Abstract

The proposed studies are a Renewal Application on """"""""Molecular Genetic Studies of the Human T-Cell Leukemia Viruses"""""""". The human T-cell leukemia viruses, HTLV-I and HTLV-II, are the only known oncogenic retroviruses of man, and are the etiologic agents of specific T-cell malignancies, adult T-cell leukemia, and possibly some forms of a typical hairy-cell leukemia. The processes of HTLV replication and the mechanisms of T-cell transformation are unique among animal retroviruses. Over the past several years, we and other investigators have identified transcriptional activating functions in the HTLV genome, and identified the protein product of the gene encoding these functions. In addition, we have characterized the structure, expression and some functions of these trans-acting functions. The studies proposed in this Application are a direct extension of these previous studies. The specific goals are: 1. To further characterize cis-acting functions of the HTLV LTR responsive to trans-acting viral functions. 2. To further characterize trans-acting viral functions by mutagenesis. 3. To identify and characterize viral functions responsible for T- cell immortalization/transformation. We have established a number of unique reagents and approaches, particularly for HTLV-II, and these will be applied to the proposed studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37CA038597-04
Application #
3482413
Study Section
Virology Study Section (VR)
Project Start
1985-01-01
Project End
1992-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Poon, B; Chen, I S (1998) Identification of a domain within the human T-cell leukemia virus type 2 envelope required for syncytium induction and replication. J Virol 72:1959-66
Stewart, S A; Feuer, G; Jewett, A et al. (1996) HTLV-1 gene expression in adult T-cell leukemia cells elicits an NK cell response in vitro and correlates with cell rejection in SCID mice. Virology 226:167-75
Cockerell, G L; Rovnak, J; Green, P L et al. (1996) A deletion in the proximal untranslated pX region of human T-cell leukemia virus type II decreases viral replication but not infectivity in vivo. Blood 87:1030-5
Li, Q X; Camerini, D; Xie, Y et al. (1996) Syncytium formation by recombinant HTLV-II envelope glycoprotein. Virology 218:279-84
Feuer, G; Fraser, J K; Zack, J A et al. (1996) Human T-cell leukemia virus infection of human hematopoietic progenitor cells: maintenance of virus infection during differentiation in vitro and in vivo. J Virol 70:4038-44
Green, P L; Yip, M T; Xie, Y et al. (1992) Phosphorylation regulates RNA binding by the human T-cell leukemia virus Rex protein. J Virol 66:4325-30
Green, P L; Xie, Y M; Chen, I S (1991) The Rex proteins of human T-cell leukemia virus type II differ by serine phosphorylation. J Virol 65:546-50
Arrigo, S J; Chen, I S (1991) Rev is necessary for translation but not cytoplasmic accumulation of HIV-1 vif, vpr, and env/vpu 2 RNAs. Genes Dev 5:808-19
Yip, M T; Dynan, W S; Green, P L et al. (1991) Human T-cell leukemia virus (HTLV) type II Rex protein binds specifically to RNA sequences of the HTLV long terminal repeat but poorly to the human immunodeficiency virus type 1 Rev-responsive element. J Virol 65:2261-72
Black, A C; Chen, I S; Arrigo, S et al. (1991) Regulation of HTLV-II gene expression by Rex involves positive and negative cis-acting elements in the 5'long terminal repeat. Virology 181:433-44

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