EBV-Associated Cancer and Autoimmunity: Searching  for Therapies

Capone, Giovanni; Fasano, Candida; Lucchese, Guglielmo; Calabrò, Michele; Kanduc, Darja

doi:10.3390/vaccines3010074

Cited by 15 publications

(12 citation statements)

References 97 publications

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“…Viruses are obligate intracellular parasites, and their replication cycles depend on some host cell factors. For example, some studies suggested that cellular origin recognition complex (ORC) and minichromosome maintenance (MCM) complex are related to the DS element of oriP, implicating them in the initiation of EBV DNA replication (Frappier, 2012a;Capone et al, 2015). These host factors may also be potential targets for antiviral therapy.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus Nuclear Antigen 1 Recruits Cyclophilin A to Facilitate the Replication of Viral DNA Genome

Xin

Liu

et al. 2019

Front. Microbiol.

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Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)-mediated DNA episomal genome replication and persistence are essential for the viral pathogenesis. Cyclophilin A (CYPA) is upregulated in EBV-associated nasopharyngeal carcinoma (NPC) with unknown roles. In the present approach, cytosolic CYPA was found to be bound with EBNA1 into the nucleus. The amino acid 376-459 of the EBNA1 domain was important for the binding. CYPA depletion attenuated and ectopic CYPA expression improved EBNA1 expression in EBV-positive cells. The loss of viral copy number was also accelerated by CYPA consumption in daughter cells during culture passages. Mechanistically, CYPA mediated the connection of EBNA1 with oriP (origin of EBV DNA replication) and subsequent oriP transcription, which is a key step for the initiation of EBV genome replication. Moreover, CYPA overexpression markedly antagonized the connection of EBNA1 to Ubiquitinspecific protease 7 (USP7), which is a strong host barrier with a role of inhibiting EBV genome replication. The PPIase activity of CYPA was required for the promotion of oriP transcription and antagonism with USP7. The results revealed a strategy that EBV recruited a host factor to counteract the host defense, thus facilitating its own latent genome replication. This study provides a new insight into EBV pathogenesis and potential virus-targeted therapeutics in EBV-associated NPC, in which CYPA is upregulated at all stages.

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Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus Nuclear Antigen 1 Recruits Cyclophilin A to Facilitate the Replication of Viral DNA Genome

Xin

Liu

et al. 2019

Front. Microbiol.

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“…Latent EBV infection is implicated in the etiology of several malignancies . Also, EBV is associated with autoimmune diseases, systemic lupus erythematosus (SLE), hemophagocytic lymphohistiocytosis (HLH), rheumatoid arthritis (RA), and multiple sclerosis (MS) …”

Section: Introductionmentioning

confidence: 99%

S‐S‐PEG‐COOH Self‐Assembled Monolayer on Gold Surface Enabled a Combined Assay for Serological EBV Antibody Isotypes

Liu

et al. 2018

Proteomics Clinical Apps

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Purpose: Epstein-Barr virus (EBV) is a ubiquitous human gamma herpes virus that infects human epithelial cells and B lymphocytes. It would be potentially valuable to develop novel combined assays to benefit screening for large panels of samples of EBV infectious diseases. Experimental design: A simple antigen-probed biochip that is modified with S-S-PEG-COOH and is used as a label-free high-throughput screening method for a combined detection of EBV capsid antigen IgM antibody, capsid antigen IgG antibody, and nuclear antigen IgG antibody.Results: This protein biochip has similar feasibility, sensitivity, and specificity in comparison with Liaison chemiluminescent immunoassay (CLIA). Detection limit of the EBV antibodies by the biochip is almost identical to that by CLIA-L (2.91 U mL -1 vs 3.00 U mL -1 for EBNA-1 IgG, 8 U mL -1 vs10 U mL -1 for EBV-VCA IgG, and 3.5 U mL -1 vs 10 U mL -1 for EBV-VCA IgM). Tests of the three serological antibodies against EBV by the biochip are consistent with the CLIA-L method in 274 clinical sera, respectively. Finally, the combined biochip is successfully utilized for diagnostic identification of EBV infection in 14 patients with infectious mononucleosis (IM) and 25 patients with systemic lupus erythematosus SLE, as well as additional 10 known real-time PCR positive patients.

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“…The association of EBV and HL was first asserted during the researches regarding the etiology of BL in 1964 21 . In the later years, it was determined that EBV played a role in the etiology of many malignant diseases like BL, nasopharynx carcinoma, HL and B-cell lymphoma in immunodeficiency disorders 22,23 . Significant differences were detected between the association of EBV with endemic (African type) and sporadic BL.…”

Section: Discussionmentioning

confidence: 99%

Pediatrik lenfomalarda histopatolojik subtip ve Ebstein-Barr virus ilişkisi: immünohistokimyasal ve in situ hibridizasyon çalışması

Bağır

Acikalin

Ergïn

et al. 2018

Cukurova Medical Journal

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AbstractÖz Purpose: The aim of this study was toexplore the histopathologic subtypes of pediatric lymphomas and their relation with Ebstein-Barr virus infection in our region. Materials and Methods:In this retrospective study, 87 children including 36 cases with Hodgkin lymphoma and 51 cases with non-Hodgkin lymphoma were included in the study. The pathologic slides were used to investigate immunohistochemical staining with ebstein-barr virüs latent membrane protein-1 and in-situ hybridization. Results:The most common histopathological subtype in hodgkin lymphoma cases was mixed cellular classical hodgkin lymphoma (55.6%). The most common histopathological subtype in Non-Hodgkin lymphoma cases was Burkitt lymphoma (51.0%). Ebstein-Barr virüs latent membrane protein-1 was positive in 29 Hodgkin lymphoma. All non-Hodgkin lymphoma cases were stained negative with ımmunohistochemical. The positive staining rate of Hodgkin lymphoma cases with in-situ hybridization was 83.3% and this rate was 27.5% in nonHodgkin lymphoma cases. The differences between groups for both staining methods were significant. Conclusion:The results of this study show that the distribution of histopatholojik subtypes of pediatric lymphomas similar to in developing countries. And we have observed that in-situ hybridization is more specific than immunohistochemistry because Ebstein-Barr virus positivity is more detected in in-situ hybridization.Amaç: Bu çalışmanın amacı bölgemizdeki pediatrik lenfomaların histopatolojik alt tiplerinin oranını ve bunların Ebstein-Barr virüs enfeksiyonu ile olan ilişkisini incelemektir. Gereç ve Yöntem: Hodgkin lenfoma tanısı alan 36 olgu ve non-hodgkin lenfoma tanısı alan 51 olgu retrospektif arşiv taraması yapılarak çalışmaya dahil edildi. Olgulara immünohistokimyasal olarak Ebstein-Barr virüs latent membran proteini-1 ve in-situ hibridizasyon uygulandı. Bulgular: Hodgkin lenfoma olgularında; en sık rastlanan histopatolojik alt tipler sırası ile mikst sellüler klasik hodgkin lenfoma (%55,6) idi. Non-Hodgkin lenfoma olgularında en sık rastlanan histopatolojik alt tip Burkitt lenfoma (%51) idi. Ebstein-Barr virüs latent membran proteini-1 ile 29 hodgkin lenfoma olgusunda pozitif iken non-hodgkin lenfoma olgularında immünohistokimya ile pozitif boyanma saptanmadı. Hodgkin lenfoma olgularında in situ hibridizasyon ile boyanma oranı % 83.,3 iken nonHodgkin lenfoma olgularında bu oran % 27.5 idi.. Her iki boyama yöntemi için gruplar arasındaki fark istatistiksel olarak anlamlıydı. Sonuç: Bu çalışmada, olgularımızın histopatolojik dağılımlarının gelişmekte olan ülkelerdeki pediatrik lenfoma olguları ile benzer olduğunu göstermektedir. Aynı zamanda in situ hibridizasyon'da Ebstein-Barr virüs pozitifliği daha fazla olması nedeniyle in situ hibridizasyonun ebstein barr virüs tespitinde immünohistokimyadan daha spesifik olduğunu düşünmekteyiz.

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EBV-Associated Cancer and Autoimmunity: Searching for Therapies

Cited by 15 publications

References 97 publications

Epstein-Barr Virus Nuclear Antigen 1 Recruits Cyclophilin A to Facilitate the Replication of Viral DNA Genome

Epstein-Barr Virus Nuclear Antigen 1 Recruits Cyclophilin A to Facilitate the Replication of Viral DNA Genome

S‐S‐PEG‐COOH Self‐Assembled Monolayer on Gold Surface Enabled a Combined Assay for Serological EBV Antibody Isotypes

Pediatrik lenfomalarda histopatolojik subtip ve Ebstein-Barr virus ilişkisi: immünohistokimyasal ve in situ hibridizasyon çalışması

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