Bornavirus David L Dowell MCB 5505 041404 Bornavirus

Bornavirus David L. Dowell MCB 5505 04/14/04

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

Structure n Spherical envelope n n 90 -130 nm diameter Two types of glycoprotein spikes, GP 43 and GP 84 Crescent-like inner core Nucleocapsid n n n 60 nm diameter 4 nm width Contains a helical Ribonucleo protein complex

Genome Negative sense, single strand RNA n Linear, single segment n 8. 9 kb long n Contains at least 6 open reading frames n

• N: nucleoprotein (p 40) • P: phosphoprotein (p 24) • M: matrix protein (gp 18) • G: envelope protein (gp 94) • L: RNA-dependent RNA polymerase (p 190) • X: unknown function (p 10) - nuclear import function for other virusencoded proteins?

Genome Negative sense, single strand RNA n Linear, single segment n 8. 9 kb long n Contains at least 6 open reading frames n Similarities in nucleotide sequence and ORF structure suggest close relation to Rhabdoviridae n

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

Replication n n Endocytosis Viral GP 84 (also GP 18) protein probably used for adsorption with unknown cellular receptor GP 43 involved in p. H-dependent fusion after internalization Taken up by endosomes

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

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

Host Range n Wide host range: mammals to birds Likely includes all warm-blooded animals n Natural reservoir unknown n n 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 n Infection also by contact with bodily secretions and excretions containing BDV RNA n Blood-borne transmission with BDV RNA and protein in peripheral blood n All proposed theories; routes have yet to be fully proved n

Pathogenesis n n Noncytolytic, neurotropic virus Causes Borna disease in horses and sheep n n n Severe, frequently fatal neurological 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 n n BDV migrates intraaxonally towards CNS after early intraneuronal replication Preferential tropism for limbic system, including hippocampus n n n 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) n Experimental infection results in inflammatory reaction in the brain n Speculation BDV is a zoonotic illness infecting individuals occupationally exposed to animals n n Can cause neuronal degeneration Caudate nucleus, dentate gyrus, and hippocampus 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 n Amantadine is a glutamate receptor antagonist may have antidepressant effects n n Still unclear as to whether this is due to its antiviral activity or neurotransmitter system modulation

Cool Summary n n n Host Range: ostriches to horses to Indiana Jones Transmission routes: nasal cavity, secretion/excretion contact, blood; theoretical Borna disease in animals n n 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 n Antidepressant effects (amantadine) controversial stem

References n n n Bornavirus: Microbiology & Immunology; http: //wwwmicro. msb. le. ac. uk/3035/Bornavirus. html Bornavirus; www. vuwien. ac. at/i 123/spezvir/bornavirus 1. html Bornavirus; http: //www. stanford. edu/group/virus/1999/monical/bornavirus. html The nervous system; http: //www. emc. maricopa. edu/faculty/farabee/BIOBK/Bio. Boo k. NERV. html Bornavirus; www. rki. de/PRESSE/PD_THEMA/BORNA. HTM Limbic System: The Center of Emotions http: //www. epub. org. br/cm/n 05/mente/limbic_i. htm

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