Human T cell leukemia (HTLV) is a retroviral family associated with a number of human diseases, including adult T cell leukemia/lymphoma, hairy cell leukemia, and acquired immune deficiency syndrome (AIDS). The genome of HTLV possesses a unique region at its 3' end designated pX. The pX region consists of four open reading frames. It is unknown whether this region is expressed during HTLV infection or transformation. We wish to investigate the structure, origin, expression and function of the pX region. The structure of the pX region will be determined by restriction endonuclease mapping, hybridization studies and primary DNA sequence analysis of cloned HTLV isolates. The origin of the pX region will be investigated by Southern blot analysis of vertebrate DNAs under relaxed conditions of hybridization. The expression of the pX region will be studied by Northern blot analysis of HTLV-associated tumors. We plan to use in vitro translation of hybrid-selected RNAs, expression in eukaryotic and bacterial systems, and synthetic peptides to study the protein products of this region. Functional analysis of the pX proteins will be done by characterizing the phenotypic effects of pX expression in eukaryotic cells, by observing the effect of pX deletions on HTLV replication and in vitro immortalization ability and by determining whether the presence of the pX region affects the replication and/or pathogenicity of animal leukemia viruses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036974-02
Application #
3174639
Study Section
Experimental Virology Study Section (EVR)
Project Start
1984-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
Poteat, H T; Ramstedt, U; Yoon, S et al. (1996) Cyclic AMP-mediated growth arrest is associated with increased expression of human T cell leukemia virus type I structural and transforming genes. AIDS Res Hum Retroviruses 12:527-33
Ueberla, K; Lu, Y; Chung, E et al. (1993) The NF-kappa B p65 promoter. J Acquir Immune Defic Syndr 6:227-30
Caputo, A; Haseltine, W A (1992) Reexamination of the coding potential of the HTLV-1 pX region. Virology 188:618-27
Grassmann, R; Berchtold, S; Radant, I et al. (1992) Role of human T-cell leukemia virus type 1 X region proteins in immortalization of primary human lymphocytes in culture. J Virol 66:4570-5
Kalland, K H; Langhoff, E; Bos, H J et al. (1991) Rex-dependent nucleolar accumulation of HTLV-I mRNAs. New Biol 3:389-97
Zazopoulos, E; Sodroski, J G; Haseltine, W A (1990) p21rex protein of HTLV-1. J Acquir Immune Defic Syndr 3:1135-9
Poteat, H T; Chen, F Y; Kadison, P et al. (1990) Protein kinase A-dependent binding of a nuclear factor to the 21-base-pair repeat of the human T-cell leukemia virus type I long terminal repeat. J Virol 64:1264-70
Dokhelar, M C; Pickford, H; Sodroski, J et al. (1989) HTLV-I p27rex regulates gag and env protein expression. J Acquir Immune Defic Syndr 2:431-40
Dokhelar, M C; Pickford, H; Sodroski, J et al. (1989) The potential for homeostatic regulation of the X region proteins of the human T cell leukemia virus type I. J Acquir Immune Defic Syndr 2:588-94
Grassmann, R; Dengler, C; Muller-Fleckenstein, I et al. (1989) Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector. Proc Natl Acad Sci U S A 86:3351-5

Showing the most recent 10 out of 20 publications