Abstract

The overall aim of this proposal is to further develop our model for B cell activation and proliferation that employs in vitro infection by Epstein-Barr virus. These studies will provide a better understanding of this mechanism of normal and neoplastic B cell growth in vitro and in vivo and on the mechanisms by which EBV sustains a latent infection. The proposal focuses on three membrane proteins whose expression is closely associated with the proliferation of EBV infected B cells. 1) BLAST-1 - a panel of monoclonal antibodies will be raised to BLAST-1 and used to analyze the role of this molecule in proliferation and cell interaction. 2) CD23/BLAST-2 - the end shed form of CD23/BLAST-2 (25 kd chain) is associated with a 12 kd chain of unknown origin. We will analyze the role of this chain in the autocrine growth of B lymphoblasts that is driven by S-BLAST-2. Specific antibody reagents and a cDNA clone will be derived for this purpose using the purified 12 kd protein. 3) p63/LMP - the sites of phosphorylation and specific cleavage of the pp29 subfragment will be identified by purification and specific chemical cleavage and sequencing of pp29. This will then allow the specific mutation of these sites in order to study their role in the function of p63/LMP.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA031893-09
Application #
3482240
Study Section
Virology Study Section (VR)
Project Start
1981-07-01
Project End
1993-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111

  Publications

Monk, J Paul; Halabi, Susan; Picus, Joel et al. (2012) Efficacy of peripheral androgen blockade in prostate cancer patients with biochemical failure after definitive local therapy: results of Cancer and Leukemia Group B (CALGB) 9782. Cancer 118:4139-47
Ianelli, C J; DeLellis, R; Thorley-Lawson, D A (1998) CD48 binds to heparan sulfate on the surface of epithelial cells. J Biol Chem 273:23367-75
Nicholson, L J; Hopwood, P; Johannessen, I et al. (1997) Epstein-Barr virus latent membrane protein does not inhibit differentiation and induces tumorigenicity of human epithelial cells. Oncogene 15:275-83
Brodeur, S R; Cheng, G; Baltimore, D et al. (1997) Localization of the major NF-kappaB-activating site and the sole TRAF3 binding site of LMP-1 defines two distinct signaling motifs. J Biol Chem 272:19777-84
Miyashita, E M; Yang, B; Babcock, G J et al. (1997) Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell. J Virol 71:4882-91
Ianelli, C J; Edson, C M; Thorley-Lawson, D A (1997) A ligand for human CD48 on epithelial cells. J Immunol 159:3910-20
Sutkowski, N; Palkama, T; Ciurli, C et al. (1996) An Epstein-Barr virus-associated superantigen. J Exp Med 184:971-80
Decker, L L; Klaman, L D; Thorley-Lawson, D A (1996) Detection of the latent form of Epstein-Barr virus DNA in the peripheral blood of healthy individuals. J Virol 70:3286-9
Khan, G; Miyashita, E M; Yang, B et al. (1996) Is EBV persistence in vivo a model for B cell homeostasis? Immunity 5:173-9
Decker, L L; Shankar, P; Khan, G et al. (1996) The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients. J Exp Med 184:283-8

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