3CD Cleavage of the Poliovirus P1 Precursor: A Model for Complex Proteinase/Substrate Interactions

  • Wade S. Blair
  • Xiaoyu Li
  • Bert L. Semler
Part of the NATO ASI Series book series (NSSA, volume 240)

Abstract

Eukaryotic viruses have evolved numerous strategies of replication that allow the propagation of their nucleic acid genomes in a potentially hostile host environment. Such strategies often include the limitation of genomic RNA or DNA sequences to only those essential, the production of multiple gene products from a single viral mRNA species, the use of host-cellular replication and translation machinery, and the selective inhibition of host-cell gene expression. Storage of viral genetic information in the form of ribonucleic acid is an additional replication strategy employed by a subgroup of eukaryotic viruses (RNA viruses). Most RNA viruses (excluding orthomyxoviruses and retroviruses) have eliminated the need for a nuclear phase in their viral life cycles, thus facilitating viral gene expression. An instructive example of a well-studied RNA virus which incorporates all of the above mentioned strategies to orchestrate a productive and efficient replication cycle is poliovirus, a member of the family Picornaviridae. Poliovirus is a small, positive-sense RNA virus that encodes at least 14 distinct viral gene products within a monocistronic genome of 7.5 kb (Rueckert, 1985; Lawson and Semler, 1990). This is achieved by translation of the viral mRNA into a single polyprotein that is subsequently cleaved into mature structural and nonstructural viral proteins by viral proteinases 2A and 3C. Proteinase 2A specifically recognizes a tyrosine-glycine (Y-G) amino acid pair and completes the initial cleavage on the polyprotein at the P1/P2 junction (Toyoda et al., 1986). The remainder of the important cleavages within the poliovirus P2 and P3 regions of the polyprotein is mediated by proteinase 3C, which exclusively recognizes glutamine-glycine (Q-G) amino acid pairs (Semler et al., 1981; Emini et al., 1982; Hanecak et al., 1982; Larsen et al., 1982). Cleavage of the P1 precursor requires polymerase sequences (3D) as well as 3C sequences in the form of proteinase 3CD (Jore et al. 1988; Ypma-Wong et al., 1988a). The poliovirus genomic RNA is also characterized by a large untranslated region (∼740 nt) located at the 5′ end (5′ UTR). The 5′ UTR facilitates the translation of viral mRNA by host-cell translation machinery via a novel cap-independent mechanism of translation initiation (Pelletier et al., 1988; Trono et al., 1988). The use of a cap-independent translation initiation mechanism allows for the selective inhibition of host-cell cap-dependent translation of eukaryotic mRNAs, an event mediated by proteinase 2A (Etchison et al., 1982; Sun and Baltimore, 1989).

Keywords

Glycine Serine Proline Polypeptide Arginine 

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Wade S. Blair
    • 1
  • Xiaoyu Li
    • 1
  • Bert L. Semler
    • 1
  1. 1.Department of Microbiology and Molecular GeneticsUniversity of California IrvineUSA

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