entry machinery. To enter epithelial cells, EBV requires minimally the conserved core fusion machinery comprised of the glycoproteins gH/gL acting as the receptor-binding complex and gB as the fusogen. EBV can enter B cells using gp42, which binds tightly to gH/gL and interacts with host HLA class II, activating fusion. Previously, we published the individual crystal structures of EBV entry factors, such as gH/gL and gp42, the EBV/host receptor complex, gp42/HLA-DR1, and the fusion protein EBV gB in a postfusion conformation, which allowed us to identify structural determinants and regions critical for receptor-binding and membrane fusion. Recently, we reported different low resolution models of the EBV B cell entry triggering complex (gHgL/gp42/HLA class II) in "open" and "closed" states based on negative-stain single particle electron microscopy, which provide further mechanistic insights. This review summarizes the current knowledge of these key players in EBV entry and how their structures impact receptor-binding and the triggering of gB-mediated fusion.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.17 no.1
• /
• pp.57-60
• /
• 2014

Acute acalculous cholecystitis (AAC) is an inflammation of the gallbladder in the absence of demonstrated stones. AAC is frequently associated with severe systemic inflammation. However, the exact etiology and pathogenesis of AAC still remain unclear. Acute infection with Epstein Barr virus (EBV) in childhood is usually aymptomatic, whereas it often presents as typical infectious mononucleosis symptoms such as fever, cervical lymphadenopathy, and hepatosplenomegaly. AAC may occur during the course of acute EBV infection, which is rarely encountered in the pediatric population. AAC complicating the course of a primary EBV infection is usually associated with a favorable outcome. Most of the patients recover without any surgical treatment. Therefore, the detection of EBV in AAC would be important for prediction of better prognosis. We describe the case of a 10-year-old child who presented with AAC during the course of primary EBV infection, the first in Korea, and review the relevant literature.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.23
• /
• pp.10489-10493
• /
• 2015

Background: Gastric cancer is the second most common gastrointestinal cancer and is largely attributed to Helicobacter pylori (H. pylori) infection. In addition, studies have also shown association with Epstein-Barr virus (EBV) in 10% of gastric cancers. This study assessed the characteristics of EBV associated gastric cancers (EBVaGC) in Brunei Darussalam. Materials and Methods: This study included gastric cancers diagnosed between 2008 and 2012, registered with the Department of Pathology RIPAS Hospital, Brunei Darussalam. Clinical case notes were systematically reviewed. Histology specimens were all stained for EBV and also assessed for intestinal metaplasia and H. pylori. Results: There were a total of 81 patients (54 male and 27 females) with a mean age of $65.8{\pm}14.8years$ included in the study. Intestinal metaplasia and active H. pylori infection were detected in 40.7% and 30.9% respectively. A majority of the tumors were proximally located (55.6%), most poorly differentiated (well differentiated 16%, moderately differentiated 30.9% and poorly differentiated 53.1%) and the stages at diagnosis were; stage I (44.4%), stage II (23.5%), stage III (8.6%) and stage IV (23.5%). EBV positivity (EBVaGC) was seen in 30.9%. Between EBVaGC and EBV negative gastric cancers, there were no significant differences (age, gender, ethnic group, presence of Intestinal metaplasia, tumor locations, stages of disease and degree of tumor differentiation). Conclusions: This study showed that a third of gastric cancers in Brunei Darussalam were positive for EBV, higher than what have been reported in the literature. However, there were no significant differences between EBVaGC and EBV negative gastric cancers. This suggests that the role of EBV in gastric cancer may be mostly incidental rather than any causal relation. However, further studies are required.

• Journal of Microbiology
• /
• v.41 no.2
• /
• pp.129-136
• /
• 2003

The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMPI) exhibits considerable sequence heterogeneity among EBV isolates. Seven distinct EBV strains have been defined based on sequence polymorphisms in the LMPI gene, which are designated China 1, China 2, China 3, Alaskan, Mediterranean, NC, and the B95-8 strains. In this study, we analyzed a 30-bp deletion and sequence variations in the carboxy-terminal region of the LMPl gene in 12 EBV isolates from spontaneous lym-phoblastoid cell lines derived from individuals with non-EBV associated cancers in Korea. Eleven of the 12 isolates showed a 30-bp deletion spanning LMPI amino acids 342 to 353, suggesting a high prevalence of the LMPI 30-bp deletion variant among EBV isolates in Korea. In addition, all 12 isolates had a 15-bp common deletion in the 33-bp repeat region and multiple base-pair changes relative to the prototype B95-8 EBV strain along with variations in the number of the 33-bp repeats. The bp changes at positions 168746, 168694, 168687, 168395, 168357, 168355, 168631, 168320, 168308, 168295, and 168225 were highly conserved among the isolates. Comparative analysis of sequence change patterns in the LMPI carboxy-terminal coding region identified nine 30-bp deletion variants as China 1, two deletion variants as a possible interstrain between the Alaskan and China 1 strains, and a single undeleted variant as a possible variant of the Alaskan strain. These results suggest the predominance of the China 1 EBV strain in the Korean population.

• BMB Reports
• /
• v.49 no.4
• /
• pp.226-231
• /
• 2016

Epstein Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) plays a pivotal in an EBV episome replication and persistence. Despite considerable attempts, there are no EBV drugs or vaccines. We attempted to eradicate EBV episomes by targeting EBNA1 using the transcription activator-like effector nucleases (TALEN) (E1TN). E1TN-mediated transient knockout (KO) of EBNA1 reduced EBNA1 expression, and caused significant loss of EBV genomes and progressive death of EBV-infected cells. Furthermore, when a mixture of EBV-infected Burkitt's lymphoma (BL) cells and EBV-negative BL cells was targeted by E1TN, EBV-negative cells were counter-selected while most EBV-infected cells died, further substantiating that EBNA1 KO caused selective death of EBV-infected cells. TALEN-mediated transient targeting of EBNA1 attenuated the growth of EBV-infected cells, implicating a possible therapeutic application of E1TN for EBV-associated disorders.