Immune system-dependent and -independent replication of the scrapie agent

Lasmézas, Corinne Ida; Cesbron, Jean‐Yves; Deslys, Jean‐Philippe; Demaimay, Rémi; Adjou, Karim; Rioux, Renee A.; Lemaire, Catherine; Locht, Camille; Dormont, Dominique

doi:10.1128/jvi.70.2.1292-1295.1996

Cited by 130 publications

(40 citation statements)

References 37 publications

(39 reference statements)

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“…Neither FDCs nor CD11c + DCs were essential for neuroinvasion in mice perorally challenged with high doses of RML scrapie agent [72]. This observation is consistent with previous findings in rodent models of parenteral infection where reduced susceptibility of immunodeficient mice to TSE challenge was overcome by inoculation with high doses of infectivity [73][74][75][76]. Additionally, certain TSE agents, such as the hamster-adapted DY strain of TME, can induce a non-LRS-related neuroinvasion after inoculation into highly innervated peripheral tissues, such as the tongue [77].…”

Section: Central Nervous System Brain and Spinal Cordsupporting

confidence: 91%

The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies

2007

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Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that are caused by unconventional pathogens and affect the central nervous system of animals and humans. Several different forms of these diseases result from natural infection (i.e. exposure to transmissible spongiform encephalopathy agents or prions, present in the natural environment of the respective host). This holds true also for scrapie in sheep, bovine spongiform encephalopathy in cattle, chronic wasting disease in elk and deer, or variant Creutzfeldt–Jakob disease in humans, all of which are assumed to originate predominantly from peroral prion infection. This article intends to provide an overview of the current state of knowledge on the spread of scrapie, chronic wasting disease, bovine spongiform encephalopathy and variant Creutzfeldt–Jakob disease agents through the body in naturally affected hosts, and in model animals experimentally challenged via the alimentary tract. Special attention is given to the tissue components and spreading pathways involved in the key stages of prion routing through the body, such as intestinal uptake, neuroinvasion of nerves and the central nervous system, and centrifugal spread from the brain and spinal cord to peripheral sites (e.g. sensory ganglia or muscles). The elucidation of the pathways and mechanisms by which prions invade a host and spread through the organism can contribute to efficient infection control strategies and the improvement of transmissible spongiform encephalopathy diagnostics. It may also help to identify prophylactic or therapeutic approaches that would impede naturally acquired transmissible spongiform encephalopathy infections.

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Section: Central Nervous System Brain and Spinal Cordsupporting

confidence: 91%

The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies

2007

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“…80 Upon reconstitution of SCID mice with wild-type spleen cells, susceptibility to scrapie is restored after peripheral infection. 81 These findings suggest that components of the immune system are required for efficient transfer of prions from the site of peripheral infection to the CNS.…”

Section: Spread Of Prions From Extracerebral Sites To the Cnsmentioning

confidence: 98%

Prions: Pathogenesis and Reverse Genetics

Aguzzi

Klein

Montrasio

et al. 2000

Annals of the New York Academy of Sciences

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Spongiform encephalopathies are a group of infectious neurodegenerative diseases. The infectious agent that causes transmissible spongiform encephalopathies was termed prion by Stanley Prusiner. The prion hypothesis states that the partially protease‐resistant and detergent‐insoluble prion protein (PrPsc) is identical with the infectious agent, and lacks any detectable nucleic acids. Since the latter discovery, transgenic mice have contributed many important insights into the field of prion biology. The prion protein (PrPc) is encoded by the Prnp gene, and disruption of Prnp leads to resistance to infection by prions. Introduction of mutant PrPc genes into PrPc‐deficient mice was used to investigate structure‐activity relationships of the PrPc gene with regard to scrapie susceptibility. Ectopic expression of PrPc in PrPc knockout mice proved a useful tool for the identification of host cells competent for prion replication. Finally, the availability of PrPc knockout and transgenic mice overexpressing PrPc allowed selective reconstitution experiments aimed at expressing PrPc in neurografts or in specific populations of hemato‐ and lymphopoietic cells. The latter studies helped in elucidating some of the mechanisms of prion spread and disease pathogenesis.

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“…Moreover, intraperitoneal infection does not lead to replication of prions in the spleen nor to cerebral scrapie in mice with severe combined immunodeficiency (SCID) whose FDC are thought to be functionally impaired (95). Reconstitution of SCID mice with wild-type spleen cells restores susceptibility to scrapie after peripheral infection (81). These findings suggest that components of the immune system are required for efficient transfer of prions from the site of peripheral infection to the CNS.…”

Section: Spread Of Prions From Extracerebral Sites To the Cnsmentioning

confidence: 99%

Transgenic and Knockout Mice in Research on Prion Diseases

Raeber¹,

Brandner²,

Klein³

et al. 1998

Brain Pathology

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Since the discovery of the prion protein (PrP) gene more than a decade ago, transgenetic investigations on the PrP gene have shaped the field of prion biology in an unprecedented way. Many questions regarding the role of PrP in susceptibility of an organism exposed to prions have been elucidated. For example mice with a targeted disruption of the PrP gene have allowed the demonstration that an organism that lacks PrPc is resistant to infection by prions. Reconstitution of these mice with mutant PrP genes allowed investigations on the structure-activity relationship of the PrP gene with regard to scrapie susceptibility. Unexpectedly, transgenic mice expressing PrP with specific amino-proximal truncations spontaneously develop a neurologic syndrome presenting with ataxia and cerebellar lesions. A distinct spontaneous neurologic phenotype was observed in mice with internal deletions in PrP. Using ectopic expression of PrP in PrP knockout mice has turned out to be a valuable approach towards the identification of host cells that are capable of replicating prions. Transgenic mice have also contributed to our understanding of the molecular basis of the species barrier for prions. Finally, the availability of PrP knockout mice and transgenic mice overexpressing PrP allows selective reconstitution experiments aimed at expressing PrP in neurografts or in specific populations of hemato- and lymphopoietic cells. Such studies have shed new light onto the mechanisms of prion spread and disease pathogenesis.

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Immune system-dependent and -independent replication of the scrapie agent

Cited by 130 publications

References 37 publications

The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies

The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies

Prions: Pathogenesis and Reverse Genetics

Transgenic and Knockout Mice in Research on Prion Diseases

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