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/bornavirus1.html • Bornavirus; http://www.stanford.edu/group/virus/1999/monical/bornavirus.html • The nervous system; http://www.emc.maricopa.edu/faculty/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???