Lesson 6: Atypical viruses (prions, viroids, virusoids and Satellite Viruses)

Viroids:

• • Viroids are small, infectious agents composed solely of single-stranded RNA, lacking a protein coat. They are smaller than viruses and were first discovered in the early 1970s. Unlike viruses, which are generally much larger and have both protein and nucleic acid components, viroids consist only of non-coding very small circular RNA molecules (246-467 nucleotides) naked and with rod-like or branched structures. They have no protein coat, capsid or envelope.

• • Viroids are obligate intracellular parasites that replicate autonomously and occur as circular and linear forms containing a high degree of base pairing while parasitizing the host transcriptional machinery.
  • Viroids are totally dependent on host cellular RNA polymerases and processing enzymes for their replication.
  • They are categorized into two families: the Avsunviroidae (type species, Avocado sunblotch viroid ASBVd) and the Pospiviroidae, which includes the Potato spindle tuber viroid (PSTVd) and the Tomato chlorotic dwarf viroid (TCDVd).
  • Viroid RNA moves from infected cells into adjacent cells via plasmodesmata and then through the phloem to distant sink organs of its host plant.
  • The transmittance of viroids occurs through grafting, mechanical injury, pollen, seed and/or insects
  • Viroids are derived from introns and do not code for any proteins. They are often ribozymes, characterized by catalytic RNA
  • Diseases: Viroids cause mild to severe diseases in economically significant crops including both herbaceous and woody plants such as for instance, potato spindle tuber, apple, avocado, coconut, grapevine, hop, peach, tomato, citrus exocorts, cucumber pale fruit (generally plants). These infectious RNA molecules can interfere with the normal functioning of host plant cells, leading to symptoms such as stunted growth, leaf deformities, and reduced crop yield.
  • Viroids do not encode proteins; instead, their RNA sequences can fold into complex structures that can catalyze certain biochemical reactions within the host cell. The exact mechanism by which viroids cause disease is not fully understood, but it is thought to involve interactions with host plant RNA and cellular processes.

Virusoids:

• • Virusoids are small, circular RNA molecules that are dependent on helper viruses for their replication. Unlike viroids, which are independent infectious agents, virusoids need the assistance of a helper virus to complete their life cycle. The helper virus provides the necessary machinery for the replication and encapsidation of virusoid RNA.
  • The virusoid RNA itself usually encodes a few essential functions, such as a ribozyme (an RNA molecule with catalytic activity) for self-cleavage, which helps in the release of the virusoid from the longer RNA concatemers produced during replication. Additionally, the virusoid RNA may have sequences that are similar to those found in the helper virus genome, facilitating their interaction.
  • Virusoids are mainly associated with plant viruses, and they have been identified in certain plant virus families. These satellite-like entities are considered dependent or subviral agents because they cannot complete their replication cycle without the presence of a helper virus. The interaction between virusoids and helper viruses can impact the symptoms, pathogenicity, and transmission of the associated plant viruses.

Satellite Viruses:

• • Satellite viruses are small infectious agents that, like virusoids, depend on helper viruses for their replication and propagation. Satellite viruses are characterized by their inability to replicate independently; instead, they require the presence of a helper virus to provide the necessary machinery for their replication and encapsidation.
  • The satellite virus itself is a small, usually single-stranded RNA or DNA molecule that encodes only a few essential functions. These functions typically include signals for replication and packaging, as well as structural elements that allow the satellite to be encapsulated by the coat protein of the helper virus. The satellite virus can interfere with the replication of the helper virus, leading to changes in the symptoms or pathogenicity of the overall infection.
  • Satellite viruses are often classified into two main types based on their genetic material: satellite RNA and satellite DNA. Satellite RNA viruses have an RNA genome, while satellite DNA viruses have a DNA genome. Examples of satellite viruses include satellite tobacco necrosis virus (STNV) and hepatitis delta virus (HDV). HDV has a very small circular RNA genome (~1700 nucleotides) compared to most viruses, although it is somewhat larger than viroids.
  • Similar to virusoids, satellite viruses are associated with plant viruses as well as some animal viruses. They contribute to the complexity of virus-host interactions and can impact the severity of diseases caused by the helper viruses. The study of satellite viruses provides insights into the molecular mechanisms of viral replication, encapsidation, and pathogenesis.

Prions:

• • Prions are unique infectious agents that differ from viruses, viroids, and satellite viruses. Unlike these other entities, prions do not contain genetic material in the form of DNA or RNA. Instead, prions consist of misfolded proteins that can induce the misfolding of normal cellular proteins.
  • The term “prion” is derived from “proteinaceous infectious particle.” Prions are associated with a group of neurodegenerative diseases in animals and humans called transmissible spongiform encephalopathies (TSEs). Examples of TSEs in animals include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and chronic wasting disease (CWD) in deer and elk. In humans, prion diseases include Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), and others.
• Mechanism: 
  • The normal cellular prion protein (PrPC) is found in healthy organisms, particularly in the brain. However, in the presence of misfolded prion protein (PrPSc), which may arise spontaneously or through exposure to infectious prions, the normal protein undergoes a conformational change and adopts the misfolded structure. These misfolded prions can accumulate in the brain, forming aggregates that lead to neurodegeneration.
  • One of the unique and puzzling aspects of prion diseases is their ability to be transmitted horizontally, meaning from one individual to another, or vertically, from one generation to the next, without the involvement of nucleic acids. The misfolded prion protein appears to act as a template, converting normal prion proteins into the abnormal, disease-associated form.
  • Prion diseases have long incubation periods and are usually fatal. Diagnosis is often confirmed postmortem through the examination of brain tissue. Despite significant progress in understanding prion biology, many aspects of prion diseases, including the exact mechanisms of prion propagation and the factors influencing species barriers, remain areas of active research.

The list of identified Prion-Spongiform diseases to date