Determinants of Poliovirus Pathogenesis

Abstract

This chapter provides a brief synopsis of the natural history of paralytic poliomyelitis, and gives an overview of the status of research concerning the molecular determinants of the pathogenesis of paralytic poliomyelitis. Determinants of the pathogenesis of poliomyelitis are either of viral origin, e.g., non-coding viral sequences, structural or nonstructural viral gene products, or of host origin, e.g., distribution of the cellular receptor and host cell factors required for viral replication. To provide a rational account of the relative contributions of a multitude of factors toward a complex phenomenon, the chapter is subdivided into sections dealing with the main parameters of poliovirus neurological disease. Tropism, neurovirulence, and conditions of the host are discussed separately. The chapter discusses experimental evidence for the genetic basis of neurovirulence in the 5∇ non-translated region (5' NTR) and the coding regions for the structural and nonstructural proteins of poliovirus. Extraneural determinants of neuropathogenicity, such as invasion of or spread within the CNS, combine with intraneural factors, such as IRES-mediated cell type specificity or the efficiency of genome replication. Excellent studies in nonhuman primates in the prevaccine era and recent progress through the advent of genetic engineering and transgenic animal models for human disease have afforded us detailed insight into the pathogenic mechanism of paralytic poliomyelitis.