Implications of Axoplasmic Transport for the Spread of Virus Infections in the Nervous System

Kristensson, Krister

doi:10.1007/978-3-642-85714-0_21

Cited by 18 publications

(9 citation statements)

References 31 publications

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“…Little is known about the exact mechanism by which MHV is transported along nerves . Herpes simplex virus appears to undergo fast axonal transport in both anterograde and retrograde directions, dependent on whether the virus is inoculated intradermally or intramuscularly (22,23) . Similarly, in studies with the type 3 strain of reovirus, Tyler et al .…”

Section: Discussionmentioning

confidence: 99%

Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain.

Perlman

Evans

Afifi

1990

The Journal of Experimental Medicine

120

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SummaryPrevious results suggested that, after intranasal inoculation, mouse hepatitis virus (MHV), a neurotropic coronavirus, entered the central nervous system (CNS) via the olfactory and trigeminal nerves. To prove this hypothesis, the effect of interruption of the olfactory pathway on spread of the virus was studied using in situ hybridization . Unilateral surgical ablation of this pathway prevented spread of the virus via the olfactory tract on the side of the lesion . MHV RNA could be detected, however, at distal sites on the operated side, indicating that the virus spread via well-described circuits involving the anterior commissure from the control (intact) side of the brain . Viral transport via the trigeminal nerve was not affected by removal of the olfactory bulb, showing that the surgical procedure was specific for the olfactory pathway. These results prove conclusively that MHV gains entry to the CNS via a transneuronal route, and spreads to additional sites in the brain via known neuroanatomic pathways.

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Section: Discussionmentioning

confidence: 99%

Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain.

Perlman

Evans

Afifi

1990

The Journal of Experimental Medicine

120

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“…A prominent nodal degradative capacity mainly seems to be important for alpha-motor neurons, which in addition to having long axons with large volume also have their synaptic terminals located external to the blood-brain barrier. Since blood-borne macromolecules, which normally do not penetrate the blood-brain and blood-nerve barrier, may gain entrance to the lower motor neuron perikarya in the spinal cord via retrograde transport from the axon terminals (for reviews, see Griffin and Watson, 1988;Kristensson, 1978Kristensson, ,1982, the observed interneuronal differences in axonal lysosome activity may reflect a higher need for lysosomes in alpha-motor axons than other axon types. In considering that materials that are transported from the most distal parts of the longest cat lumbo-sacral alpha-motor axons, such as substances imbibed at the synaptic terminals, have to pass through 120-150 PNS node-paranode regions on their way to the perikaryon, the total nodal degradative capacity could be of significance in that it might give some protection to the motor neuron perikaryon from being flooded with and perhaps injured by potentially deleterious exogenous molecules and indigestible materials emanating from the distal axon.…”

Section: And Perspectivesmentioning

confidence: 99%

Node-paranode regions as local degradative centres in alpha-motor axons

Gatzinsky

1996

Microsc. Res. Tech.

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Lysosomes play an important role for the maintenance of a normal internal milieu in the cell. In neurons lysosomes are abundant in the perikaryon and dendrites, but have been observed to a much lesser degree in the axon. A general opinion has therefore formed among biologists interested in the nervous system that axonal material destined for degradation has to be transported to the neuronal perikaryon. The lysosomal occurrence and distribution at the level of the axon have, however, not been investigated systematically. This review summarizes recent morphological data based on light, fluorescence, and electron microscopic observations in peripheral nerve fibres of cats and rats providing evidence that node‐paranode regions mainly along the peripheral parts of alpha motor axons, where the axon cross‐section area decreases to 10–25% of internodal values, can control the passage and participate in a lysosome‐mediated degradation of axonally transported materials directed towards the neuronal perikaryon. An important role is played by the paranodal axon‐Schwann cell networks, which are lysosome‐rich entities whereby the Schwann cells can sequester material from the axoplasm of large myelinated peripheral nerve fibres. The networks also seem to serve as depots for axonal waste products. The degradative ability of node‐paranode regions in alpha‐motor axons could be of some significance for the protection of the motor neuron perikarya from being flooded with and perhaps injured by indigestible materials as well as potentially deleterious, exogenous substances imbibed by the axon terminals in the muscle. A similar degradative capacity may not be needed in nerve fibres with synaptic terminals in the CNS where the local environment is regulated by the blood‐brain barrier. © 1996 Wiley‐Liss, Inc.

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“…Lastly, the temporal events of reovirus infection correspond well to analyses of natural poliovirus infection (40,41), allowing for increased transport time within the longer axons of humans. Although both poliovirus and reovirus mount a viremia that can be terminated by antiviral antibody, evidence from reovirus that antibody can prevent neuronal infection (20) and that T3C9 spreads to the CNS through nerves from the intestinal tract supports the concept of neural spread ofpoliovirus to the CNS after extraneural replication (5)(6)(7). Whether poliovirus and encephalitic strains of other enteric viruses do, in fact, penetrate the CNS by means similar to reovirus awaits further investigation.…”

Section: Resultsmentioning

confidence: 99%

“…Virus could potentially enter the nervous system by direct spread from infected plexuses of nerve fibers in the wall of the alimentary tract (5) or from nerve endings in secondarily infected muscle and visceral organs (6,7). Alternatively, virus could gain entry to the bloodstream and then penetrate the nervous system through the meninges or through blood vessel endothelium in sites where the blood-brain barrier may be more permeable (8)(9)(10): the choroid plexus, hypothalamus, and area postrema.…”

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confidence: 99%

Direct spread of reovirus from the intestinal lumen to the central nervous system through vagal autonomic nerve fibers.

Morrison

Sidman

Fields

1991

Proc. Natl. Acad. Sci. U.S.A.

101

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A crucial event in the pathogenesis of sys- A fundamental unresolved issue in systemic infections with viruses entering a host through the gastrointestinal tract is the route by which virus penetrates the central nervous system (CNS) to cause encephalitis (1-4). Virus could potentially enter the nervous system by direct spread from infected plexuses of nerve fibers in the wall of the alimentary tract (5) or from nerve endings in secondarily infected muscle and visceral organs (6, 7). Alternatively, virus could gain entry to the bloodstream and then penetrate the nervous system through the meninges or through blood vessel endothelium in sites where the blood-brain barrier may be more permeable (8-10): the choroid plexus, hypothalamus, and area postrema. For poliovirus, the most well-studied neurotropic enteric virus of humans, the preponderance of opinion currently favors blood-borne spread to the CNS once viremia has commenced (2, 3, 11, 12), but spread by direct peripheral nerve penetration has not been disproven.The mammalian reoviruses are a group of enteric viruses that have been useful in deciphering the genetic basis of viral pathogenesis (13). Reoviruses enter a host from the intestinal lumen through M cells overlying ilea! Peyer's patches (14) and undergo primary replication in the intestine (15,16 The small intestine is innervated primarily by sympathetic and parasympathetic fibers of the autonomic nervous system and by sensory nerve fibers. Neuronal cell bodies of each of these fiber types have an anatomically distinct location that can be observed in histologic sections: parasympathetic in the dorsal motor nucleus of the vagus nerve (DMNV), sympathetic in the intermediolateral cell column of the thoracic and lumbar spinal cord (T4-L2), and sensory in the dorsal root ganglia of the thoracic spinal cord and the nodose ganglia of the vagus nerve (21). We have examined serial sections of brain, spinal cord, and small intestine from newborn mice inoculated perorally with T3C9 to determine the location of initial virus infection in the nervous system. Neurons of the myenteric plexus of the small intestine immediately adjacent to Peyer's patches were initially infected. Subsequently, viral antigen appeared in the CNS in neurons of the DMNV, indicating that serotype 3 reovirus spreads from the intestinal tract directly to regional nerves and then through parasympathetic fibers to the CNS. MATERIALS AND METHODSVirus. Reovirus serotype 3, field isolate strain clone 9 (T3C9; refs. 20 and 22), was derived from laboratory stocks by double plaque purification. Lysates of second-passage stocks grown on L929 mouse fibroblast monolayers were used for virus purification (23).Titer Determination. Virus titer was determined by standard plaque assay (24). Blood samples were frozen and thawed twice, disrupted by sonication, and assayed in duplicate after serial 1:10 dilutions.Inoculations. Purified virions were diluted in endotoxinfree saline (for subcutaneous injections) or distilled water (for peroral inoculation...

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Implications of Axoplasmic Transport for the Spread of Virus Infections in the Nervous System

Cited by 18 publications

References 31 publications

Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain.

Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain.

Node-paranode regions as local degradative centres in alpha-motor axons

Direct spread of reovirus from the intestinal lumen to the central nervous system through vagal autonomic nerve fibers.

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