Surface glycoprotein of Borna disease virus mediates virus spread from cell to cell

Cellular Microbiology
Frank LennartzC Herden

Abstract

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.

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Citations

Mar 5, 2016·Traffic·Judith M White, Gary R Whittaker
May 24, 2016·Animal Health Research Reviews·Ian TizardSusan Payne
Dec 3, 2016·The Journal of General Virology·Caroline M CharlierCécile E Malnou
Mar 17, 2019·International Journal of Molecular Sciences·Alexandra KupkeChristiane Herden
Mar 2, 2019·Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
Oct 8, 2021·Microbiology and Immunology·Mako YanaiKeizo Tomonaga

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Methods Mentioned

BETA
glycosylation
electrophoresis
FCS

Software Mentioned

BDV
ImageJ
GP

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