Bornavirus

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Bornavirus

• David L. Dowell
• MCB5505
• 04/14/04

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Bornavirus

• Order Mononegavirales
• Family Bornaviridae
• Single Genus Bornavirus
• Borna Disease Virus (BDV) TS
• Identified in 1926

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Structure

• Spherical envelope
• 90-130 nm diameter
• Two types of glycoprotein spikes, GP43 and GP84
• Crescent-like inner core
• Nucleocapsid
• 60 nm diameter
• 4 nm width
• Contains a helical Ribonucleo protein complex

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Genome

• Negative sense, single strand RNA
• Linear, single segment
• 8.9 kb long
• Contains at least 6 open reading frames

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• N nucleoprotein (p40)
• P phosphoprotein (p24)
• M matrix protein (gp18)
• G envelope protein (gp94)
• L RNA-dependent RNA polymerase (p190)
• X unknown function (p10) - nuclear import
  function for other virus-encoded proteins?

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Genome

• Negative sense, single strand RNA
• Linear, single segment
• 8.9 kb long
• Contains at least 6 open reading frames
• Similarities in nucleotide sequence and ORF
  structure suggest close relation to Rhabdoviridae
  

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Vectors

• Origin 1894 Borna, a village in Leipzig
• An illness of horses
• Mostly mammals, but also ostriches
• Humans can self-infect

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Replication

• Endocytosis
• Viral GP84 (also GP18) protein probably used for
  adsorption with unknown cellular receptor
• GP43 involved in pH-dependent fusion after
  internalization
• Taken up by endosomes

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Replication (continued)

• Only known member of order Mononegavirales to
  replicate in nucleus
• Both () and (-) sense RNA in nucleus
• () sense localized in nucleolus
• (-) sense (genomic) in both nucleolar and
  non-nucleolar regions
• Subgenomic RNAs modified post-transcriptionally
  by RNA splicing
• Specific details on replication and splicing
  mechanisms are still unknown

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General Summary

• Order Mononegavirales
• Enveloped, (-) sense, single strand, linear,
  single segmented RNA
• Similar to Rhabdoviridae in nucleotide sequence
  and ORF structure
• Mammals, birds, humans can self-infect
• Replicates in nucleus

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Host Range

• Wide host range mammals to birds
• Likely includes all warm-blooded animals
• Natural reservoir unknown
• Rodents proposed, but no evidence of natural
  infection so theory remains speculative

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Transmission

• Intranasal infection shown by early inflammation
  of olfactory bulbs of infected horses
• Infection also by contact with bodily secretions
  and excretions containing BDV RNA
• Blood-borne transmission with BDV RNA and protein
  in peripheral blood
• All proposed theories routes have yet to be
  fully proved

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Pathogenesis

• Noncytolytic, neurotropic
• virus
• Causes Borna disease in horses
• and sheep
• Severe, frequently fatal neuro-
• logical disease
• Progressive, nonpurulent encephalomyelitis
• sad horse disease
• Usually asymptomatic, BDV antibodies found in
  clinically healthy horses
• When present, symptoms include behavioral
  changes, hyperactivity and disturbances in gait
  early in infection, and ataxia and partial
  paralysis during terminal stages

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Neuropathogenesis

• BDV migrates intraaxonally
• towards CNS after early intra-
• neuronal replication
• Preferential tropism for limbic system, including
  hippocampus
• Regulation of memory, behavior and emotions
• Significant in human psychiatric disorders
• Later infection can spread through peripheral
  nervous system and non-neural organs and tissues
  if sustained

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Neuropathogenesis (continued)

• Experimental infection results in inflammatory
  reaction in the brain
• Can cause neuronal degeneration
• Caudate nucleus, dentate gyrus, and hippocampus
• Speculation BDV is a zoonotic illness infecting
  individuals occupationally exposed to animals
• Received attention in the press who suggested BDV
  infection possibly linked to rural suicide and
  depression
• BDV-linked psychopathology is controversial and
  significant substantiated proof is yet to be
  discovered

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Neuropathogenesis (Therapy)

• Amantadine and ribavirin both successfully used
  against bornavirus
• Amantadine is a glutamate receptor antagonist may
  have antidepressant effects
• Still unclear as to whether this is
• due to its antiviral activity or
• neurotransmitter system
• modulation

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Cool Summary

• Host Range ostriches to horses to Indiana Jones
• Transmission routes nasal cavity,
  secretion/excretion contact, blood theoretical
• Borna disease in animals
• Neurological disease can cause encephalomyelitis,
  usually asymptomatic, but can cause behavioral
  changes/psychological effects
• Virus progresses CNS, PNS, extra-nervous
• Speculation of BDV as zoonotic illness, but
  unsubstantiated
• Amantadine/ribavirin possible treatment
• Antidepressant effects (amantadine) controversial
  stem

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References

• Bornavirus Microbiology Immunology
  http//www-micro.msb.le.ac.uk/3035/Bornavirus.html
  
• Bornavirus www.vu-wien.ac.at/i123/spezvir/bornavi
  rus1.html
• Bornavirus http//www.stanford.edu/group/virus/19
  99/monical/bornavirus.html
• The nervous system http//www.emc.maricopa.edu/fa
  culty/farabee/BIOBK/BioBookNERV.html
• Bornavirus www.rki.de/PRESSE/PD_THEMA/BORNA.HTM
• Limbic System The Center of Emotions
  http//www.epub.org.br/cm/n05/mente/limbic_i.htm

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• ANY QUESTIONS???