The Borna disease viruses 1 and 2 (BoDV-1 and BoDV-2) are members of the species ''Mammalian 1 orthobornavirus'' and cause

Borna disease Borna disease, also known as sad horse disease, is an infectious neurological syndrome of warm-blooded animals, caused by Borna disease viruses 1 and 2 (BoDV-1/2). BoDV-1/2 are neurotropic viruses of the species ''Mammalian 1 orthobornavirus,'' ...

in mammals.

Virology

Genome

BoDV-1/2 have the smallest

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 ...

(8.9 kilobases) of any ''Mononegavirales'' member and are unique within that order in their ability to replicate within the host

cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...

. BoDV-1 was isolated from a diseased horse in the 1970s, but the virus particles were difficult to characterise. Nonetheless, the virus'

has been characterised. It is a linear negative-sense single stranded RNA

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 ...

in the order ''

Mononegavirales ''Mononegavirales'' is an order of negative-strand RNA viruses which have nonsegmented genomes. Some common members of the order are Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of ...

''. Several of the proteins encoded by the BoDV-1 genome have been characterised. The G glycoprotein is important for

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 (biology), cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Desp ...

into the host

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

. It has been suggested that the p10, or X, protein plays a role in viral RNA synthesis or

ribonucleoprotein Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating in ...

transport Transport (in British English), or transportation (in American English), is the intentional movement of humans, animals, and goods from one location to another. Modes of transport include air, land (rail and road), water, cable, pipeline, an ...

. The P40 nucleoprotein from BoDV-1 is multi-helical in

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

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 A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti ...

or possibly fitting within the charged central channel of the

. P24 (phosphoprotein 24) is an essential component of the RNA

polymerase A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base- ...

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

and replication

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

. P24 is encoded by

open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...

II (ORF-II) and undergoes high rates of

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

s. It inds 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 The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

with the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

have been described. Mood and psychotic disorders, such as severe depression and schizophrenia, are both

heterogeneous Homogeneity and heterogeneity are concepts often used in the sciences and statistics relating to the uniformity of a substance or organism. A material or image that is homogeneous is uniform in composition or character (i.e. color, shape, siz ...

disorders regarding clinical symptomatology, the acuity of symptoms, the clinical course and the treatment response. BoDV-1 p24 RNA has been detected in the

peripheral blood mononuclear cell A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus. These cells consist of lymphocytes (T cells, B cells, NK cells) and monocytes, whereas erythrocytes and platelets have no nuclei, and granulocytes ( ...

s (PBMCs) of psychiatric

patient A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other health c ...

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 is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

, whilst others find no difference between patients and control groups. Consequently, debate about the role of BDV in

psychiatric disease A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...

s remains alive.

Replication

Bornaviruses enter host cells by

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...

. The viral genome and associated viral proteins is released into the cytoplasm following fusion of the viral envelope and the

endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...

membrane. Replication of bornaviruses occurs inside the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

. These are the only animal

es within the order ''

'' to do this. Many plant rhabdoviruses replicate in the nucleus. Bornaviruses have negative sense

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 ...

genomes 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 gen ...

The negative sense

is copied to make a positive sense RNA template. This template is then used to synthesise many copies of the negative sense RNA

. This is like making copies of a mold, and then using these molds to make many more viruses.

Endogenous provirus

Endogenous viral element An endogenous viral element (EVE) is a DNA sequence derived from a virus, and present within the germline of a non-viral organism. EVEs may be entire viral genomes (proviruses), or fragments of viral genomes. They arise when a viral DNA sequence b ...

s homologous to the nucleoprotein gene of BoDV-1 have been shown to exist in the genomes of several mammalian species, including humans and non-human primates.

Evolution

A Bayesian analysis of Borna disease virus 1 suggests that the current strains diversified ~300 years ago and that avian-host bornaviruses evolved considerably earlier than this. The ancestral virus seems likely to have been a high AT content virus.

History

was first described in 1885 as "heated head disease" of cavalry horses in 1885 in the town of Borna, Germany.

References

External links

ViralZone: Bornavirus
* * * * {{Taxonbar, from=Q20721592 Bornaviruses