Three areas of research on murine leukemia viruses (retroviruses) involving their 1) processing of viral RNAs, 2) regulation of provirus expression, and 3) oncogenicity are included here. Analysis of 38S viral RNAs by the S1 heteroduplex mapping technique will be carried out to determine whether different 38S RNAs exist which differ in their splice patterns. Further studies of structural and functional differences between 38S genomic and messenger RNAs will involve the study of a unique replication-defective Moloney murine leukemia virus (M-MLV) cell clone, NX-3. Studies on the transcriptional regulation of M-MLV proviruses in NRK-4 cells will include the analysis of viral DNA and RNA in cells transfected with DNA from molecular clones of these proviruses. These studies will also examine how the chromosomal conformation of the cellular DNA sites of integration is related to the DNAse I sensitivity of the provirus after integration. Finally, the study of leukemogenesis in the AKR mouse will include the analysis of MLV provirus integration sites and mRNA expression in thymic lymphomas by agarose gel electrophoresis, transfer to nitrocellulose filters and hybridization to viral specific probes. These studies will test different hypotheses involving the role of MLVs in the development of murine lymphocytic leukemia.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA044166-01
Application #
3186750
Study Section
Experimental Virology Study Section (EVR)
Project Start
1986-05-01
Project End
1986-12-31
Budget Start
1986-05-01
Budget End
1986-12-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Yoshimura, Fayth K; Luo, Xixia; Zhao, Xiaoqing et al. (2008) Up-regulation of a cellular protein at the translational level by a retrovirus. Proc Natl Acad Sci U S A 105:5543-8
Zhao, Xiaoqing; Yoshimura, Fayth K (2008) Expression of murine leukemia virus envelope protein is sufficient for the induction of apoptosis. J Virol 82:2586-9
Yoshimura, Fayth K; Luo, Xixia (2007) Induction of endoplasmic reticulum stress in thymic lymphocytes by the envelope precursor polyprotein of a murine leukemia virus during the preleukemic period. J Virol 81:4374-7
Nanua, Suparna; Yoshimura, Fayth K (2004) Mink epithelial cell killing by pathogenic murine leukemia viruses involves endoplasmic reticulum stress. J Virol 78:12071-4
Nanua, Suparna; Yoshimura, Fayth K (2004) Differential cell killing by lymphomagenic murine leukemia viruses occurs independently of p53 activation and mitochondrial damage. J Virol 78:5088-96
Yoshimura, F K; Wang, T (2001) Role of the LTR region between the enhancer and promoter in mink cell focus-forming murine leukemia virus pathogenesis. Virology 283:121-31
Yoshimura, F K; Wang, T; Nanua, S (2001) Mink cell focus-forming murine leukemia virus killing of mink cells involves apoptosis and superinfection. J Virol 75:6007-15
Yoshimura, F K; Wang, T; Yu, F et al. (2000) Mink cell focus-forming murine leukemia virus infection induces apoptosis of thymic lymphocytes. J Virol 74:8119-26
Yoshimura, F K; Wang, T; Cankovic, M (1999) Sequences between the enhancer and promoter in the long terminal repeat affect murine leukemia virus pathogenicity and replication in the thymus. J Virol 73:4890-8
Chen, H; Yoshimura, F K (1998) Spacing between the enhancer and promoter of the long terminal repeat of a murine leukaemia retrovirus is required for transcriptional activation in T cells. J Gen Virol 79 ( Pt 5):1101-4

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