Non-cellular infectious agents
In microbiology, alongside classical (canonical) viruses, a distinct group of infectious molecules is distinguished, which includes prions and viroids. The main feature of these pathogens lies in their extremely simple and atypical structure.
Normally, the human body and many animals constantly contain the normal prion protein (designated as $PrP^c$). This normal protein is not pathogenic; it performs important regulatory functions in cells. However, under certain conditions, this endogenous protein is capable of transforming into a lethal infectious agent.
Pathogenesis mechanism (conformational diseases)
Diseases caused by prions belong to the category of so-called conformational diseases. This means that the pathogenesis is based not on the destruction of cells by toxins or the replication of a classical virus, but on the alteration of the spatial structure of the protein itself.
The development of the pathology includes the following stages:
- The infectious agent is a protein with an altered spatial configuration. A gross disruption of the normal tertiary or quaternary structure occurs within it.
- The pathological prion enters the organism or is formed spontaneously within it.
- Physical contact occurs between the altered infectious prion and the normal cellular protein $PrP^c$.
- This contact triggers a chain reaction: the normal protein changes its conformation and transforms itself into a pathological prion.
Thus, the infectious process is sustained by the continuous restructuring of the body's own proteins according to the template of the pathological agent.
Genetic aspects and causes
Despite the fact that prions do not contain their own nucleic acids, their existence is closely tied to the host's genetic apparatus.
- Coding: The structure of the normal precursor of the prion protein is encoded in human DNA.
- Localization: The gene responsible for the synthesis of this protein (the $PrP$ gene) is located on the short arm of chromosome 20.
The transition of the normal protein into the infectious form can be triggered by two main causes. First, this can happen as a result of a genetic mutation in the $PrP$ gene itself. Second, the transformation process can begin as a result of external infection, when an already altered pathological molecule enters the body from the outside.
Clinical presentation and cellular consequences
Clinical classification groups prion diseases under transmissible spongiform encephalopathies. This name accurately reflects the nature of the damage to body tissues.
During the development of the disease, the pathological protein begins to accumulate in large quantities directly inside neurons. The cytopathic effect of prion infection is highly specific: the affected cells of the nervous system acquire a characteristic 'spongiform' appearance (vacuolization). The consequence of such massive neuronal destruction is the development of extremely severe neurological disorders of a progressive nature.
The most well-known examples of prion pathologies in humans are:
- Creutzfeldt-Jakob disease;
- Kuru disease.
Viroids: fundamental differences
For a complete understanding of non-cellular agents, it is important to distinguish prions from viroids. Viroids are infectious agents that are close to viruses but possess an even more primitive structure.
- Structure: Unlike prions (which consist only of protein), viroids are small circular supercoiled RNA molecules.
- Envelope: The key difference between viroids and classical viruses lies in the complete absence of a protein coat (capsid).
- Targets: Unlike prions, which affect the nervous system of animals and humans, viroids cause diseases exclusively in plants.
Briefly: answers to topical questions
What human diseases are caused by prions?
Human prion diseases belong to the group of transmissible spongiform encephalopathies. These include:
- Creutzfeldt-Jakob disease, which has sporadic, hereditary, and iatrogenic forms.
- Kuru disease.
- Gerstmann-Sträussler-Scheinker syndrome — a hereditary pathology with dementia, muscle hypotonia, and bulbar symptoms.
- Fatal familial insomnia — an autosomal dominant disease with progressive insomnia.
- Amyotrophic leukospongiosis.
What are the transmission routes of prion infections to humans?
Transmission of prion infections to humans occurs via acquired and hereditary routes. The following main mechanisms of infection are distinguished:
- Alimentary route — consumption of infected animal-derived products and dietary supplements made from raw organs of cattle.
- Artificial (iatrogenic) route — infection via medical procedures. This includes blood transfusion, organ and tissue transplantation, administration of animal-derived medications, and the use of insufficiently processed surgical instruments.
- Hereditary route — transmission of the mutant gene in an autosomal dominant manner.
What methods are used for the laboratory diagnosis of prion infections?
Laboratory diagnosis of prion infections is based on a combination of pathomorphological, immunochemical, and molecular genetic methods. Reliable confirmation of the diagnosis is possible only by examining a CNS tissue biopsy.
- Pathohistological method — detection of spongiform changes in brain tissue, astrocytosis, and amyloid staining in the absence of inflammatory infiltrates.
- Immunochemical methods — detection of protein markers in cerebrospinal fluid using enzyme-linked immunosorbent assay (ELISA) and immunoblotting with monoclonal antibodies.
- Molecular genetic methods — performing genetic analysis of the prion gene and PCR to detect the prion protein.
What is the resistance of prions to physical and chemical sterilization methods?
Prions are extremely resistant to standard physical and chemical factors, including high temperature, radiation, formaldehyde, $\beta$-propiolactone, and proteolysis. Conventional sterilization regimens are ineffective against them. Harsh conditions are used for prion inactivation:
- Autoclaving — at 134 °C for 30 minutes or at 121 °C for 4 hours (with the addition of 1N NaOH).
- Chemical treatment — using bleach combined with 1N NaOH with a 1-hour exposure time.
- Physical method — complete incineration of infected materials.
What specific functions does the normal prion protein (PrPc) perform in a healthy organism?
In a healthy organism, the normal cellular prion protein ($PrP^c$) performs a number of important regulatory functions. Its specific tasks include:
- Regulation of nerve impulse transmission — participation in the normal functioning of the central nervous system.
- Regulation of circadian rhythms — control of the body's biological clock.
- Regulation of copper metabolism — maintaining copper homeostasis in CNS tissues.
- Regulation of stem cell division — control of bone marrow stem cell proliferation.
For quick memorization: PRIONS are PROteins (proteins causing spongiform encephalopathy in humans and animals), while VIROIDS are naked VIrus-like RNA (causing diseases only in plants).
Class and exam questions
Do prions contain genetic material (DNA or RNA)?
No, prions are completely devoid of nucleic acids. They are exclusively infectious protein particles with an altered spatial configuration.
What is the main mechanism of development of prion diseases?
The pathogenesis is based on conformational changes. Contact of the altered infectious prion with the normal body protein ($ ext{PrP}^ ext{c}$) leads to the transformation of the normal protein into the pathological one.
Where is the gene encoding the normal prion protein localized?
The normal protein is encoded by the $ ext{PrP}$ gene, which is localized on the short arm of the 20th human chromosome.
What cytopathic effect is characteristic of prion infections?
The accumulation of the pathological protein inside neurons gives the cell a characteristic "spongiform" appearance, which leads to severe neurological disorders.
What else to study on this topic
- Detailed mechanism of transformation of the normal $ ext{PrP}^ ext{c}$ protein into the pathological form
- Specific neurological disorders in transmissible spongiform encephalopathies
- Creutzfeldt-Jakob disease: clinical presentation and epidemiology
- History of the discovery of Kuru disease and its association with cannibalism
- The role of $ ext{PrP}$ gene mutations on the 20th chromosome in the development of hereditary forms of the disease
- Life cycle of viroids: how circular RNA causes plant pathology
Study the full topic in the «Microbiology» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Prions" and 4,383 other subjects
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 141 video lectures on the subject
Other topics in the section "Morphology and Classification of Microbes"
Free video lessons: microbiologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.