Abstract

The primary goal of this research is to understand the molecular events that underlie the process of leukemogenesis by C-type murine retroviruses (MuLVs). Specifically, the T-cell lymphomagenic virus SL3-3 (SL3) will be studied with respect to the enhancer elements within the Long Terminal Repeats.
Three specific aims are proposed. 1) To define the interactions among the cellular transcription factors in T-lymphocytes that can activate the SL3 enhancer. Three factors will be focused on: CBF, c-Myb, and Ets-1. 2) Key aspects of transcriptional regulation for lymphomagenesis by SL3 will be studied. Critical elements in the SL3 enhancer will be further defined. Mutations within the enhancers will be examined to see if the affect viral replication in cultured T cells and in the lymphoid organs in mice. 3) The ability of these enhancers to activate the promoters of cellular proto-oncogenes in T-cell lymphomas will be analyzed. Specifically, the activation of c-myc and pim-1 will be studied. Additional studies will aim at identifying alternative proto-oncogenes which may be activated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA044822-11
Application #
2837624
Study Section
Virology Study Section (VR)
Program Officer
Cole, John S
Project Start
1987-05-01
Project End
2001-11-30
Budget Start
1998-12-03
Budget End
1999-11-30
Support Year
11
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Heslin, David J; Murcia, Pablo; Arnaud, Frederick et al. (2009) A single amino acid substitution in a segment of the CA protein within Gag that has similarity to human immunodeficiency virus type 1 blocks infectivity of a human endogenous retrovirus K provirus in the human genome. J Virol 83:1105-14
Kim, Rachel; Trubetskoy, Alla; Suzuki, Takeshi et al. (2003) Genome-based identification of cancer genes by proviral tagging in mouse retrovirus-induced T-cell lymphomas. J Virol 77:2056-62
Lenz, J; Su, M; Mizrachi, Y et al. (2001) V3 variation in HIV-seropositive patients receiving a V3- targeted vaccine. AIDS 15:577-81
Rulli, K; Lobelle-Rich, P A; Trubetskoy, A et al. (2001) Tissue distribution and timing of appearance of polytropic envelope recombinants during infection with SL3-3 murine leukemia virus or its weakly pathogenic SL3DeltaMyb5 mutant. J Virol 75:522-6
Barbulescu, M; Turner, G; Su, M et al. (2001) A HERV-K provirus in chimpanzees, bonobos and gorillas, but not humans. Curr Biol 11:779-83
Turner, G; Barbulescu, M; Su, M et al. (2001) Insertional polymorphisms of full-length endogenous retroviruses in humans. Curr Biol 11:1531-5
Beaty, R M; Rulli, K; Bost, K L et al. (1999) High levels of IL-4 and IL-10 mRNA and low levels of IL-2, IL-9 and IFN-gamma mRNA in MuLV-induced lymphomas. Virology 261:253-62
Martiney, M J; Rulli, K; Beaty, R et al. (1999) Selection of reversions and suppressors of a mutation in the CBF binding site of a lymphomagenic retrovirus. J Virol 73:7599-606
Rubinstein, A; Mizrachi, Y; Pettoello-Mantovani, M et al. (1999) Immunologic responses of HIV-1-infected study subjects to immunization with a mixture of peptide protein derivative-V3 loop peptide conjugates. J Acquir Immune Defic Syndr 22:467-76
Trubetskoy, A M; Okenquist, S A; Lenz, J (1999) R region sequences in the long terminal repeat of a murine retrovirus specifically increase expression of unspliced RNAs. J Virol 73:3477-83

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