Abstract

Picornaviruses comprise a large group of RNA viruses that cause a multitude of serious illness among humans. Included are meningitis, myocarditis, poliomyelitis, hepatitis, hand-foot-and- mouth disease, and hemorrhagic conjunctivitus. Guanidine has been found to selectively inhibit growth of many picornaviruses at millimolar levels without adversely affecting host cells. Hopefully, this compound will prove to have chemotherapeutic value alone or in combination with other anti-viral compounds. We have recently determined the site of guanidine action with drug resistant mutants of poliovirus and plan to determine the mechanism whereby RNA synthesis of virus is blocked. We will determine 1 what amino acid changes confer guanidine resistance or dependence to virus, 2 whether the guanidine marker is restricted to several domains in the 2C locus, and 3 whether amino acid sequences that confer guanidine resistance are identical among types 1 and 3 polioviruses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023717-02
Application #
3136041
Study Section
Experimental Virology Study Section (EVR)
Project Start
1987-09-30
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Pennsylvania State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802

  Publications

Baltera Jr, R F; Tershak, D R (1992) Role of amino acid residue 187 of poliovirus polypeptide 2C in determining the guanidine trait. Intervirology 33:165-72
Hoyer, J T; Morris, J F; Pierce, S K (1992) The delayed acquisition of antigen-processing distinguishes immature B cells in adults and neonates. Ann N Y Acad Sci 651:72-4
Morris, J F; Hoyer, J T; Pierce, S K (1992) Antigen presentation for T cell interleukin-2 secretion is a late acquisition of neonatal B cells. Eur J Immunol 22:2923-8
Tershak, D R; Allegretto, K D (1991) A replication-defective variant of Sabin 3 poliovirus. Intervirology 32:127-36
Smolenski, L A; Kaumaya, P; Atassi, M Z et al. (1990) Characteristics of peptides which compete for presented antigen-binding sites on antigen-presenting cells. Eur J Immunol 20:953-60
Srinivasan, M; Pierce, S K (1990) Isolation of a functional antigen-Ia complex. Proc Natl Acad Sci U S A 87:919-22
Vanbuskirk, A; Crump, B L; Margoliash, E et al. (1989) A peptide binding protein having a role in antigen presentation is a member of the HSP70 heat shock family. J Exp Med 170:1799-809
Baltera Jr, R F; Tershak, D R (1989) Guanidine-resistant mutants of poliovirus have distinct mutations in peptide 2C. J Virol 63:4441-4
Casten, L A; Pierce, S K (1988) Receptor-mediated B cell antigen processing. Increased antigenicity of a globular protein covalently coupled to antibodies specific for B cell surface structures. J Immunol 140:404-10
Casten, L A; Kaumaya, P; Pierce, S K (1988) Enhanced T cell responses to antigenic peptides targeted to B cell surface Ig, Ia, or class I molecules. J Exp Med 168:171-80

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