title: LMP1 strain variants: biological and molecular properties.
abstract: The ubiquitous herpesvirus Epstein-Barr virus (EBV) is linked to the development of several malignancies, including nasopharyngeal carcinoma. Latent membrane protein 1 (LMP1) is considered the EBV oncogene as it is necessary for EBV-induced transformation of B lymphocytes and is able to transform Rat-1 fibroblasts. LMP1 can activate a wide array of signaling pathways, including phosphatidylinositol 3-kinase (PI3K)-Akt and NF-kappaB. Six sequence variants of LMP1, termed Alaskan, China 1, China 2, Med+, Med-, and NC, have been identified, and individuals can be infected with multiple variants. The frequencies of detection of these variants differ for various EBV-associated malignancies from different geographic regions. In this study, the biological and signaling properties of the LMP1 variants have been characterized. All of the LMP1 variants transformed Rat-1 fibroblasts, induced increased motility of HFK cells, and induced increased homotypic adhesion of BJAB cells. While all the variants activated the PI3K-Akt signaling pathway to similar extents, the Alaskan, China 1, and Med+ variants had limited binding to the E3 ubiquitin ligase component homologue of Slimb and had slightly enhanced NF-kappaB signaling. These findings indicate that the signature amino acid changes of the LMP1 variants do not hinder or enhance their in vitro transforming potentials or affect their signaling properties.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Mainou
authors.forename: Nancy
authors.initials: N
authors.lastname: Raab-Traub
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000821:virology; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D014644:Genetic Variation; D006461:Hemolysis / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000235:genetics*; D013045:Species Specificity; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D009856:Oncogene Proteins, Viral; D014763:Viral Matrix Proteins; D044767:Ubiquitin-Protein Ligases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt