Surface glycoprotein of Borna disease virus mediates virus spread from cell to cell.
Borna disease virus (BDV) is a non-segmented negative-stranded RNA virus that maintains a strictly neurotropic and persistent infection in affected end hosts. The primary target cells for BDV infection are brain cells, e.g. neurons and astrocytes. The exact mechanism of how infection is propagated between these cells and especially the role of the viral glycoprotein (GP) for cell-cell transmission, however, are still incompletely understood. Here, we use different cell culture systems, including rat primary astrocytes and mixed cultures of rat brain cells, to show that BDV primarily spreads through cell-cell contacts. We employ a highly stable and efficient peptidomimetic inhibitor to inhibit the furin-mediated processing of GP and demonstrate that cleaved and fusion-active GP is strictly necessary for the cell-to-cell spread of BDV. Together, our quantitative observations clarify the role of Borna disease virus-glycoprotein for viral dissemination and highlight the regulation of GP expression as a potential mechanism to limit viral spread and maintain persistence. These findings furthermore indicate that targeting host cell proteases might be a promising approach to inhibit viral GP activation and spread of infection.
Institute of Virology, Philipps University Marburg, Marburg, Germany.|Department of Biochemistry, University of Oxford, Oxford, UK.
Frank
F
Lennartz
Institute of Virology, Philipps University Marburg, Marburg, Germany.
Karen
K
Bayer
Institute of Veterinary Pathology, Justus-Liebig-University Giessen, Giessen, Germany.
Nadine
N
Czerwonka
Institute of Virology, Philipps University Marburg, Marburg, Germany.
Yinghui
Y
Lu
Institute of Veterinary Pathology, Justus-Liebig-University Giessen, Giessen, Germany.
Kristine
K
Kehr
Institute of Veterinary Pathology, Justus-Liebig-University Giessen, Giessen, Germany.
Manuela
M
Hirz
Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marburg, Germany.
Torsten
T
Steinmetzer
Institute of Virology, Philipps University Marburg, Marburg, Germany.
Wolfgang
W
Garten
Institute of Veterinary Pathology, Justus-Liebig-University Giessen, Giessen, Germany.
Christiane
C
Herden
D000818:Animals; D001253:Astrocytes / Q000821:virology; D001550:Benzamidines / Q000494:pharmacology; D001891:Borna disease virus / Q000378:metabolism / Q000472:pathogenicity*; D001921:Brain / Q000166:cytology / Q000821:virology; D002459:Cell Fusion; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004285:Dogs; D045683:Furin / Q000037:antagonists & inhibitors; D054884:Host-Pathogen Interactions / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells / Q000821:virology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D011917:Rats, Inbred Lew; D014709:Vero Cells / Q000821:virology
D001550:Benzamidines; C000611989:MI-0701; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D045683:Furin
cleavage of virus glycoprotein; furin inhibitor; fusion-mediated virus infection