Abstract

This application proposes to merge the work presently supported by three separate grants dealing with various aspects of work on polyoma virus. Molecular biological studies of polyoma virus interactions with susceptible cells in culture are being pursued with the particular goal of understanding the roles of the middle T and small T proteins in cell transformation and in productive viral infection. Structure-function studies of middle T using oligonucleotide mutagenesis are proposed, with the aim of elucidating the interaction of this viral protein with cellular protein kinases, and possibly with phospholipid metabolism. With respect to the virus growth cycle, similar approaches are being used to study VP/1 and its phosphorylation sites in order to gain a better understanding of how such modifications of the major capsid protein may be important in assembly of the virus particle. A third area deals with interactions of the virus with the intact host, in particular with the immune system and recognition of the polyoma-specific transplantation antigens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA044343-05
Application #
3479512
Study Section
Special Emphasis Panel (SRC (88))
Project Start
1987-09-01
Project End
1994-08-31
Budget Start
1991-09-20
Budget End
1992-08-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Gilbert, Joanna M; Goldberg, Ilya G; Benjamin, Thomas L (2003) Cell penetration and trafficking of polyomavirus. J Virol 77:2615-22
Velupillai, Palanivel; Carroll, John P; Benjamin, Thomas L (2002) Susceptibility to polyomavirus-induced tumors in inbred mice: role of innate immune responses. J Virol 76:9657-63
Dey, Dilip; Dahl, Jean; Cho, Sayeon et al. (2002) Induction and bypass of p53 during productive infection by polyomavirus. J Virol 76:9526-32
Li, D; Dower, K; Ma, Y et al. (2001) A tumor host range selection procedure identifies p150(sal2) as a target of polyoma virus large T antigen. Proc Natl Acad Sci U S A 98:14619-24
Cho, S; Tian, Y; Benjamin, T L (2001) Binding of p300/CBP co-activators by polyoma large T antigen. J Biol Chem 276:33533-9
Dey, D C; Bronson, R P; Dahl, J et al. (2000) Accelerated development of polyoma tumors and embryonic lethality: different effects of p53 loss on related mouse backgrounds. Cell Growth Differ 11:231-7
Gilbert, J M; Benjamin, T L (2000) Early steps of polyomavirus entry into cells. J Virol 74:8582-8
Bauer, P H; Cui, C; Liu, W R et al. (1999) Discrimination between sialic acid-containing receptors and pseudoreceptors regulates polyomavirus spread in the mouse. J Virol 73:5826-32
Carroll, J P; Fung, J S; Bronson, R T et al. (1999) Radiation-resistant and radiation-sensitive forms of host resistance to polyomavirus. J Virol 73:1213-8
Velupillai, P; Yoshizawa, I; Dey, D C et al. (1999) Wild-derived inbred mice have a novel basis of susceptibility to polyomavirus-induced tumors. J Virol 73:10079-85

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