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 Crescent-like inner core Nucleocapsid
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;
Bornavirus;
Bornavirus;
The nervous system;
Bornavirus;
Limbic System: The Center of Emotions

19. ANY QUESTIONS???