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J. Virol. doi:10.1128/JVI.02426-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Cell-to-cell spread of Borna disease virus proceeds in the absence of the virus primary receptor and furin mediated processing of the virus surface glycoprotein

Department of Molecular Integrative Neuroscience, The Scripps Research Institute, La Jolla, California 92037

^* To whom correspondence should be addressed. Email: juanct{at}scripps.edu.

	Abstract

Borna disease virus (BDV) is an enveloped virus with a non-segmented negative-strand (NNS) RNA genome whose organization is characteristic of Mononegavirales. BDV cell entry follows a receptor mediated endocytosis pathway, which is initiated by the recognition of an as yet unidentified receptor at the cell surface by the virus glycoprotein (G). BDV G is synthesized as precursor (GPC) that is cleaved by the cellular protease furin to produce the mature glycoproteins GP1 and GP2, which have been implicated in receptor recognition and pH-dependent fusion events, respectively. BDV is highly neurotropic and its spread in cultured cells proceeds in the absence of detectable extra-cellular virus or syncytia formation. BDV spread has been proposed to be strictly dependent on the expression and correct processing of BDV G. Here we present evidence that cell-to-cell spread of BDV required neither expression of cellular receptors involved in virus primary infection, nor furin-mediated processing of BDV G. We also show that in furin deficient cells the release of BDV particles induced by treatment of BDV-infected cells with hypertonic buffer was not significantly affected, while virion infectivity was dramatically impaired correlating with decreased incorporation of BDV G species into viral particles. These findings support the view that propagation of BDV within the CNS of infected hosts involves both a primary infection that follows a receptor mediated endocytosis pathway, and a subsequent cell-to-cell spread that is independent of the expression of the primary receptor and does not require processing of BDV G into GP1 and GP2.