Elsevier

Virus Research

Volume 111, Issue 2, August 2005, Pages 175-193
Virus Research

Review
Poliovirus and poliomyelitis: A tale of guts, brains, and an accidental event

https://doi.org/10.1016/j.virusres.2005.04.008Get rights and content

Abstract

Nearly 100 years after its discovery poliovirus remains one of most thoroughly studied and best understood virus models for the molecular virologist. While poliovirus has been of vital importance for our insight into picornavirus biology at the cellular and biochemical level, it is ironic to note that, due to the early success in defeating poliomyelitis in the developed world through vaccination, many of the basic aspects of poliovirus pathogenesis remain poorly understood. This is chiefly due to the lack of an adequate and affordable animal model, save of old world monkeys. Fundamental questions, such as the identity of the target cells during the enteric phase of infection, or mechanisms of systemic spread are still unanswered. This review will attempt to summarize our current knowledge of the molecular biology of poliovirus, its pathogenesis, as well as recent advances in the areas of cell and tissue tropism and mechanisms of central nervous system invasion.

Section snippets

General introduction

Poliovirus (PV), the causative agent of poliomyelitis (Landsteiner and Popper, 1909), is a member of the genus Enterovirus of the Picornaviridae, a large family of small (Lat. pico), non-enveloped (+) stranded RNA viruses. Other members of the picornavirus family include the genera of Rhinovirus (common cold virus) with over 100 serotypes, Hepatovirus including human hepatitis A virus, and two prominent animal virus genera Cardiovirus (encephalomyocarditis virus, Theiler's murine

Genome organization

The poliovirus genome consists of a single (+) sense RNA molecule of about 7440 nucleotides (Fig. 1). A relatively long 5′ NTR of 742 nt is followed by a single open reading frame coding for a polyprotein of 2209 amino acids and a 3′ NTR of 70 nt (Dorner et al., 1982, Kitamura et al., 1981, Racaniello and Baltimore, 1981b). The first 88 nucleotides at the 5′ end of the genome form a clover leaf like secondary structure (Andino et al., 1990, Rivera et al., 1988), which has been implicated in the

Cell entry

Poliovirus attachment to the host cell surface is mediated by binding to the N-terminal V-type immunoglobulin like domain of its cognate receptor, CD155 (Koike et al., 1991a, Mendelsohn et al., 1989, Selinka et al., 1991; the physiological function of CD155 will be discussed below). The interaction of poliovirus with its receptor has been thoroughly studied. Mutational and genetic analysis indicated early on that CD155 inserts itself into a surface depression known as the “canyon” which

The poliovirus receptor CD155

Whereas the study of poliovirus biology flourished at the molecular level, progress in the areas of pathogenesis and the interactions of the virus with its human host all but arrested at a 1950s level. Humans and non-human primates are the only natural hosts for poliovirus. Primate research is very expensive and cases of human poliomyelitis due to circulating wild type viruses dwindled due to the great success of the existing poliovirus vaccines. Mice or any other affordable experimental

Poliovirus pathogenesis

Typically, the most frequent manifestation of PV infection in humans is the replication in the gastrointestinal tract and subsequent shedding of the virus in feces (Melnick, 1996, Sabin, 1956). Poliovirus initially gains entry through oral route and infects susceptible cells of the mouth, nose, and throat (Bodian and Horstmann, 1965, Melnick, 1996). The incubation period ranges from 7 to 14 days but may vary from 2 to 35 days. Although the precise sites and cell types involved in the primary

The global effort to eradicate poliovirus

The distinct modes of administration (oral) and mechanisms of eliciting a protective immune response (mucosal and humoral immunity) made the three Sabin isolates the overwhelming favorites for mass vaccinations. Vaccination with the killed vaccine was abandoned except for very few small countries in Europe. Indeed, trivalent OPV proved to be the vaccine of choice for initiating a campaign for poliovirus eradication. Accordingly, the World Health Organization adopted an action plan in May 1988

Concluding remarks

Although a wealth of information has been gathered over a century of intense research on poliovirus a detailed model of the progression of events from infection to poliomyelitis is still missing. The most pressing question remains to be answered: what cells in the GI tract support abundant poliovirus replication and how does the virus enter general circulation? But even the steps following viremia are mostly obscure although the mechanism of retrograde axonal transport is gaining rapidly

Acknowledgements

The authors wish to thank their colleagues for numerous discussions and suggestions. The work from the authors’ laboratory described here was supported in part by grants from National Institute of Health AI-39485, AI-15122, and AI-32100.

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