Correction to: Latent Membrane Protein 1 Promotes Tumorigenesis Through Upregulation of PGC1β Signaling Pathway

Epstein-Barr virus-latent membrane protein 1 (EBV-LMP1) was associated with lymphoma, but its specific mechanism is still controversial. The study is aimed at studying the regulation of lymphoma resistance by EBV-LMP1 through the MEK1/2/Nrf-2 signaling pathway. First, LMP1 was knocked down in EBV-positive SNK-6 cells and overexpressed in EBV-negative KHYG-1 cells. First, we found that overexpression of LMP1 significantly promoted the resistance of KHYG-1 cells to cisplatin (DDP), which was related to increased autophagy in the cells. In contrast, knockdown of LMP1 expression in SNK-6 cells promoted cellular sensitivity to DDP and reduced the autophagy of cells after DDP treatment. Moreover, specific inhibition of autophagy in KHYG-1 cells significantly attenuated the resistance to DDP caused by overexpression of LMP1, but treatment with rapamycin in SNK-6 cells significantly promoted the autophagy in the cells. Subsequently, overexpression of LMP1 promoted the activation of the MEK1/2-Nrf2 pathway in KYHG-1 cells, whereas knockdown of LMP1 in SNK-6 cells inhibited the activation of the MEK1/2-Nrf2 pathway. Inhibition of MEK1/2/Nrf-2 blocked the promoting effects of LMP1 on lymphoma cell resistance. In conclusion, EBV-LMP1 promotes cell autophagy after DDP treatment by activating the MEK1/2/Nrf-2 signaling pathway in lymphoma cells, thus, enhancing the resistance of lymphoma cells to DDP.

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Latent Membrane Protein 1 of Epstein-Barr Virus Induces CD83 by the NF-κB Signaling Pathway

Journal of Virology ◽

10.1128/jvi.77.15.8290-8298.2003 ◽

2003 ◽

Vol 77 (15) ◽

pp. 8290-8298 ◽

Cited By ~ 36

Author(s):

Diana Dudziak ◽

Arnd Kieser ◽

Ulrike Dirmeier ◽

Falk Nimmerjahn ◽

Susanne Berchtold ◽

...

Keyword(s):

B Cells ◽

Membrane Protein ◽

Signaling Pathway ◽

Epstein Barr Virus ◽

Target Genes ◽

Latent Membrane Protein ◽

Luciferase Reporter ◽

Latent Membrane Protein 1 ◽

Barr Virus ◽

Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) infects human resting B cells and transforms them in vitro into continuously growing lymphoblastoid cell lines (LCLs). EBV nuclear antigen 2 (EBNA2) is one of the first viral proteins expressed after infection. It is able to transactivate viral as well as cellular target genes by interaction with cellular transcription factors. EBNA2 target genes can be studied easily by using an LCL (ER/EB2-5) in which wild-type EBNA2 is replaced by an estrogen-inducible EBNA2. Since the cell surface molecule CD83, a member of the immunoglobulin superfamily and a marker for mature dendritic cells, appeared on the surface of ER/EB2-5 cells within 3 h after the addition of estrogen, we analyzed the regulation of CD83 induction by EBV in more detail. Despite its rapid induction, CD83 turned out to be an indirect target gene of EBNA2. We could show that the viral latent membrane protein 1 (LMP1) is responsible for the induction of CD83 by using an LCL expressing a ligand- or antibody-inducible recombinant nerve growth factor receptor-LMP1 fusion protein. The inducibility of the CD83 promoter by LMP1 was mediated by the activation of NF-κB, as seen by use of luciferase reporter assays using the CD83 promoter and LMP1 mutants. Additionally, fusion constructs of the transmembrane domain of LMP1 and the intracellular signaling domain of CD40, TNF-R1, and TNF-R2 likewise transactivated the CD83 promoter via NF-κB. Our studies show that CD83 is also a target of the NF-κB signaling pathway in B cells.

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Sequence Variations of Epstein-Barr Virus-Encoded Small Noncoding RNA and Latent Membrane Protein 1 in Hematologic Tumors in Northern China

Intervirology ◽

10.1159/000510398 ◽

2021 ◽

Vol 64 (2) ◽

pp. 69-80

Author(s):

Hai-Yu Wang ◽

Lingling Sun ◽

Ping Li ◽

Wen Liu ◽

Zhong-Guang Zhang ◽

...

Keyword(s):

Membrane Protein ◽

Nested Pcr ◽

Noncoding Rna ◽

Epstein Barr Virus ◽

Northern China ◽

Latent Membrane Protein ◽

Latent Membrane Protein 1 ◽

Small Noncoding Rna ◽

Barr Virus ◽

Epstein Barr

Objective: To investigate the relationship between hematologic tumors and Epstein-Barr virus (EBV)-encoded small noncoding RNA (EBER) variations as well as latent membrane protein 1 (LMP1) variations. Methods: Patients with leukemia and myelodysplastic syndrome (MDS) were selected as subjects. Genotypes 1/2 and genotypes F/f were analyzed using the nested PCR technology, while EBER and LMP1 subtypes were analyzed by the nested PCR and DNA sequencing. Results: Type 1 was more dominant than type 2, found in 59 out of 82 (72%) leukemia and in 31 out of 35 (88.6%) MDS, while type F was more prevalent than type f in leukemia (83/85, 97.6%) and MDS (29/31, 93.5%) samples. The distribution of EBV genotypes 1/2 was not significantly different among leukemia, MDS, and healthy donor groups, neither was that of EBV genotypes F/f. EB-6m prototype was the dominant subtype of EBER in leukemia and MDS (73.2% [30/41] and 83.3% [10/12], respectively). The frequency of EB-6m was lower than that of healthy people (96.7%, 89/92), and the difference was significant (p < 0.05). China 1 subtype was the dominant subtype of LMP1 in leukemia and MDS (70% [28/40] and 90% [9/10], respectively), and there was no significant difference in the distribution of LMP1 subtypes among the 3 groups (p > 0.05). Conclusion: The distribution of EBV 1/2, F/f, EBER, and LMP1 subtypes in leukemia and MDS was similar to that in the background population in Northern China, which means that these subtypes may be rather region-restricted but not associated with leukemia and MDS pathogenesis.

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