Experimental rabies: Ultrastructural quantitative analysis of the changes in the sciatic nerve

Teixeira, Fernanda; Aranda, Françesco; Castillo, S Miguel; Pérez, Mónica; Peón, L. Del; Hernández, Oswaldo

doi:10.1016/0014-4800(86)90017-1

Cited by 9 publications

(6 citation statements)

References 14 publications

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“…Minguetti and colleagues reported axonal degeneration and demyelination in both peripheral and cranial nerves of rodents inoculated with RV (181,182). Examination of mouse sciatic nerves inoculated with RV revealed that axonal degeneration mainly occurred in myelinated axons (183). In another study, a detailed analysis of brain pathology in RV-infected mice found fragmentation, beading and vacuolation of axons along with little or no signs of apoptosis, suggesting that axonal dysfunction might play a large role in the development of rabies (184).…”

Section: Axonal Damage and Degenerationmentioning

confidence: 99%

Virus-induced neuronal dysfunction and degeneration

2009

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In general, virus infections of the brain are rather rare in the immune competent host. However, neurotropic viruses have developed mechanisms to exploit weaknesses in immunological defense mechanisms that eventually allow them to reach and infect CNS neurons. Once in the CNS, these viruses can induce significant neuronal dysfunction and degeneration of specific neuronal populations, sometimes leading to devastating, life-threatening consequences for the host. Here, we examine viruses with the ability to infect neurons and their resulting pathologies, their modes of entry to the CNS, and the cellular and molecular alterations that these viruses induce in neuronal cells. We also discuss the importance of various pathogenic events associated with viral infection of neurons and elaborate on the implications of recent findings suggesting that neuronal cells affected by viruses undergo a "dying back" pattern of degeneration. Finally, findings of virus-induced alterations in kinase activity are discussed in the context of recent evidence linking abnormalities in kinase signaling to the pathogenesis of major human neurodegenerative conditions.

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Section: Axonal Damage and Degenerationmentioning

confidence: 99%

Virus-induced neuronal dysfunction and degeneration

2009

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“…Myelinating SCs are peripheral neuroglia, which form the myelin sheath around axons of motor and sensory neurons and, like oligodendrocytes in the CNS, are involved in saltatory conduction and trophic support for neurons (reviewed in [ 52 ]). In peripheral nerves, RABV infection was associated with axon demyelination [ 14 , 38 , 39 , 56 , 58 ]. T-lymphocyte-dependent immune pathogenesis was identified to be causative for RABV-mediated neurotic paralysis, the disintegration of myelin sheaths, and the degeneration of axons [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although there are indications that SCs are somehow affected by RABV infections [ 14 , 38 , 39 , 56 , 58 ], evidence for direct RABV infection of SCs in the PNS is lacking. While released RABV particles were detected at nodes of Ranvier (known as myelin-sheath gaps occurring along a myelinated axon [ 41 ]) and between axonal and SC plasma membranes [ 31 , 42 , 43 ], only once infection of SCs is described [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

Neuroglia infection by rabies virus after anterograde virus spread in peripheral neurons

Potratz

Zaeck

Weigel

et al. 2020

acta neuropathol commun

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The highly neurotropic rabies virus (RABV) enters peripheral neurons at axon termini and requires long distance axonal transport and trans-synaptic spread between neurons for the infection of the central nervous system (CNS). Recent 3D imaging of field RABV-infected brains revealed a remarkably high proportion of infected astroglia, indicating that highly virulent field viruses are able to suppress astrocyte-mediated innate immune responses and virus elimination pathways. While fundamental for CNS invasion, in vivo field RABV spread and tropism in peripheral tissues is understudied. Here, we used three-dimensional light sheet and confocal laser scanning microscopy to investigate the in vivo distribution patterns of a field RABV clone in cleared high-volume tissue samples after infection via a natural (intramuscular; hind leg) and an artificial (intracranial) inoculation route. Immunostaining of virus and host markers provided a comprehensive overview of RABV infection in the CNS and peripheral nerves after centripetal and centrifugal virus spread. Importantly, we identified non-neuronal, axon-ensheathing neuroglia (Schwann cells, SCs) in peripheral nerves of the hind leg and facial regions as a target cell population of field RABV. This suggests that virus release from axons and infected SCs is part of the RABV in vivo cycle and may affect RABV-related demyelination of peripheral neurons and local innate immune responses. Detection of RABV in axon-surrounding myelinating SCs after i.c. infection further provided evidence for anterograde spread of RABV, highlighting that RABV axonal transport and spread of infectious virus in peripheral nerves is not exclusively retrograde. Our data support a new model in which, comparable to CNS neuroglia, SC infection in peripheral nerves suppresses glia-mediated innate immunity and delays antiviral host responses required for successful transport from the peripheral infection sites to the brain.

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“…Myelinating SCs are peripheral neuroglia, which form the myelin sheath around axons of motor and sensory neurons and, like oligodendrocytes in the CNS, are involved in saltatory conduction and trophic support for neurons (reviewed in [51]). In peripheral nerves, RABV infection was associated with axon demyelination [37,38,57,14,55]. T-lymphocyte-dependent immune pathogenesis was identified to be causative for RABV-mediated neurotic paralysis, the disintegration of myelin sheaths, and the degeneration of axons [65].…”

Section: Discussionmentioning

confidence: 99%

Neuroglia Infection by Rabies Virus after Anterograde Virus Spread in Peripheral Neurons

Potratz

Zaeck

Weigel

et al. 2020

Preprint

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The highly neurotropic rabies virus (RABV) enters peripheral neurons at axon termini and requires long distance axonal transport and trans-synaptic spread between neurons for the infection of the central nervous system (CNS). Whereas laboratory strains are almost exclusively detected in neurons, recent 3D imaging of field RABV-infected brains revealed an remarkably high proportion of infected astroglia, indicating that in contrast to attenuated lab strains highly virulent field viruses are able to suppress astrocyte mediated innate immune responses and virus elimination pathways. While fundamental for CNS invasion, in vivo field RABV spread and tropism in peripheral tissues is understudied. Here, we used three-dimensional light sheet and confocal laser scanning microscopy to investigate the in vivo distribution patterns of a field RABV clone in cleared high-volume tissue samples after infection via a natural (intramuscular; hind leg) and an artificial (intracranial) inoculation route. Immunostaining of virus and host markers provided a comprehensive overview of RABV infection in the CNS and peripheral nerves after centripetal and centrifugal virus spread. Importantly, we identified non-neuronal,axon-ensheathing neuroglia (Schwann cells, SCs) in peripheral nerves of the hind leg and facial regions as a target cell population of field RABV. This suggest that virus release from axons and infected SCs is part of the RABV in vivo cycle and may affect RABV-related demyelination of peripheral neurons and local innate immune responses. Detection of RABV in axon surrounding myelinating SCs after i.c. infection further provided evidence for anterograde spread of RABV, highlighting that RABV axonal transport and spread of infectious virus in peripheral nerves is not exclusively retrograde. Our data support a new model in which, comparable to CNS neuroglia, SC infection in peripheral nerves suppresses glia-mediated innate immunity and delays antiviral host responses required for successful transport from the peripheral infection sites to the brain.

show abstract

Experimental rabies: Ultrastructural quantitative analysis of the changes in the sciatic nerve

Cited by 9 publications

References 14 publications

Virus-induced neuronal dysfunction and degeneration

Virus-induced neuronal dysfunction and degeneration

Neuroglia infection by rabies virus after anterograde virus spread in peripheral neurons

Neuroglia Infection by Rabies Virus after Anterograde Virus Spread in Peripheral Neurons

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