Borna disease virus

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Mammalian 1 orthobornavirus
Virus classification Red Pencil Icon.png
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Negarnaviricota
Class: Monjiviricetes
Order: Mononegavirales
Family: Bornaviridae
Genus: Orthobornavirus
Species:
Mammalian 1 orthobornavirus
Borna disease virus 1 G protein
Identifiers
SymbolBDV_G
Pfam PF06208
InterPro IPR009344
Borna disease virus 1 P10 protein
Identifiers
SymbolBDV_P10
Pfam PF06515
InterPro IPR009485
Borna disease virus 1 P40 protein
PDB 1n93 EBI.jpg
crystal structure of the borna disease virus 1 nucleoprotein
Identifiers
SymbolBDV_P40
Pfam PF06407
InterPro IPR009441
SCOP2 1n93 / SCOPe / SUPFAM
Borna disease virus 1 P24 protein
Identifiers
SymbolBDV_P24
Pfam PF06595
InterPro IPR009517

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

Contents

Virology

Genome

BoDV-1/2 have the smallest genome (8.9 kilobases) of any Mononegavirales member and are unique within that order in their ability to replicate within the host cell nucleus.

BoDV-1 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 Mononegavirales .

Several of the proteins encoded by the BoDV-1 genome have been characterised. The G glycoprotein is important for viral entry into the host cell. [1] [2]

It has been suggested that the p10, or X, protein plays a role in viral RNA synthesis or ribonucleoprotein transport. [3]

The P40 nucleoprotein from BoDV-1 is multi-helical in structure and can be divided into two subdomains, each of which has an alpha-bundle topology. [4] 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. [5] Horse and human P24 have no species-specific amino acid residues, suggesting that the two viruses are related. [6] [7] 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. [8] BoDV-1 p24 RNA has been detected in the peripheral blood mononuclear cells (PBMCs) of psychiatric patients with such conditions. [7] Some studies find a significant difference in the prevalence of BDV p24 RNA in patients with mood disorders and schizophrenia, [9] whilst others find no difference between patients and control groups. [7] Consequently, debate about the role of BDV in psychiatric diseases remains alive.

Replication

Bornaviruses enter host cells by endocytosis. The viral genome and associated viral proteins is released into the cytoplasm following fusion of the viral envelope and the endosome membrane. [10] Replication of bornaviruses occurs inside the nucleus. These are the only animal viruses within the order Mononegavirales to do this. Many plant rhabdoviruses replicate in the nucleus.

Bornaviruses have negative sense RNA genomes [11] 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.

Endogenous provirus

Endogenous viral elements 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. [12]

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. [13] The ancestral virus seems likely to have been a high AT content virus.

History

Borna disease was first described in 1885 as "heated head disease" of cavalry horses in 1885 in the town of Borna, Germany. [14]

Related Research Articles

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Paramyxoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates serve as natural hosts. Diseases associated with this family include measles, mumps, and respiratory tract infections. The family has four subfamilies, 17 genera, and 78 species, three genera of which are unassigned to a subfamily.

<i>Filoviridae</i> Family of viruses in the order Mononegavirales

Filoviridae is a family of single-stranded negative-sense RNA viruses in the order Mononegavirales. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in the form of viral hemorrhagic fevers.

<i>Henipavirus</i> Genus of RNA viruses

Henipavirus is a genus of negative-strand RNA viruses in the family Paramyxoviridae, order Mononegavirales containing six established species, and numerous others still under study. Henipaviruses are naturally harboured by several species of small mammals, notably pteropid fruit bats, microbats of several species, and shrews. Henipaviruses are characterised by long genomes and a wide host range. Their recent emergence as zoonotic pathogens capable of causing illness and death in domestic animals and humans is a cause of concern.

<i>Morbillivirus</i> Genus of viruses

Morbillivirus is a genus of viruses in the order Mononegavirales, in the family Paramyxoviridae. Humans, dogs, cats, cattle, seals, and cetaceans serve as natural hosts. This genus includes seven species. Diseases in humans associated with viruses classified in this genus include measles; in animals, they include acute febrile respiratory tract infection.

<i>Rhabdoviridae</i> Family of viruses in the order Mononegavirales

Rhabdoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates, invertebrates, plants, fungi and protozoans serve as natural hosts. Diseases associated with member viruses include rabies encephalitis caused by the rabies virus, and flu-like symptoms in humans caused by vesiculoviruses. The name is derived from Ancient Greek rhabdos, meaning rod, referring to the shape of the viral particles. The family has 40 genera, most assigned to three subfamilies.

<i>Mononegavirales</i> Order of viruses

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 these viruses cause significant disease in humans. Many other important pathogens of nonhuman animals and plants are also in the group. The order includes eleven virus families: Artoviridae, Bornaviridae, Filoviridae, Lispiviridae, Mymonaviridae, Nyamiviridae, Paramyxoviridae, Pneumoviridae, Rhabdoviridae, Sunviridae, and Xinmoviridae.

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, and members of the Bornaviridae family within the Mononegavirales order.

<i>Bornaviridae</i> Family of viruses

Bornaviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Horses, sheep, cattle, rodents, birds, reptiles, and humans serve as natural hosts. Diseases associated with bornaviruses include Borna disease, a fatal neurologic disease of mammals restricted to central Europe; and proventricular dilatation disease (PDD) in birds. Bornaviruses may cause encephalitis in mammals like horses or sheep. The family includes 11 species assigned to three genera.

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Nucleoprotein Type of protein

Nucleoproteins are proteins conjugated with nucleic acids. Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins.

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RNA-dependent RNA polymerase Enzyme that synthesizes RNA from an RNA template

RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to typical DNA-dependent RNA polymerases, which all organisms use to catalyze the transcription of RNA from a DNA template.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

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References

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  2. Perez M, Watanabe M, Whitt MA, de la Torre JC (August 2001). "N-terminal domain of Borna disease virus G (p56) protein is sufficient for virus receptor recognition and cell entry". Journal of Virology. 75 (15): 7078–85. doi:10.1128/JVI.75.15.7078-7085.2001. PMC   114436 . PMID   11435588.
  3. Wolff T, Pfleger R, Wehner T, Reinhardt J, Richt JA (April 2000). "A short leucine-rich sequence in the Borna disease virus p10 protein mediates association with the viral phospho- and nucleoproteins". The Journal of General Virology. 81 (Pt 4): 939–47. doi: 10.1099/0022-1317-81-4-939 . PMID   10725419.
  4. Planz O, Stitz L (February 1999). "Borna disease virus nucleoprotein (p40) is a major target for CD8(+)-T-cell-mediated immune response". Journal of Virology. 73 (2): 1715–8. doi:10.1128/JVI.73.2.1715-1718.1999. PMC   104005 . PMID   9882386.
  5. Zhang G, Kobayashi T, Kamitani W, Komoto S, Yamashita M, Baba S, Yanai H, Ikuta K, Tomonaga K (November 2003). "Borna disease virus phosphoprotein represses p53-mediated transcriptional activity by interference with HMGB1". Journal of Virology. 77 (22): 12243–51. doi:10.1128/jvi.77.22.12243-12251.2003. PMC   254253 . PMID   14581561.
  6. Kishi M, Arimura Y, Ikuta K, Shoya Y, Lai PK, Kakinuma M (January 1996). "Sequence variability of Borna disease virus open reading frame II found in human peripheral blood mononuclear cells". Journal of Virology. 70 (1): 635–40. doi:10.1128/JVI.70.1.635-640.1996. PMC   189858 . PMID   8523585.
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  8. Nunes SO, Itano EN, Amarante MK, Reiche EM, Miranda HC, de Oliveira CE, Matsuo T, Vargas HO, Watanabe MA (2008). "RNA from Borna disease virus in patients with schizophrenia, schizoaffective patients, and in their biological relatives". Journal of Clinical Laboratory Analysis. 22 (4): 314–20. doi:10.1002/jcla.20261. PMC   6649126 . PMID   18623121.
  9. Miranda HC, Nunes SO, Calvo ES, Suzart S, Itano EN, Watanabe MA (January 2006). "Detection of Borna disease virus p24 RNA in peripheral blood cells from Brazilian mood and psychotic disorder patients". Journal of Affective Disorders. 90 (1): 43–7. doi:10.1016/j.jad.2005.10.008. PMID   16324750.
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  14. "Evolutionary Surprise: Eight Percent of Human Genetic Material Comes from a Virus". ScienceDaily. 2010-01-08.