The aim of the proposed research is to contribute to a more detailed molecular description of the host antibody response to poliovirus virions. It is proposed that a combination of molecular biologic and immunologic approaches be used to determine A) the immunogenic sites on the poliovirus type 1 virion, specifically the neutralization determinants, B) the viral antigenic determinants recognized by the antivirion antibody response of susceptible and nonsusceptible hosts. To achieve these goals, monoclonal antibodies of predetermined linear antigenic specificity and monoclonal antibodies recognizing virion determinants will be used in conjunction with a recombinant DNA expression library expressing the different epitopes of the virus: 1) To identify the antigenic determinants present on the virion surface to which neutralizing antibodies bind, resulting in loss of infectivity; to isolate mutations in the antigenic determinants which result in loss of epitope recognition by the antibodies and in generation of neutralization resistant viruses and 2) To characterize the spectrum of poliovirus epitopes recognized by antibodies found in the sera from poliovirus-immunized mice and rats and from poliomyelitis patients. The host immune response to the virion is particularly important for a thorough understanding of poliovirus disease pathogenesis. The health relatedness of this proposal derives from its contribution to the understanding of molecular mechanism of viral pathogenesis and to the basis of host protection by poliovirus vaccines.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Virology Study Section (VR)
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Massachusetts Institute of Technology
Schools of Arts and Sciences
United States
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Lin, Jun; Cheng, Naiqian; Chow, Marie et al. (2011) An externalized polypeptide partitions between two distinct sites on genome-released poliovirus particles. J Virol 85:9974-83
Wahid, Rahnuma; Cannon, Martin J; Chow, Marie (2005) Dendritic cells and macrophages are productively infected by poliovirus. J Virol 79:401-9
Wahid, Rahnuma; Cannon, Martin J; Chow, Marie (2005) Virus-specific CD4+ and CD8+ cytotoxic T-cell responses and long-term T-cell memory in individuals vaccinated against polio. J Virol 79:5988-95
Huang, Y; Hogle, J M; Chow, M (2000) Is the 135S poliovirus particle an intermediate during cell entry? J Virol 74:8757-61
Kaufman, M R; Jia, J; Zeng, L et al. (2000) Pseudomonas aeruginosa mediated apoptosis requires the ADP-ribosylating activity of exoS. Microbiology 146 ( Pt 10):2531-41
Tsang, S K; Danthi, P; Chow, M et al. (2000) Stabilization of poliovirus by capsid-binding antiviral drugs is due to entropic effects. J Mol Biol 296:335-40
Vance, L M; Moscufo, N; Chow, M et al. (1997) Poliovirus 2C region functions during encapsidation of viral RNA. J Virol 71:8759-65
Tosteson, M T; Chow, M (1997) Characterization of the ion channels formed by poliovirus in planar lipid membranes. J Virol 71:507-11
Li, Q; Yafal, A G; Lee, Y M et al. (1994) Poliovirus neutralization by antibodies to internal epitopes of VP4 and VP1 results from reversible exposure of these sequences at physiological temperature. J Virol 68:3965-70
Filman, D J; Syed, R; Chow, M et al. (1989) Structural factors that control conformational transitions and serotype specificity in type 3 poliovirus. EMBO J 8:1567-79

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