Abstract

Theiler's virus offers a remarkable example of a pathogen that navigates the various cells of the organism to evade immune responses and establish a persistent infection. Here, we discuss the transition from neuron to myelin and oligodendrocyte infection, a step that is crucial for the persistence of this virus in the central nervous system (CNS). CNS myelin is an extension of the cytoplasmic membrane of oligodendrocytes wrapped numerous times around axons. An oligodendrocyte sends many such extensions and can myelinate up to 50 different axons. Myelinated axon segments are separated by short unmyelinated regions called nodes of Ranvier. Cytoplasm is totally extruded from myelin except in areas where it forms channels that are in continuity with the oligodendrocyte cell body. These channels form the so-called ad-axonal inner loop and the paranodal loops at the level of the nodes of Ranvier. Inner and paranodal loops are in close contact with the axon membrane (Figure 1). (For a review of myelin and node organization, see [1].) Figure 1 Diagrammatic view of CNS myelin.

Highlights

  • central nervous system (CNS) myelin is an extension of the cytoplasmic membrane of oligodendrocytes wrapped numerous times around axons

  • Cytoplasm is totally extruded from myelin except in areas where it forms channels that are in continuity with the oligodendrocyte cell body

  • The virus is no longer in neurons during persistent infection. It is found in white matter, in oligodendrocytes, in the cytoplasmic channels of myelin, and in macrophages

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Summary

Introduction

CNS myelin is an extension of the cytoplasmic membrane of oligodendrocytes wrapped numerous times around axons. Cytoplasm is totally extruded from myelin except in areas where it forms channels that are in continuity with the oligodendrocyte cell body. Theiler’s virus infects neurons and is transported in axons in these mutant mice just as in wildtype mice. We postulated that viruses transported in axons infect the surrounding myelin and spread to oligodendrocyte cell bodies, to macrophages, where infection persists.

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