The other side of the coin: Leveraging Epstein–Barr virus in research and therapy

Yu, F.; Tan, Wei Jian; Lu, Yanan; MacAry, Paul A.; Loh, Kwok Seng

doi:10.1016/j.oraloncology.2016.07.010

Cited by 3 publications

(2 citation statements)

References 73 publications

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“…Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus infecting more than 90% of the adult human population. As the first human oncogenic virus identified, it is well known to be associated with malignancies of both lymphoid and epithelial origins such as Burkkit's lymphoma, gastric cancer, and nasopharyngeal carcinoma (NPC) [1,2]. Following primary infection, EBV colonizes the memory B cell pool and establishes lifelong persistence as a latent infection [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Establishment of EBV latency in nasopharyngeal tumor epithelial cells by in vivo cell-mediated transfer infection

Yua¹,

Lu²,

Tay³

et al. 2018

Otorhinolaryngol Head Neck Sur

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Epstein-Barr virus (EBV) is a herpesvirus associated with approximately 1% of tumors worldwide. Although EBV is consistently detected in nasopharyngeal carcinoma(NPC) biopsy, it is hardly detected in normal nasopharyngeal epithelium. The mechanism how virus establishes latent infection in tumor epithelial cells, including the source of virus and the route of entry, has not been fully elucidated largely due to the lack of appropriate in vivo models. We herein aim to investigate the potential route that epithelial cells are infected with EBV. To this end, we established in vivo model system by injection of cell-free EBV or EBV producer line Akata cells together with EBV negative NPC line HONE-1 cells. Akin to in vitro infections, we presented the first in vivo evidence that cell-mediated transfer infection via Akata cells was much more efficient than cell-free virus. These cells then expressed the EBV latency-associated small RNA EBERs, but not lytic antigens, such as BZLF1. However, when cells were inoculated at separate sites, EBV producer line Akata cell failed to demonstrate the ability of migrating from distant location to interact with HONE-1 cell to establish latent infection. In conclusion, cell-cell contact is critical for in vivo EBV infection of nasopharyngeal epithelial cells.

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Section: Introductionmentioning

confidence: 99%

Establishment of EBV latency in nasopharyngeal tumor epithelial cells by in vivo cell-mediated transfer infection

Yua¹,

Lu²,

Tay³

et al. 2018

Otorhinolaryngol Head Neck Sur

Self Cite

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“…Thus, the development of novel compounds for molecular targeting should be a priority in cancer research. Among the various treatment modalities, traditional medicines with demonstrable antitumor activity are preferred 6 . The mechanism of activation of CDC2-cyclin B has been investigated extensively for use in chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Induction of Mitotic Delay in Pharyngeal and Nasopharyngeal Carcinoma Cells Using an Aqueous Extract of Ajuga bracteosa

Lin

Wang

et al. 2017

Int. J. Med. Sci.

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Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, for which radiotherapy and/or chemotherapy are the primary treatment methods. Many herbs are known to have potential uses in chemotherapy; however, the mechanisms underlying the observed antitumor activity of Ajuga bracteosa (AB) against NPC remain unclear. We explored the antitumor effects of AB, which was shown specifically to induce mitotic delay in pharyngeal (Detroit 562) and nasopharyngeal (Hone-1) cancer cells. Proliferation of cancer cells after exposure to aqueous extract of A. bracteosa (AEAB) was assessed using the MTT assay. DNA content and cell cycle arrest induction were analyzed using flow cytometry. The expression of checkpoint kinase 2 (CHK2), cell division control protein 2 (CDC2), and cyclin B1 was investigated using qRT-PCR and Western blot analysis. Results indicated the inhibition of cancer cell growth following exposure to AEAB. In addition, AEAB induced the accumulation of G2/M-phase cells in cancer cell through the disassociation of CDC2/cyclin B1 complex. Our findings suggested that, in addition to the known effects of AEAB in NPC prevention, it may have antitumor activities against NPC cells. In conclusion, AEAB inhibits the growth of and induces mitotic delay in cancer cells, supporting its use as an anticancer agent.

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Molecular and Clinical Characterization of a Founder Mutation Causing G6PC3 Deficiency

Zhen,

Betti,

Kars

et al. 2024

J Clin Immunol

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G6PC3 deficiency is a monogenic immunometabolic disorder that causes severe congenital neutropenia type 4. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Here, we investigated the origin and functional consequence of the G6PC3 c.210delC variant found in patients of Mexican descent. Based on the shared haplotypes amongst mutation carriers, we estimated that this variant originated from a founder effect in a common ancestor. Furthermore, by ancestry analysis, we concluded that it appeared in the indigenous Mexican population. At the protein level, we showed that this frameshift mutation leads to an aberrant protein expression in overexpression and patient-derived Epstein-Barr Virus-immortalized B (EBV-B) cells. The neutropenia observed in G6PC3-deficient patients is driven by the intracellular accumulation of the metabolite 1,5-anhydroglucitol-6-phosphate (1,5-AG6P) that inhibits glycolysis. We characterized how the c.210delC variant impacts glycolysis by performing extracellular flux assays on patient-derived EBV-B cells. When treated with 1,5-anhydroglucitol (1,5-AG), the precursor to 1,5-AG6P, patient cells exhibited markedly reduced engagement of glycolysis. Finally, we compared the clinical presentation of patients with the mutation c.210delC and all other G6PC3-deficient patients reported in the literature, and we found that the c.210delC carriers display all prominent clinical features observed in prior patients. In conclusion, G6PC3 c.210delC is a loss-of-function mutation that arose from a founder effect in the indigenous Mexican population. These findings may facilitate the diagnosis of additional patients in this geographical area. Moreover, the in vitro 1,5-AG-dependent functional assay used in our study could be employed to assess the pathogenicity of additional G6PC3 variants.

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The other side of the coin: Leveraging Epstein–Barr virus in research and therapy

Cited by 3 publications

References 73 publications

Establishment of EBV latency in nasopharyngeal tumor epithelial cells by in vivo cell-mediated transfer infection

Establishment of EBV latency in nasopharyngeal tumor epithelial cells by in vivo cell-mediated transfer infection

Induction of Mitotic Delay in Pharyngeal and Nasopharyngeal Carcinoma Cells Using an Aqueous Extract of Ajuga bracteosa

Molecular and Clinical Characterization of a Founder Mutation Causing G6PC3 Deficiency

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