Scrapie in Mice: Ultrastructural Observations in the Cerebral Cortex

David-Ferreira, J. F.; David-ferreira, K. L.; Gibbs, C. J.; Morris, J. A.

doi:10.3181/00379727-127-32680

Cited by 107 publications

(36 citation statements)

References 3 publications

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“…Additionally, there is one published image of a comparable virus-like array in the perikaryon rather than in postsynaptic boutons (10), further indicating the similarities of the 25-nm particle arrays in brain and cultured cells. Although we did not observe tubular and electron lucent tubular-vesicular/membrane-like components of variable widths in our arrays, as sometimes described in the brain (12), tubular vesicular variants may be due to the elaboration of different components in mature neurons, different stages of particle development, or structures that are not integral to the much denser virus-like particles.…”

Section: Discussionmentioning

confidence: 94%

Cells infected with scrapie and Creutzfeldt–Jakob disease agents produce intracellular 25-nm virus-like particles

Manuelidis

Barquero

et al. 2007

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

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We had repeatedly found ≈25-nm-diameter virus-like particles in highly infectious brain fractions with little prion protein (PrP), and therefore we searched for similar virus-like particles in situ in infected cell lines with high titers. Neuroblastoma cells infected with the 22L strain of scrapie as well as hypothalamic GT cells infected with the FU Creutzfeldt–Jakob disease agent, but not parallel mock controls, displayed dense 25-nm virus-like particles in orthogonal arrays. These particles had no relation to abnormal PrP amyloid in situ , nor were they labeled by PrP antibodies that faithfully recognized rough endoplasmic reticulum membranes and amyloid fibrils, the predicted sites of normal and pathological intracellular PrP. Additionally, phorbol ester stimulated the production of abnormal PrP gel bands by >5-fold in infected N2a + 22L cells, yet this did not increase either the number of virus-like arrays or the infectious titer of these cells. Thus, the 25-nm infection-associated particles could not be prions. Synaptic differentiation and neurodegeneration, as well as retroviruses that populate the rough endoplasmic reticulum of neuroblastoma cells, were not required for particle production. The 25-nm particle arrays in cultured cells strongly resembled those first described in 1968 in synaptic regions of scrapie-infected brain and subsequently identified in many natural and experimental TSEs. The high infectivity of comparable, isolated virus-like particles that show no intrinsic PrP by antibody labeling, combined with their loss of infectivity when nucleic acid–protein complexes are disrupted, make it likely that these 25-nm particles are the causal TSE virions that induce late-stage PrP brain pathology.

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Section: Discussionmentioning

confidence: 94%

Cells infected with scrapie and Creutzfeldt–Jakob disease agents produce intracellular 25-nm virus-like particles

Manuelidis

Barquero

et al. 2007

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

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“…In the initial reports, the observations of Hirano bodies were confined exclusively to the central nervous system. They were confirmed in patients with amyotrophic lateral sclerosis and parkinsonism-dementia (1), in a patient with motor neuron disease (2), in kuru-infected human cerebellum (3), in mice infected experimentally with scrapie (4), and in an adolescent with hepatocerebral degeneration (5). Hirano bodies have also been demonstrated in the peripheral nervous system in a line of mutant hamsters with hind-leg paralysis (6) and in a retroperitoneal ganglioneuroblastomd from a 4-year-old child (7).…”

mentioning

confidence: 89%

Crystalline ribosomes are present in brains from senile humans.

O'Brien¹,

Shelley²,

Towfighi³

et al. 1980

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

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Paracrystalline inclusions known as Hirano bodies characteristically appear in the hippocampal region of the brains of humans exhibiting senile and presenile dementias as well as several other neurodegenerative diseases. We present evidence that the currently accepted model for those structures based on alternating filament sheets is not correct, but that Hirano bodies are stacked sheets of membrane-bound ribosomal particles derived from partially degraded rough endoplasmic reticulum or Nissl substance. Using fluorescence staining with acridine orange and ethidium bromide, we have shown that the bodies contain'RNA.

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“…Until recently, electron microscopy had failed to reveal virus-like structures that were consistently seen in different agent-host combinations or that were observed reproducibly from laboratory to laboratory (Baringer et al, 1981;David-Ferreira et al, 1968;Narang, 1974). However, a finding published in 1981 could have critical importance in the study of the nature of the scrapie agent (Merz et al, 1981).…”

Section: A Filamentous Structure Is Consistently Associated With Scrapiementioning

confidence: 99%