The purpose of this proposal is to further investigate the structural proteins of polyomavirus and to determine their respective role(s) in the virion structure, virion assembly, viral infection and cell transformation, the unique aspects of our proposed investigation include: I. The structural organization of polyoma virions will be studied to determine the virion location of BP1 species, VP2 and VP3, and the identification of inter and intra-molecular disulfide linkages in the virion structure. II. The presence of post-translational modifications and the domains of protein modifications residing in the structural proteins will be identified. Important reactive sites in the structural proteins will be identified by using synthetic peptides, site directed oligonucleotide mutagenesis and an expanded monoclonal antibody bank. III. To identify the cellular (cytoplasmic or nuclear) location for post- translational modifications of polyoma polypeptides and to determine the mechanism(s) involved in the transport of newly synthesized virion polypeptides into the nucleus. Selected enzymes involved in phosphorylation and hydroxylation of the structural proteins will be analyzed during infection. IV. The polyomavirus-mouse cell receptor will be isolated and biochemically characterized as to protein, glycosylation and lipid content. Various permissive and non-permissive cells to polyoma infection will be analyzed for the presence of specific polyomavirus-mouse cell receptor. V. The virion-mouse cell receptor interaction will be investigated to determine the effect on virion structure as to conformational changes due to adsorption and the physiological role(s) triggered at the cellular level involving cellular kinase activity. Studies will also include the identification of possible normal cell polypeptide growth factor(s) which share the polyoma-mouse cell receptor.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA007139-30
Application #
2084558
Study Section
Virology Study Section (VR)
Project Start
1979-05-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1996-04-30
Support Year
30
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Kansas State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Manhattan
State
KS
Country
United States
Zip Code
66506