Epstein-Barr virus latent infection membrane protein alters the human B-lymphocyte phenotype: deletion of the amino terminus abolishes activity.
A latent infection membrane protein (LMP) encoded by the Epstein-Barr virus (EBV) genome in latently infected, growth-transformed lymphocytes alters the phenotype of a human EBV-negative B-lymphoma cell line (Louckes) when introduced by gene transfer. These LMP-expressing cells exhibit increased homotypic adhesion due to increased expression of the adhesion molecules LFA-1 and ICAM-1. Increased homotypic adhesion could foster B-cell growth by facilitating autocrine growth factor effects. LFA-3 expression is also induced. The induction of LFA-3 and ICAM-1 results in increased heterotypic adhesion to T lymphocytes. This could result in more effective T-cell immune surveillance. Since LMP is expressed in EBV-transformed lymphocytes and has been demonstrated to transform rodent fibroblasts in vitro, a wide range of possible effects on B-lymphoma cell growth were assayed. In the Louckes B-lymphoma cell line, EBV LMP causes increased cell size, acid production, plasma membrane ruffling, and villous projections. Although cell proliferation rate was not greatly affected, the steady-state intracellular free calcium level, transforming growth factor beta responsiveness, and expression of the lymphocyte activation markers (CD23 and transferrin receptor) were increased. Thus, LMP appears to be a mediator of EBV effects on B-cell transformation. In transfected lymphoma cells, LMP localizes to patches at the cell periphery and associates with the cytoskeleton as it does in EBV-transformed B lymphocytes or in rodent fibroblasts. A partially deleted form of LMP (D1LMP) does not aggregate in patches or associate with the cytoskeleton and had little effect on B-cell growth. Thus, cytoskeletal association may be integral to LMP activity.
Wang
D
D
Department of Medicine, Harvard University Medical School, Boston, Massachusetts 02115.
Liebowitz
D
D
Wang
F
F
Gregory
C
C
Rickinson
A
A
Larson
R
R
Springer
T
T
Kieff
E
E
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral / Q000096:biosynthesis / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism / Q000382:microbiology*; D002448:Cell Adhesion; D002449:Cell Aggregation; D002461:Cell Line, Transformed; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008668:Metallothionein / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011990:Receptors, Transferrin / Q000096:biosynthesis; D014162:Transfection; D015291:Transforming Growth Factors / Q000502:physiology; D014763:Viral Matrix Proteins
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011990:Receptors, Transferrin; D014763:Viral Matrix Proteins; D015291:Transforming Growth Factors; D008668:Metallothionein