The virino is a
hypothetical
A hypothesis (plural hypotheses) is a proposed explanation for a phenomenon. For a hypothesis to be a scientific hypothesis, the scientific method requires that one can test it. Scientists generally base scientific hypotheses on previous obser ...
infectious
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
particle that was once theorized to be the cause of
scrapie
Scrapie () is a fatal, degenerative disease affecting the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), and as such it is thought to be caused by a prion. Scrapie has been known since ...
and other
degenerative disease
Degenerative disease is the result of a continuous process based on degenerative cell changes, affecting tissues or organs, which will increasingly deteriorate over time.
In neurodegenerative diseases, cells of the central nervous system stop wor ...
s of the central
nervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
; it was thought to consist of
nucleic acid
Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...
s in a protective coat of host cell
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s. The hypothesis was never widely accepted, and the causative agents responsible for these diseases are now widely accepted to be
prion
Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...
s.
Origin of the concept
The virino was described partially to protect the
central dogma of molecular biology
The central dogma of molecular biology is an explanation of the flow of genetic information within a biological system. It is often stated as "DNA makes RNA, and RNA makes protein", although this is not its original meaning. It was first stated by ...
, which was threatened by the existence of a series of degenerative neurological TSE diseases including
kuru
Kuru may refer to:
Anthropology and history
* Kuru (disease), a type of transmissible spongiform encephalopathy associated with the cannibalistic funeral practices of the Fore people
* Kuru (mythology), part of Meithei mythology
* Kuru Kingdom, ...
,
CJD, scrapie in sheep, and
BSE
BSE may refer to:
Medicine
* Bovine spongiform encephalopathy, also known as mad cow disease, a neurodegenerative disease of cattle
* Breast self-examination
Stock exchanges
* Bahrain Stock Exchange, Bahrain
* Baku Stock Exchange, Azerbaijan
* B ...
in cattle. The central dogma states that nucleic acids act as the information carriers, and
DNA and
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
make proteins. Proteins alone cannot make DNA. However, studies searching for the transmission agent of scrapie and other TSEs have failed to culture
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
, and tests attacking nucleic acids strands have little effect on the infectivity of TSE solutions. These failures largely rule out a
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
as the infective agent. Experiments using
electron
The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary particles because they have no kn ...
beams designed to disrupt large
molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
s have been performed to investigate the size of the agent show that it is very small: much smaller than the smallest known virus.
The virino also has the benefit of explaining the traits of TSEs which resemble nucleic acids: for example, their occurrence in strains, which positively indicates the TSE agent is information carrying, and not merely a
toxin
A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...
.
History of description
In 1971,
Dickinson, AG and
Meikle, VM provided a hypothesis for the replication of the scrapie agent. This hypothesis was based on the discovery of a single autosomal
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
controlling the scrapie incubation period in
mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
and on observations about strains of the scrapie agent. They dubbed the gene ''sinc'' for scrapie incubator. This hypothesis proposed that the gene products of each sinc
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
contributed to a multimeric protein structure, which then formed a 'replication site' for the scrapie agent. The replication of the agent would depend on how the particular strain interacted with the replication site and of what the site was composed. The fact that different strains of scrapie were known had suggested the agent was similar to conventional viruses in that it carried a
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
composed of nucleic acids. Thus, variants could arise during
incubation, giving rise to new strains. No host-encoded properties were found to determine scrapie agent strain differences. This was thought to prove that the genome of the agent could vary independently and, although replicated by normal host mechanisms, was not coded by the host. The term 'virino' was coined to reflect the small size,
immunological neutrality, and virus-like nature of the infectious particles.
Thus, in the nucleotide model proposed by Dickinson, AG, and
Outram, GW in 1979, the
lifecycle
Life cycle, life-cycle, or lifecycle may refer to:
Science and academia
* Biological life cycle, the sequence of life stages that an organism undergoes from birth to reproduction ending with the production of the offspring
*Life-cycle hypothesis ...
of the scrapie agent included a stage where the genome was bound to host protein, probably a multimeric protein complex, derived from the ''sinc'' gene. Recalling
Enrico Fermi
Enrico Fermi (; 29 September 1901 – 28 November 1954) was an Italian (later naturalized American) physicist and the creator of the world's first nuclear reactor, the Chicago Pile-1. He has been called the "architect of the nuclear age" and ...
's word play on a neutron-like particle, Outram coined the term 'virino' to describe a small virus. In the virino model, the host protein protects the scrapie agent nucleic acids from degradation and prevents the host from raising an
immune response
An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
, since the protein/nucleic acid complex is seen as a legitimate part of the host. However, the presumed scrapie-associated nucleic acid has not been identified, and physical or chemical evidence for its presence is lacking.
References
{{Reflist
Obsolete scientific theories