Bornavirus David L. Dowell MCB5505 04/14/04

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

Structure Spherical envelope Crescent-like inner core Nucleocapsid 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

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

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?

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

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

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

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

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

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

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

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

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

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

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

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

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

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