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Bornavirus

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Title: Bornavirus


1
Bornavirus
  • David L. Dowell
  • MCB5505
  • 04/14/04

2
Bornavirus
  • Order Mononegavirales
  • Family Bornaviridae
  • Single Genus Bornavirus
  • Borna Disease Virus (BDV) TS
  • Identified in 1926

3
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

4
Genome
  • Negative sense, single strand RNA
  • Linear, single segment
  • 8.9 kb long
  • Contains at least 6 open reading frames

5
  • 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?

6
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

7
Vectors
  • Origin 1894 Borna, a village in Leipzig
  • An illness of horses
  • Mostly mammals, but also ostriches
  • Humans can self-infect

8
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

9
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

10
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

11
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

12
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

13
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

14
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

15
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

16
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

17
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

18
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

19
  • ANY QUESTIONS???
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