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Picornavirus Protein Processing—Enzymes, Substrates, and Genetic Regulation

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Picornaviruses

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 161))

Abstract

The sequence of events leading to the successful completion of a Picornavirus infection of susceptible cells is ultimately controlled by proteolytic processing. As a consequence of encoding their viral-specific polypeptides within a single, open reading frame, picornaviruses must depend upon the intramolecular and intermolecular interactions of viral proteinases and their cognate substrates. This chapter will first provide an overview of how the biosynthetic activities that occur during a picornavirus life cycle are regulated by protein processing activities and signals encoded in the viral genome. An examination of the nature of picornavirus proteinases and their polyprotein substrates will be presented in order to underscore the unifying principles of proteolytic cleavage and to point out the peculiar differences in processing strategies among the different picornaviruses. The application of recombinant DNA methodologies, particularly site-specific mutagenesis, to the study of structure/function relationships of picornavirus cleavage activities will then be discussed. This discussion will also focus on the molecular genetics of viable virus mutants with engineered processing lesions and on in vitro expression of altered cleavage phenotypes. Finally, the biochemical implications of the observed picornavirus processing activities will be addressed. In particular, primary sequence versus conformational determinants of protein processing will be analyzed, as well as the importance of cis versus trans cleavage.

Work described from the authors’ laboratory was supported by a grant from the US Public Health Service (AI22693). M.A.L. is a predoctoral trainee of the US Public Health Service (CA09054). B.L.S. is the recipient of a Research Career Development Award (AI00721) from the National Institutes of Health.

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Lawson, M.A., Semler, B.L. (1990). Picornavirus Protein Processing—Enzymes, Substrates, and Genetic Regulation. In: Racaniello, V.R. (eds) Picornaviruses. Current Topics in Microbiology and Immunology, vol 161. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75602-3_3

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