TheLMP1 gene isolated from Russian nasopharyngeal carcinoma has no 30-bp deletion

Hahn, Peter; Novikova, Elena L.; Scherback, L.; Janik, Constantin; Pavlish, O; Arkhipov, Viktor; Nicholls, John M.; Müller-Lantzsch, N.; Gurtsevitch, Vladimir; Grässer, Friedrich A.

doi:10.1002/1097-0215(200002)9999:9999<::aid-ijc1122>3.0.co;2-w

Cited by 36 publications

(27 citation statements)

References 17 publications

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“…Similar substitution within the DG-SXXS motif in I B␣ abrogated the ability of I B␣ to recruit ␤-TrCP/HOS (66). Furthermore, substitutions of Ser-366 (such as S366T, S366A, and S366N) are observed more frequently in LMP1 isolates from EBV-associated tumors than in LMP1 from peripheral blood lymphocytes from apparently healthy individuals (30,39,65,67,68). G212S mutation may not be as common as substitution of Ser-366 (65, 67).…”

Section: Discussionmentioning

confidence: 94%

“…We did not find this substitution in many German or Russian LMP1 isolates that contained the S366T mutation. On the other hand, none of the described cases has revealed the presence of the LMP1-95-8 identical isolate in tumor tissue of any EBV-associated disease (39). 4 These data imply that, in tumorigenesis, LMP1 is under selective pressure to diminish its ability to interact with HOS and thus to abandon restrictions on activating NF-B signaling.…”

Section: Discussionmentioning

confidence: 98%

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Interaction of Epstein-Barr Virus Latent Membrane Protein 1 with SCFHOS/β-TrCP E3 Ubiquitin Ligase Regulates Extent of NF-κB Activation

Tang

Pavlish

Spiegelman³

et al. 2003

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 98%

Interaction of Epstein-Barr Virus Latent Membrane Protein 1 with SCFHOS/β-TrCP E3 Ubiquitin Ligase Regulates Extent of NF-κB Activation

Tang

Pavlish

Spiegelman³

et al. 2003

Journal of Biological Chemistry

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“…However, this notion has recently been challenged by the fact that virus with a deleted version of LMP-1 is present in the general population in endemic regions, but can also be found in non-endemic areas within Asia (Itakura et al, 1996) and in western countries (Sandvej et al, 1997). Moreover, it has been shown that the LMP-1 gene from non-endemic Russian NPC harbours a nondeleted version of LMP-1, whereas the gene with a deletion can be found in healthy subjects from the same area (Hahn et al, 2001). Therefore, we postulate that if highly tumorigenic EBV strains do exist, they would be found preferentially in consistently EBV-associated tumours, such as NPC, and differ significantly from the strains present in other, non-neoplastic counterparts of the same anatomical sites.…”

Section: Discussionmentioning

confidence: 99%

Amino acid changes in functional domains of latent membrane protein 1 of Epstein–Barr virus in nasopharyngeal carcinoma of southern China and Taiwan: prevalence of an HLA A2-restricted ‘epitope-loss variant’

Lin

Cherng²,

Lin³

et al. 2004

Journal of General Virology

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Full-length sequences of the Epstein-Barr virus (EBV) gene for latent membrane protein (LMP)-1 from 22 nasopharyngeal carcinoma (NPC) biopsy specimens and 18 non-neoplastic counterparts (NPI) were determined. Relative to the B95-8 strain, the amino acid sequences of the toxic-signal and transformation domains were changed variably in NPC and NPI specimens; in contrast, no change was observed in the NF-kB (nuclear factor kB) activation domain. HLA typing revealed that 47 % of NPC and 31 % of NPI specimens were HLA A2-positive. A major A2-restricted epitope within LMP-1 (residues 125-133) was analysed. At residue 126, a change of LRF was detected in 91 % (20/22) of NPC and 67 % (12/18) of NPI specimens. In addition, a deletion at residue 126 was detected in one NPC sample from Taiwan. At residue 129, a change of MRI was observed in all samples, regardless of whether they were NPC or NPI. The changes in this peptide between NPC and NPI specimens, including mutation and deletion, are statistically significant (P<0?05). A recent report indicated that this variant sequence is recognized poorly by epitope-specific T cells. Genotyping results indicated that 96 % of NPC and 67 % of NPI samples carried a type A virus. By scanning the entire sequence of LMP-1, eight distinct patterns were identified. Detailed examination of these patterns revealed that type A strains are more prevalent in NPC than in NPI specimens and are marked by the loss of an XhoI site, the presence of a 30 bp deletion and the presence of a mutated, A2-restricted, T cell target epitope sequence. These results suggest that an EBV strain carrying an HLA A2-restricted 'epitope-loss variant' of LMP-1 is prevalent in NPC in southern China and Taiwan.

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“…by the viral oncogene LMP1 42 in the presence or absence of NP9 and found no effect (data not shown). The expression of NP9 protein was analysed in the Burkitt's lymphoma cell line Raji and the human lymphoblastoid cell line IB4.…”

Section: Infectious Causes Of Cancermentioning

confidence: 93%

The NP9 protein encoded by the human endogenous retrovirus HERV‐K(HML‐2) negatively regulates gene activation of the Epstein‐Barr virus nuclear antigen 2 (EBNA2)

Gross

Barth

Pfuhl

et al. 2011

Intl Journal of Cancer

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Epstein-Barr virus (EBV) is a human tumour virus that efficiently growth-transforms primary human B-lymphocytes in vitro. The viral nuclear antigen 2 (EBNA2) is essential for immortalisation of B-cells and stimulates viral and cellular gene expression through interaction with DNA-bound transcription factors. Like its cellular homologue Notch, it associates with the DNA-bound repressor RBPJj (CSL/CBF1) thereby converting RBPJj into the active state. For instance, both EBNA2 and Notch activate the cellular HES1 promoter. In EBV-transformed lymphocytes, the RNA of the NP9 protein encoded by human endogenous retrovirus HERV-K(HML-2) Type 1 is strongly up-regulated. The NP9 protein is detectable both in EBV-positive Raji cells, a Burkitt's lymphoma cell line, and in IB4, an EBV-transformed human lymphoblastoid cell line. NP9 binds to LNX that forms a complex with the Notch regulator Numb. Therefore, the function of NP9 vis-à-vis Notch and EBNA2 was analysed. Here, we show that NP9 binds to EBNA2 and negatively affects the EBNA2-mediated activation of the viral C-and LMP2A promoters. In contrast, NP9 did neither interfere in the activation of the HES1 promoter by Notch nor the induction of the viral LMP1 promoter by EBNA2. In an electrophoretic mobility shift analysis, NP9 reduced the binding of EBNA2 to DNA-bound RBPJj by about 50%. The down-regulation of EBNA2-activity by NP9 might represent a cellular defence mechanism against viral infection or could, alternatively, represent an adaptation of the virus to prevent excessive viral protein production that might otherwise be harmful for the infected cell.

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TheLMP1 gene isolated from Russian nasopharyngeal carcinoma has no 30-bp deletion

Cited by 36 publications

References 17 publications

Interaction of Epstein-Barr Virus Latent Membrane Protein 1 with SCFHOS/β-TrCP E3 Ubiquitin Ligase Regulates Extent of NF-κB Activation

Interaction of Epstein-Barr Virus Latent Membrane Protein 1 with SCFHOS/β-TrCP E3 Ubiquitin Ligase Regulates Extent of NF-κB Activation

Amino acid changes in functional domains of latent membrane protein 1 of Epstein–Barr virus in nasopharyngeal carcinoma of southern China and Taiwan: prevalence of an HLA A2-restricted ‘epitope-loss variant’

The NP9 protein encoded by the human endogenous retrovirus HERV‐K(HML‐2) negatively regulates gene activation of the Epstein‐Barr virus nuclear antigen 2 (EBNA2)

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