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Host and virus determinants of picornavirus pathogenesis and tropism

Key Points

  • Picornaviruses have caused (poliovirus), and continue to cause (coxsackievirus, rhinovirus, hepatitis A virus, foot-and-mouth-disease virus), substantial clinical and economic hardship.

  • Attempts to eradicate poliovirus have been impressive but, so far, unsuccessful. We discuss the wisdom of abandoning routine poliovirus vaccination if global eradication is achieved.

  • Although the viruses are often highly cytolytic, there is no doubt that some of them can establish chronic infection in vivo, and emerging evidence suggests they might, in some cases, establish a latent infection. The possible mechanisms are discussed, focusing on interactions between the virus and the cell cycle.

  • We review the ability of several picornaviruses to effectively thwart the host's capacity to mount strong CD8+ T-cell responses.

  • Some studies have implicated picornaviruses in autoimmune disease. We evaluate the evidence and present alternative hypotheses.

  • Novel treatments for picornaviral infections are discussed, together with their possible use as in vivo gene-delivery systems.

Abstract

The family Picornaviridae contains some notable members, including rhinovirus, which infects humans more frequently than any other virus; poliovirus, which has paralysed or killed millions over the years; and foot-and-mouth-disease virus, which led to the creation of dedicated institutes throughout the world. Despite their profound impact on human and animal health, the factors that regulate pathogenesis and tissue tropism are poorly understood. In this article, we review the clinical and economic challenges that these agents pose, summarize current knowledge of host–pathogen interactions and highlight a few of the many outstanding questions that remain to be answered.

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Figure 1: Summary of the picornavirus life cycle.
Figure 2: Schematic of the picornavirus genome, the polyprotein products and their main functions.
Figure 3: Type B coxsackievirus 3 (CVB3) targets neuronal progenitor cells in proliferating regions of the central nervous system.

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Acknowledgements

We are grateful to A. Lord for excellent secretarial support. This work was supported by a National Institutes of Health (NIH) award, NIH grants and a National Multiple Sclerosis Society advanced postdoctoral fellowship award. This is manuscript number 17208-NP from the Scripps Research Institute.

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DATABASES

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Hepatitis A virus

Poliovirus

TMEV

type A coxsackievirus

type B coxsackievirus

Infectious Disease Information

Influenza

Poliomyelitis

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CAR

CD155

CD55

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Whitton, J., Cornell, C. & Feuer, R. Host and virus determinants of picornavirus pathogenesis and tropism. Nat Rev Microbiol 3, 765–776 (2005). https://doi.org/10.1038/nrmicro1284

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