Murine leukemia viruses (MuLVs) are potent inducers of hematopoietic tumors in mice. Transcriptional regulatory sequences within the long terminal repeats (LTRs) of these viruses control the expression of the viral genomes and play crucial roles in the process of tumorigenesis by these viruses. They determine the type of tumor that specific MuLVs cause, they influence the ability of the viruses to infect the target cells for disease, and they play a role in the tumorigenic activation of cellular genes following adjacent insertion of the viral genomes. Experiments are proposed here to compare the transcriptional capacity of different MuLVs on templates that are integrated at various sites in the mouse genome. These experiments will use cells from the lineages in which these viruses cause tumors. A second line of experiments is proposed to identify the cellular genes that are activated by these viruses in tumors and to begin to test how these genes participate in tumorigenesis. High-throughput technology is now available that allows such genetic screens to be performed far more rapidly than in the past. This approach will be applied to two separate MuLV tumor systems. The genes that are identified in these screens are expected to provide insight about important and perhaps unanticipated molecular mechanisms that contribute to the generation of leukemias and lymphomas.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA044822-15
Application #
6621215
Study Section
Virology Study Section (VR)
Program Officer
Cole, John S
Project Start
1987-05-01
Project End
2006-11-30
Budget Start
2002-12-04
Budget End
2003-11-30
Support Year
15
Fiscal Year
2003
Total Cost
$371,575
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
071036636
City
Bronx
State
NY
Country
United States
Zip Code
10461
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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