Endogenous Viral Etiology of Prion Diseases
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- Centers for Disease Control and Prevention, Atlanta, GA 30333
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- Manuscript
- Date:
- Received 21 October 2009 18:35 UTC; Posted 23 October 2009
- Subjects:
- Microbiology, Neuroscience, Evolutionary Biology
- Abstract:
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of incurable neurodegenerative disorders, including Kuru and Creutzfeldt-Jakob disease in humans, “mad cow” disease in cattle, and scrapie in sheep. This paper presents structural, genetic, and evolutionary evidence supporting an endogenous TSE virus model that integrates the three major traditional views on the nature of TSE pathogens, the conventional virus view, the prion hypothesis, and the virino concept, into a novel conceptual and evolutionary framework. According to this model, the TSE pathogens are symbiotic endogenous viruses that inadvertently produce transmissible viral particles that lack the viral genome and are composed primarily of the viral prion protein (PrP). Production of defective viral particles that contain a partial genome or lack the viral genome entirely is a relatively common event in the life cycle of many viruses. Similar to the normal viral particles, which contain a genome, these defective viral particles can be transmitted to new host cells. Obviously, in the absence of viral genome, these protein-only viral particles cannot establish a productive infection. However, if these viral particles enter a host cell that carries the parental or a related virus and induce the production of similar protein-only particles, then they would appear as self-replicating, protein-only infectious pathogens if mistakenly taken out from the context of the viral life cycle. This misconception, which is rooted into the current dogma of viruses as viral particles, led to the development of the prion theory. The endogenous TSE virus model is consistent with the TSE data and offers solutions to many enigmatic features associated with TSE, including the function of PrP that, despite more than two decades of TSE research conducted primarily within the framework of the prion hypothesis, is still not known. According to the TSE endogenous virus model, PrP is the protein of an endogenous virus that has co-evolved with their vertebrate hosts by providing a protective function against pathogenic viruses. The evidence for the endogenous TSE virus model and for the antiviral protective function of PrP is strong, and they are fully open to additional experimental testing. The endogenous virus model opens the TSE research field to new interpretations and directions, both in basic research and in associated biomedical and public health fields, and could lead to development of new diagnostic and therapeutic approaches.
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Bandea, Claudiu. Endogenous Viral Etiology of Prion Diseases. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3887.1> (2009)
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Claudiu Bandea on 23 October 2009 12:43 UTC
This is one of a series of three papers (1,2,3) that presents a broad, unifying scenario on the origin and evolution of cellular and viral domains, including the origin of life. This scenario challenges the current view about the history of life at the most fundamental level.
Briefly, the first paper, “The Origin and Evolution of Viruses as Molecular Organisms,” questions the current dogma of viruses as viral particles and presents an alternative view about their nature, origin, and evolution (1). In addition to its conceptual implications, the new view about the nature and evolution of viruses has immediate, specific biomedical applications. One of the most pragmatic, potential applications is in a field of transmissible spongiform encephalopathies, which is presented in the second paper, “Endogenous Viral Etiology of Prion Diseases” (2). The third paper, “A Unifying Scenario on the Origin and Evolution of Cellular and Viral Domains,” integrates the new view about the evolution and nature of viruses into a broad, unifying scenario for the evolutionary origin of cellular and viral domains, including the origin of life (3).
Because of the broad topics of these papers, over the last two years, I sent them for review to numerous scientists and research experts in various biomedical fields. As you can see in the Acknowledgements section of these papers, many of these scientists were kind enough to share their thoughts, for which I’m grateful. Here, I would like to address a common concern about the format and the presentation style of these papers.
As mentioned above, the topics addressed in this series are very broad. These topics have been discussed in thousands of publications presenting a myriad of novel ideas, models, and hypotheses. Although the papers in this series are exceedingly long, I could not address, or even mention or reference, many of these previous publications; obviously, this doesn’t do justice to their authors. My intent in this series was to focus on, and outline, what I thought represent novel interpretations, ideas, and models sustaining a broad, unifying scenario on the origin and evolution of cellular and viral domains; this approach might also explain the apparent dogmatic presentation style.
(1) Bandea, Claudiu. The Origin and Evolution of Viruses as Molecular Organisms. Available from Nature Precedings(http://hdl.handle.net/10101/npre.2009.3886.1), 2009
(2) Bandea, Claudiu. Endogenous Viral Etiology of Prion Diseases. Available from Nature Precedings (http://hdl.handle.net/10101/npre.2009.3887.1), 2009
(3) Bandea, Claudiu. A Unifying Scenario on the Origin and Evolution of Cellular and Viral Domains. Available from Nature Precedings (http://hdl.handle.net/10101/npre.2009.3888.1), 2009