title: The copy number of Epstein-Barr virus latent genome correlates with the oncogenicity by the activation level of LMP1 and NF-κB.
abstract: A tumor model that Epstein-Barr virus (EBV) latent infection facilitated the tumorigenicity was previously established using the Maxi-EBV system. In the present approach, EBV-lost cell clones demonstrated significantly decreased tumorigenesis. On the other hand, the LMP1 gene in Maxi-EBV genome was replaced by that of nasopharyngeal carcinoma origin. The resultant cell line, 293-1/NL showed much lower malignancy than the original 293-EBV. The result was opposite to our expectation. The change of 293 sublineage cells for EBV harboring also got similar result. To seek the underlying reason, the copy number of EBV genome in all the cell lines was detected. The result indicated that 293-EBV contained about 4.5-fold higher EBV copies than 293-1/NL did. Parallel EBV genomes led to relatively stable copies in different 293 sublineages, suggesting the viral genome structure is a factor for the sustainability of EBV's copy number. Moreover, the LMP1 transcription in high copy-containing cells showed abnormally high level. Furthermore, the main LMP1-driven pathway, transcription factor NF-κB, was highly activated in high-copy cells. Here we first manifest by experimental model that the copy number of EBV latent genome correlates with the viral pathogenesis, which depends on the activation level of LMP1 and NF-κB. Overall, both the presence and amount of EBV genome are crucial for the viral oncogenicity.
authors.affiliation: Central Laboratory, Hunan Provincial Tumor Hospital, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China.|Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
authors.forename: Lielian
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.|Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Yu
authors.affiliation: Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.|Current address: Cancer Research Institute, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Yunlian
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Biological Sciences, Alabama State University, Montgomery, AL 36101, USA.
authors.forename: Hongzhuan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Central Laboratory, Hunan Provincial Tumor Hospital, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China.|Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Du
authors.affiliation: Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.|Current address: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: Central Laboratory, Hunan Provincial Tumor Hospital, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China.|Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: Central Laboratory, Hunan Provincial Tumor Hospital, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, China.|Cancer Research Institute, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D018628:Gene Dosage; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral / Q000235:genetics; D057809:HEK293 Cells; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017735:Virus Latency / Q000235:genetics
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins
keywords: Epstein-Barr virus; copy number; latent genome; latent membrane protein 1; oncogenicity