6.4 Viroids, Virusoids, and Prions

3 min readjune 18, 2024

, virusoids, and prions are unique infectious agents that challenge our understanding of life. These tiny pathogens lack traditional cellular structures yet can cause devastating diseases in plants and animals.

Unlike viruses, these agents have simpler structures and replication methods. Viroids and virusoids are small RNA molecules, while prions are misfolded proteins. Their ability to replicate and spread without typical genetic material makes them fascinating subjects in microbiology.

Viroids, Virusoids, and Prions

Structure and replication of viroids

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  • Smallest known infectious agents consist solely of a single-stranded, circular RNA molecule without a protein coat, unlike viruses
  • Genome size ranges from 246 to 467 nucleotides (, )
  • Replication occurs in the nucleus of host plant cells
    • Involves the (RdRP) of the host
    • (+) strand RNA acts as a template for synthesizing (-) strand RNA
    • (-) strand RNA then serves as a template for synthesizing new (+) strand RNA
    • Newly synthesized (+) strand RNA molecules are cleaved and circularized to form mature viroids
  • Viroids lack a protein coat, have a much smaller genome, and do not encode any proteins, distinguishing them from viruses
  • Some viroids possess activity, allowing them to catalyze their own cleavage during replication

Virusoids vs satellite viruses

  • Virusoids are small, circular, single-stranded RNA molecules dependent on for replication
    • Genome size ranges from 220 to 388 nucleotides (, )
    • Encapsidated within the coat protein of the helper virus
  • Satellite viruses also depend on helper viruses for replication but have larger genomes (800 to 1,400 nucleotides) and encode their own coat protein (, )
  • Both virusoids and satellite viruses rely on the replication machinery of the helper virus, which provides necessary enzymes like RdRP
  • They compete with the helper virus for replication resources

Prions and neurodegenerative diseases

  • Infectious agents composed solely of misfolded proteins, lacking nucleic acids
    • Misfolded form of the protein denoted as ()
    • Normal cellular form of the protein denoted as
  • Prion replication and propagation involves PrPSc^{Sc} acting as a template, inducing misfolding of normal PrPC^C proteins
    • Misfolded PrPSc^{Sc} proteins aggregate and accumulate in the brain, leading to
  • Prions cause several neurodegenerative diseases in humans and animals ()
    • Human diseases: (CJD), (FFI),
    • Animal diseases: (BSE) in cattle, scrapie in sheep
  • Mechanisms of prion-induced neurodegeneration
    1. Accumulation of misfolded PrPSc^{Sc} proteins leads to plaque formation
    2. Neuronal loss and synaptic dysfunction occur due to toxic effects of misfolded prions
    3. Activation of glial cells and neuroinflammation contribute to disease progression

RNA processing in viroids and virusoids

  • plays a crucial role in the life cycle of some viroids and virusoids
  • Self-cleavage and ligation of RNA molecules are essential for replication and maturation
  • Hammerhead ribozymes found in certain viroids and virusoids catalyze specific RNA cleavage reactions

Key Terms to Review (41)

Amyloid: Amyloid is a type of protein that can misfold and aggregate into insoluble, fibrillar structures. These amyloid deposits can accumulate in various tissues and organs, leading to the development of several diseases known as amyloidoses.
Avocado sunblotch viroid: Avocado sunblotch viroid (ASBVd) is a pathogenic RNA molecule that infects avocado trees, causing significant crop damage. It is one of the smallest known pathogens and does not encode any proteins.
Bovine Spongiform Encephalopathy: Bovine spongiform encephalopathy (BSE), commonly known as 'mad cow disease', is a rare and fatal neurodegenerative disorder that affects cattle. It is classified as a prion disease, which are a group of progressive conditions that affect the structure and function of the brain and nervous system.
Chronic wasting disease: Chronic wasting disease (CWD) is a fatal, transmissible spongiform encephalopathy affecting cervids like deer, elk, and moose. It is caused by misfolded prion proteins that lead to severe neurological degeneration.
Chrysanthemum Stunt Viroid: The chrysanthemum stunt viroid is a small, circular, single-stranded RNA molecule that lacks a protein coat and is the causative agent of a disease that stunts the growth of chrysanthemum plants. As a member of the Viroids category, it represents a unique class of infectious pathogens that are distinct from both viruses and prions.
Creutzfeldt-Jakob disease: Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disorder caused by prions. It leads to rapidly progressive dementia and other neurological symptoms.
Diener: Diener is a term used to describe a person who works in laboratory settings, often assisting with the handling of acellular pathogens like viroids, virusoids, and prions. They play a crucial role in the preparation and management of biological samples for research and diagnostic purposes.
Fatal familial insomnia: Fatal familial insomnia (FFI) is a rare inherited prion disease that affects the thalamus, leading to progressively worsening insomnia and other neurological symptoms. It is invariably fatal, typically resulting in death within 12-18 months after symptoms appear.
Fatal Familial Insomnia: Fatal Familial Insomnia (FFI) is a rare and fatal neurodegenerative disorder characterized by a progressive inability to sleep, leading to severe insomnia, autonomic dysfunction, and ultimately, death. This term is particularly relevant in the context of 6.4 Viroids, Virusoids, and Prions, as FFI is caused by a specific type of infectious agent known as a prion.
Gerstmann-Straussler-Scheinker disease: Gerstmann-Straussler-Scheinker disease (GSS) is a rare, inherited prion disease characterized by progressive neurodegeneration. It is caused by mutations in the PRNP gene which encodes the prion protein.
Helper viruses: Helper viruses are viruses that provide essential functions missing in defective viruses, allowing them to replicate. They often assist viroids and virusoids, which lack the necessary machinery for independent replication.
Hepatitis B virus (HBV): Hepatitis B virus (HBV) is a DNA virus that infects the liver, leading to inflammation and potentially chronic liver disease. It is part of the Hepadnaviridae family and can be transmitted via blood, sexual contact, or from mother to child during childbirth.
Hepatitis delta virus (HDV): Hepatitis Delta Virus (HDV) is a defective RNA virus that requires the presence of Hepatitis B Virus (HBV) to replicate. HDV causes severe liver disease and can lead to cirrhosis and liver cancer.
Hepatitis Delta Virusoid: A hepatitis delta virusoid is a subviral infectious agent that consists of a small, circular, single-stranded RNA molecule encapsulated within the envelope proteins of the hepatitis B virus. It is considered a virusoid, a distinct class of infectious agents that rely on a helper virus to complete their life cycle.
Kuru: Kuru is a rare, fatal neurodegenerative disorder caused by prions, primarily affecting the Fore people of Papua New Guinea. It is transmitted through the practice of ritualistic cannibalism.
Kuru: Kuru is a rare, fatal, and incurable neurodegenerative disorder that primarily affects the nervous system. It is caused by infectious proteins called prions and is closely associated with the topics of viroids, virusoids, and acellular diseases of the nervous system.
Mad cow disease: Mad cow disease, or bovine spongiform encephalopathy (BSE), is a fatal neurodegenerative disease in cattle caused by prions. It leads to brain damage and is transmissible to humans as variant Creutzfeldt-Jakob disease (vCJD).
Neurodegeneration: Neurodegeneration is the progressive loss of structure or function of neurons, including the death of neurons. It is a key feature of various neurological disorders, such as Alzheimer's disease, Parkinson's disease, and prion diseases, and can be caused by a variety of factors, including genetic mutations, environmental toxins, and infectious agents.
Peach latent mosaic viroid: Peach latent mosaic viroid (PLMVd) is a small, circular RNA molecule that infects peach trees, leading to latent infections or mosaic symptoms on leaves. It does not encode proteins and relies entirely on the host's cellular machinery for replication.
Potato spindle tuber viroid: The potato spindle tuber viroid (PSTVd) is a small, circular, single-stranded, non-coding RNA molecule that infects potato plants and other members of the Solanaceae family. As a viroid, it lacks the protein coat found in viruses and relies solely on its RNA genome to replicate and spread within the host plant.
Potato tuber spindle disease: Potato tuber spindle disease is a plant disease caused by a viroid, which affects potatoes leading to spindle-shaped tubers. It results in significant yield loss and quality degradation in affected crops.
Prion: Prions are infectious proteins that cause abnormal folding of specific normal cellular proteins called prion proteins, primarily found in the brain. These misfolded proteins can lead to brain damage and are responsible for a variety of neurodegenerative diseases.
Prion: A prion is an infectious agent composed primarily of a misfolded protein that can induce other, normally folded versions of the same protein to also misfold. Prions are responsible for a group of rare and fatal neurodegenerative disorders known as transmissible spongiform encephalopathies (TSEs).
PrP$^{Sc}$: PrP$^{Sc}$ is the abnormal, infectious isoform of the prion protein (PrP) that is responsible for the development of prion diseases. It is the causative agent of transmissible spongiform encephalopathies (TSEs), a group of fatal neurodegenerative disorders affecting both humans and animals.
PrP$^C$: PrP$^C$ is the cellular prion protein, a normal, harmless form of the prion protein found in the body. It is a key component in the study of prions, which are infectious agents that can cause neurodegenerative diseases like Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE), also known as 'mad cow' disease.
Prusiner: Stanley B. Prusiner is an American neurologist and biochemist who discovered prions, infectious agents composed of protein that cause neurodegenerative diseases.
Ribozyme: A ribozyme is a type of RNA molecule that can catalyze chemical reactions, similar to the way proteins called enzymes catalyze reactions. Ribozymes are found in various biological contexts, including viroids, virusoids, and prions, where they play important roles in the replication and regulation of these infectious agents.
RNA Splicing: RNA splicing is the process by which introns (non-coding regions) are removed from a precursor messenger RNA (pre-mRNA) molecule, and the remaining exons (coding regions) are joined together to form a mature, functional mRNA molecule. This process is essential for the proper expression of genes in eukaryotic organisms, including those involved in the topics of viroids, virusoids, and the structure and function of RNA.
RNA-dependent RNA polymerase: RNA-dependent RNA polymerase (RdRp) is an enzyme that catalyzes the synthesis of RNA from an RNA template. It is a critical component in the replication and transcription of viral genomes, particularly for RNA viruses, as it allows them to replicate their genetic material within the host cell.
Satellite Panicum Mosaic Virus: Satellite Panicum Mosaic Virus (SPMV) is a small, single-stranded RNA virus that requires the presence of a helper virus, Panicum Mosaic Virus (PMV), to replicate and infect host plants. It is classified as a virusoid, a type of subviral agent that depends on a helper virus for its propagation.
Satellite RNA: Satellite RNA are small, non-coding RNA molecules that depend on a helper virus for replication and encapsidation. They often modify the symptoms of the host plant's viral disease.
Satellite Tobacco Necrosis Virus: Satellite tobacco necrosis virus (STNV) is a small, single-stranded RNA virus that requires the presence of a helper virus, such as the tobacco necrosis virus, to replicate and infect host cells. It is classified as a virusoid, a type of subviral agent that is dependent on a helper virus for its propagation.
Scrapie: Scrapie is a fatal, neurodegenerative disease that affects sheep and goats. It is the earliest known form of a group of diseases called transmissible spongiform encephalopathies (TSEs), which are caused by abnormal prion proteins that can induce other normal prion proteins to misfold.
Sobemoviruses: Sobemoviruses are a group of single-stranded RNA viruses that primarily infect plants, causing significant agricultural damage. They are known for their small genome size and ability to be transmitted by insect vectors.
Tomato planta macho viroid: Tomato planta macho viroid (TPMVd) is a small, circular RNA molecule that infects tomato plants, causing stunted growth and other developmental abnormalities. It lacks a protein coat and relies entirely on the host's cellular machinery for replication.
Transmissible Spongiform Encephalopathies: Transmissible spongiform encephalopathies (TSEs) are a group of rare, fatal neurodegenerative disorders caused by abnormally folded proteins called prions. These disorders primarily affect the brain and nervous system, leading to sponge-like changes in brain tissue.
Velvet Tobacco Mottle Virusoid: The velvet tobacco mottle virusoid is a type of subviral infectious agent that is smaller and simpler in structure than a virus. It consists of a single, circular, highly base-paired, non-coding RNA molecule that can replicate autonomously within the host cell, without the need for a viral genome or viral-encoded proteins.
Viroid: A viroid is a small, circular, and infectious RNA molecule that lacks a protein coat and is capable of replicating within the cells of certain plants. Viroids are the smallest known plant pathogens and are distinct from viruses, which have a protein coat and more complex genetic material.
Viroids: Viroids are small, circular RNA molecules that infect plants and can cause various diseases. Unlike viruses, they lack a protein coat and do not code for proteins.
Virusoid: Virusoids are subviral particles composed of circular single-stranded RNA that depend on helper viruses for replication. They do not encode proteins and rely entirely on the host's cellular machinery and a helper virus for their lifecycle.
Virusoid: A virusoid is a small, circular, single-stranded RNA molecule that is similar to a virus but lacks the ability to self-replicate. Virusoids are dependent on the host cell's machinery and a helper virus for their replication and propagation, making them a unique class of infectious agents distinct from viruses, viroids, and prions.
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