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.
Borna disease virus (BDV) is an enveloped virus with a nonsegmented negative-strand 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 a 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 extracellular virus or syncytium 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 the expression of cellular receptors involved in virus primary infection, nor the furin-mediated processing of BDV G. We also show that in furin-deficient cells, the release of BDV particles induced by the treatment of BDV-infected cells with hypertonic buffer was not significantly affected, while virion infectivity was dramatically impaired, correlating with the decreased incorporation of BDV G species into viral particles. These findings support the view that the propagation of BDV within the central nervous systems 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 the processing of BDV G into GP1 and GP2.
Clemente
Roberto
R
Department of Molecular Integrative Neuroscience, The Scripps Research Institute, IMM6, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
de la Torre
Juan C
JC
D000818:Animals; D001891:Borna disease virus / Q000472:pathogenicity*; D016466:CHO Cells; D036022:Capsid Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D006224:Cricetinae; D003412:Cricetulus; D045683:Furin / Q000172:deficiency* / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D011991:Receptors, Virus / Q000172:deficiency* / Q000502:physiology; D014709:Vero Cells
D036022:Capsid Proteins; D006023:Glycoproteins; D011991:Receptors, Virus; D045683:Furin