Abstract

We propose to use the polyoma virus-mouse system to investigate aspects of virus-host interactions leading to induction of tumors. Two areas of general relevance to the biology of cancer will be investigated. The first concerns the apparent inability of polyoma virus to block the actions of p53, raising questions of the role of genomic instability in driving tumor development in this system. This will be approached using molecular cytogenetic techniques to study genomic changes in polyoma-induced mouse tumors, studies in tissue culture to determine how the virus may override or bypass p53, and derivation of transgenic mice expressing regulatable polyoma T (tumor) antigens. The second area concerns the roles of the host genetic background in determining patterns of susceptibility and resistance to tumors. Three mouse strains exhibiting different tumor responses will be studied - 1) susceptibility to tumor induction based on failure to develop tumor immunity, 2) tissue specific resistance to mammary tumors, and 3) propensity of bone tumors to metastasize to the lung. Genetic and physiological approaches will be used in attempts to understand the bases of these host phenotypes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090992-04
Application #
6795869
Study Section
Virology Study Section (VR)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
2001-09-01
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
4
Fiscal Year
2004
Total Cost
$763,109
Indirect Cost

  Institution

Name
Harvard University
Department
Pathology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

You, John; O'Hara, Samantha D; Velupillai, Palanivel et al. (2015) Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus. PLoS Pathog 11:e1005175
Velupillai, Palanivel; Sung, Chang Kyoo; Andrews, Erik et al. (2012) Polymorphisms in toll-like receptor 4 underlie susceptibility to tumor induction by the mouse polyomavirus. J Virol 86:11541-7
Velupillai, Palanivel; Sung, Chang Kyoo; Tian, Yu et al. (2010) Polyoma virus-induced osteosarcomas in inbred strains of mice: host determinants of metastasis. PLoS Pathog 6:e1000733
Sullivan, Christopher S; Sung, Chang K; Pack, Christopher D et al. (2009) Murine Polyomavirus encodes a microRNA that cleaves early RNA transcripts but is not essential for experimental infection. Virology 387:157-67
Whalen, Kerry A; Weber, Georg F; Benjamin, Thomas L et al. (2008) Polyomavirus middle T antigen induces the transcription of osteopontin, a gene important for the migration of transformed cells. J Virol 82:4946-54
Carroll, John; Dey, Dilip; Kreisman, Lori et al. (2007) Receptor-binding and oncogenic properties of polyoma viruses isolated from feral mice. PLoS Pathog 3:e179
Tian, Yu; Kolb, Robert; Hong, Jeong-Ho et al. (2007) TAZ promotes PC2 degradation through a SCFbeta-Trcp E3 ligase complex. Mol Cell Biol 27:6383-95
Dahl, Jean; Chen, H Isaac; George, Michael et al. (2007) Polyomavirus small T antigen controls viral chromatin modifications through effects on kinetics of virus growth and cell cycle progression. J Virol 81:10064-71
Velupillai, Palanivel; Garcea, Robert L; Benjamin, Thomas L (2006) Polyoma virus-like particles elicit polarized cytokine responses in APCs from tumor-susceptible and -resistant mice. J Immunol 176:1148-53
Dahl, Jean; You, John; Benjamin, Thomas L (2005) Induction and utilization of an ATM signaling pathway by polyomavirus. J Virol 79:13007-17

Showing the most recent 10 out of 12 publications