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2003 ; 77
(22
): 12222-31
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Borna disease virus glycoprotein is required for viral dissemination in neurons
#MMPMID14581559
Bajramovic JJ
; Münter S
; Syan S
; Nehrbass U
; Brahic M
; Gonzalez-Dunia D
J Virol
2003[Nov]; 77
(22
): 12222-31
PMID14581559
show ga
Borna disease virus (BDV) is a nonsegmented negative-strand RNA virus with a
tropism for neurons. Infection with BDV causes neurological diseases in a wide
variety of animal species. Although it is known that the virus spreads from
neuron to neuron, assembled viral particles have never been visualized in the
brains of infected animals. This has led to the hypothesis that BDV spreads as
nonenveloped ribonucleoproteins (RNP) rather than as enveloped viral particles.
We assessed whether the viral envelope glycoprotein (GP) is required for neuronal
dissemination of BDV by using primary cultures of rat hippocampal neurons. We
show that upon in vitro infection, BDV replicated and spread efficiently in this
system. Despite rapid virus dissemination, very few infectious viral particles
were detectable in the culture. However, neutralizing antibodies directed against
BDV-GP inhibited BDV spread. In addition, interference with BDV-GP processing by
inhibiting furin-mediated cleavage of the glycoprotein blocked virus spread.
Finally, antisense treatment with peptide nucleic acids directed against BDV-GP
mRNA inhibited BDV dissemination, marking BDV-GP as an attractive target for
antiviral therapy against BDV. Together, our results demonstrate that the
expression and correct processing of BDV-GP are necessary for BDV dissemination
in primary cultures of rat hippocampal neurons, arguing against the hypothesis
that the virus spreads from neuron to neuron in the form of nonenveloped RNP.