CJD and Scrapie Require Agent‐Associated Nucleic Acids for Infection

@article{Botsios2016CJDAS,
  title={CJD and Scrapie Require Agent‐Associated Nucleic Acids for Infection},
  author={Sotirios Botsios and Laura Manuelidis},
  journal={Journal of Cellular Biochemistry},
  year={2016},
  volume={117}
}
Unlike Alzheimer's and most other neurodegenerative diseases, Transmissible Spongiform Encephalopathies (TSEs) are all caused by actively replicating infectious particles of viral size and density. Different strain‐specific TSE agents cause CJD, kuru, scrapie and BSE, and all behave as latent viruses that evade adaptive immune responses and can persist for years in lymphoreticular tissues. A foreign viral structure with a nucleic acid genome best explains these TSE strains and their endemic and… 

Prion protein PrP nucleic acid binding and mobilization implicates retroelements as the replicative component of transmissible spongiform encephalopathy

TLDR
A strong case is to be made that a second element – retroelement nucleic acid – bound to PrP constitutes the second component necessary to explain the multiple strains of TSE.

Prion Protein PRNP: A New Player in Innate Immunity? The Aβ Connection

TLDR
It is suggested that PRNP, like LL-37 and Aβ, is likely to be a component of the innate immune system, with implications for the pathoetiology of both AD and TSE.

Unraveling Prion Protein Interactions with Aptamers and Other PrP-Binding Nucleic Acids

TLDR
The identification of high-affinity and selective PrP ligands may aid the development of new therapies and diagnostic tools for TSEs, and the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology has proven extremely valuable to investigate PrP–NA interactions.

Data Analyses and new Findings Indicate a Primordial Neurotropic Pathogen Evolved into Infectious Causes of Several CNS Neurodegenerative Diseases

TLDR
These organisms are proposed as hybrid pathogens that express two separate sets of structures and functions: viruslike properties when intracellular, and yet also reproduce as unique prokaryotes when outside the host.

CWD Tuberculosis Found in SpongiformDisease Formerly Attributed to Prions: ItsImplication towards Mad Cow Disease,Scrapie and Alzheimers

TLDR
The present investigation of the TSEs clearly shows cell-wall-deficient (CWD) tubercular mycobacteria present, verified by molecular analysis, ELISA, PCR and microscopy to cause spongiform encephalopathy.

Prokaryotic SPHINX replication sequences are conserved in mammalian brain and participate in neurodegeneration

TLDR
The evolutionary origin, spread, and neuropathology of SPHINX 1.8 REP sequences opens another unanticipated chapter for mammalian symbiotic interactions with environmental microbes.

Reduced Expression of Prion Protein With Increased Interferon-β Fail to Limit Creutzfeldt-Jakob Disease Agent Replication in Differentiating Neuronal Cells

Immortalized uninfected septal (SEP) neurons proliferate but after physiological mitotic arrest they express differentiated neuronal characteristics including enhanced cell-to-cell membrane contacts

Long SARS-CoV-2 nucleocapsid sequences in blood monocytes collected soon after hospital admission

TLDR
Long NCs were positive as early as 2-6 days after hospital admission as validated by sequencing, and Predictably, these cells carried CoV19 to heart and brain educing the late post-viral pathologies now evident.

The “Jekyll and Hyde” Actions of Nucleic Acids on the Prion-like Aggregation of Proteins*

TLDR
How nucleic acid binding might influence protein misfolding for both disease-related and benign, functional prions and why the line between bad and good amyloids might be more subtle than previously thought are discussed.

Prokaryotic SPHINX sequences are conserved in mammalian brain and participate in neurodegeneration

TLDR
To determine if spx concentrated at specific neurons and synapses, and also maintained a conserved pattern of architectural organization in mammals, mouse, rat, hamster, Guinea Pig and human brains were evaluated and cross-species concentration of spx was most outstanding.

References

SHOWING 1-10 OF 47 REFERENCES

Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms

TLDR
To reexamine the intrinsic resistance of TSE agents to denaturation, a paradigm for less resistant viruses and microbes, a rapid and reproducible high yield agent isolation procedure from cultured cells that minimized PrP amyloid and other cellular proteins is developed.

Replication and spread of CJD, kuru and scrapie agents in vivo and in cell culture

TLDR
Profound agent-specific inhibitory effects are also apparent in GT1 cells, and maximal titer plateau in kCJD and FU-CJD differed by 1,000-fold in a cell-based assay, most consistent with a foreign viral structure, rather than an infectious form of host prion protein (PrP-res).

Highly Infectious CJD Particles Lack Prion Protein but Contain Many Viral‐Linked Peptides by LC‐MS/MS

TLDR
A streamlined, high‐yield purification of infectious FU‐CJD mouse brain particles with minimal PrP suggested that new therapies directed at retromer–vesicular trafficking in other neurodegenerative diseases may also counteract late‐onset sCJD PrP amyloid pathology.

A 25 nm virion is the likely cause of transmissible spongiform encephalopathies

TLDR
The development of tissue culture models that support the replication of many different strains of agent and can produce high levels of infectivity are developed, providing new ways to rapidly identify intrinsic viral and strain‐specific molecules so important for diagnosis, prevention, and fundamental understanding.

A rapid accurate culture assay for infectivity in Transmissible Encephalopathies

TLDR
Standardized GT1 assays can be used for direct comparison of different agent strains, and will facilitate the rapid isolation of essential agent components.

Viral particles are required for infection in neurodegenerative Creutzfeldt-Jakob disease.

TLDR
The data strongly implicate a classical viral structure, possibly with no intrinsic PrP, as the CJD infectious agent and preliminary subtraction studies have revealed several CJD-specific nucleic acids.

Proteomic analysis of host brain components that bind to infectious particles in Creutzfeldt‐Jakob disease

TLDR
The infectious particle strategy, which reduces background sequences by >99%, emphasizes host targets for new therapeutic initiatives after host proteins bound with FU‐CJD agent infectious brain particles by proteomic analysis.

Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD

TLDR
The Sphinx sequences uncovered here could have a role in TSE infections despite their apparently symbiotic, low-level persistence in normal cells and tissues, and raise the intriguing possibility that mammals may incorporate more of the prokaryotic world in their cytoplasm than previously recognized.

The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents

TLDR
Primate kuru, a TSE once epidemic in New Guinea, was transmitted to mice expressing normal and ≈8-fold higher levels of murine prion protein (PrP), and the geographic independence of the kuru agent provides additional reasons to explore causal environmental pathogens in these infectious neurodegenerative diseases.

Quantitative recovery of scrapie agent with minimal protein from highly infectious cultures.

TLDR
A streamlined approximately 3-h procedure that yielded full recovery of starting infectivity in fractions with only a few selected protein bands is developed, which may be used to elicit diagnostic antibodies to foreign agent proteins.