Bornavirus
Encyclopedia
Borna disease virus is the virus that causes Borna disease
.
(8.9 kilobases) of any Mononegavirales species and is unique within that order in its ability to replicate within the host cell nucleus
.
Borna virus was isolated from a diseased horse in the 1970s, but the virus particles were difficult to characterise. Nonetheless, the virus' genome
has been characterised. It is a linear negative-sense single stranded RNA virus
in the order of the mononegavirales
. This order contains the family of lyssavirus
es which includes the viruses responsible for rabies
. A new family named the bornaviridae was created to hold this virus.
Several of the proteins encoded by the Borna virus genome have been characterised.
The G glycoprotein is important for viral entry
into the host cell
.
It has been suggested that the p10, or X, protein plays a role in viral
RNA synthesis or ribonucleoprotein
transport
.
The P40 nucleoprotein from BDV is multi-helical in structure
and can be divided into two subdomains, each of which has an alpha-bundle topology. The nucleoprotein assembles into a planar homotetramer, with the RNA genome either wrapping around the outside of the tetramer
or possibly fitting within the charged central channel of the tetramer .
P24 (phosphoprotein 24) is an essential component of the RNA polymerase
transcription
and replication complex
. P24 is encoded by open reading frame
II (ORF-II) and undergoes high rates of mutation
in humans. It [binds amphoterin-HMGB1, a multifunctional protein, directly and may cause deleterious effects in cellular functions by interference with HMGB1. Horse
and human
P24 have no species-specific amino acid
residues, suggesting that the two viruses are related. Numerous interactions of the immune system
with the central nervous system
have been described. Mood and psychotic disorders, such as severe depression and schizophrenia, are both heterogeneous disorders regarding clinical symptomatology, the acuity of symptoms, the clinical course and the treatment response. BDV p24 RNA has been detected in the peripheral blood mononuclear cells (PBMCs) of psychiatric patient
s with such conditions. Some studies find a significant difference in the prevalence of BDV p24 RNA in patients with mood disorders and schizophrenia
, whilst others find no difference between patients and control groups. Consequently, debate about the role of BDV in psychiatric disease
s remains alive.
. After this virus
has entered its host it is taken up by endosomes. Replication
of the bornavirus occurs inside the nucleus
. This is the only animal virus
within the order Mononegavirales
to do this. Many plant Rhabdoviruses
replicate in the nucleus.
Bornaviruses have negative sense RNA
genomes The negative sense RNA
is copied to make a positive sense RNA template. This template is then used to synthesise
many copies of the negative sense RNA genome
. This is like making copies of a mold, and then using these molds to make many more viruses.
, Germany.
Borna disease
Borna disease is an infectious neurological syndrome of warm-blooded animals, caused by Borna disease virus, which causes abnormal behaviour and fatality....
.
Genome
It has the smallest genomeGenome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
(8.9 kilobases) of any Mononegavirales species and is unique within that order in its ability to replicate within the host cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
.
Borna virus was isolated from a diseased horse in the 1970s, but the virus particles were difficult to characterise. Nonetheless, the virus' genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
has been characterised. It is a linear negative-sense single stranded RNA virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
in the order of the mononegavirales
Mononegavirales
The order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...
. This order contains the family of lyssavirus
Lyssavirus
Lyssavirus is a genus of viruses belonging to the family Rhabdoviridae, in the order Mononegavirales. This group of RNA viruses includes the Rabies virus traditionally associated with the disease.-Structure:Viruses typically have either helical or cubic symmetry...
es which includes the viruses responsible for rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...
. A new family named the bornaviridae was created to hold this virus.
Several of the proteins encoded by the Borna virus genome have been characterised.
The G glycoprotein is important for viral entry
Viral entry
Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variation among viruses, the generalities are quite similar...
into the host cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
.
It has been suggested that the p10, or X, protein plays a role in viral
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
RNA synthesis or ribonucleoprotein
Ribonucleoprotein
Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
transport
Transport
Transport or transportation is the movement of people, cattle, animals and goods from one location to another. Modes of transport include air, rail, road, water, cable, pipeline, and space. The field can be divided into infrastructure, vehicles, and operations...
.
The P40 nucleoprotein from BDV is multi-helical in structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
and can be divided into two subdomains, each of which has an alpha-bundle topology. The nucleoprotein assembles into a planar homotetramer, with the RNA genome either wrapping around the outside of the tetramer
Tetramer
A tetramer is a protein with four subunits . There are homotetramers such as glutathione S-transferase or single-strand binding protein, dimers of hetero-dimers such as hemoglobin , and heterotetramers, where each subunit is different.-Subunit interactions in tetramers:The interactions between...
or possibly fitting within the charged central channel of the tetramer .
P24 (phosphoprotein 24) is an essential component of the RNA polymerase
Polymerase
A polymerase is an enzyme whose central function is associated with polymers of nucleic acids such as RNA and DNA.The primary function of a polymerase is the polymerization of new DNA or RNA against an existing DNA or RNA template in the processes of replication and transcription...
transcription
Transcription
Transcription may refer to:*Transcription , a business which converts speech into a written or electronic text document*Transcription , software which helps convert speech into text transcript...
and replication complex
Protein complex
A multiprotein complex is a group of two or more associated polypeptide chains. If the different polypeptide chains contain different protein domain, the resulting multiprotein complex can have multiple catalytic functions...
. P24 is encoded by open reading frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
II (ORF-II) and undergoes high rates of mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
in humans. It [binds amphoterin-HMGB1, a multifunctional protein, directly and may cause deleterious effects in cellular functions by interference with HMGB1. Horse
Horse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
and human
Human
Humans are the only living species in the Homo genus...
P24 have no species-specific amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
residues, suggesting that the two viruses are related. Numerous interactions of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
with the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
have been described. Mood and psychotic disorders, such as severe depression and schizophrenia, are both heterogeneous disorders regarding clinical symptomatology, the acuity of symptoms, the clinical course and the treatment response. BDV p24 RNA has been detected in the peripheral blood mononuclear cells (PBMCs) of psychiatric patient
Patient
A patient is any recipient of healthcare services. The patient is most often ill or injured and in need of treatment by a physician, advanced practice registered nurse, veterinarian, or other health care provider....
s with such conditions. Some studies find a significant difference in the prevalence of BDV p24 RNA in patients with mood disorders and schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, whilst others find no difference between patients and control groups. Consequently, debate about the role of BDV in psychiatric disease
Mental illness
A mental disorder or mental illness is a psychological or behavioral pattern generally associated with subjective distress or disability that occurs in an individual, and which is not a part of normal development or culture. Such a disorder may consist of a combination of affective, behavioural,...
s remains alive.
Replication
Bornaviruses enter the host by endocytosisEndocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
. After this virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
has entered its host it is taken up by endosomes. Replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
of the bornavirus occurs inside the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
. This is the only animal virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
within the order Mononegavirales
Mononegavirales
The order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...
to do this. Many plant Rhabdoviruses
Rhabdoviridae
Rhabdoviruses are viruses belonging to the family Rhabdoviridae, which is in the order Mononegavirales. The name is derived from the Greek rhabdos meaning rod referring to the shape of the viral particles. Rhabdoviruses infect a broad range of hosts throughout the animal and plant kingdoms...
replicate in the nucleus.
Bornaviruses have negative sense RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
genomes The negative sense RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
is copied to make a positive sense RNA template. This template is then used to synthesise
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
many copies of the negative sense RNA genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
. This is like making copies of a mold, and then using these molds to make many more viruses.
Endogenous provirus
Elements homologous to the nucleoprotein gene of the Bornavirus have been shown to exist in the genomes of several mammalian species.History
The Bornavirus was first described in 1885 as "heated head disease" of cavalry horses in 1885 in the town BornaBorna
Borna is a town in the Free State of Saxony, Germany, capital of the Leipzig district. It is situated approx. 30 km southeast of Leipzig. It has approx. 21,000 inhabitants.-History:Borna as a town is more than 750 years old....
, Germany.