A single amino acid substitution in the Borna disease virus glycoprotein enhances the infectivity titer of vesicular stomatitis virus pseudotyped virus by altering membrane fusion activity

Akiba, Y.; Matsugo, H.; Kanda, T.; Sakai, M.; Makino, A.; Tomonaga, K.

doi:10.1101/2024.05.22.595257

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bioRxiv · 10.1101/2024.05.22.595257

A single amino acid substitution in the Borna disease virus glycoprotein enhances the infectivity titer of vesicular stomatitis virus pseudotyped virus by altering membrane fusion activity

Akiba, Y.·Matsugo, H.·Kanda, T.·Sakai, M.·Makino, A.·Tomonaga, K.

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Abstract

Borna disease virus 1 (BoDV-1) causes acute fatal encephalitis in mammals, including humans. Despite its importance, research on BoDV-1 cell entry has been hindered by low viral particle production in cells and the lack of cytopathic effects. To address these issues, we developed a method to efficiently produce vesicular stomatitis virus (VSV) pseudotyped with glycoprotein (G) of the genus Orthobornavirus, including BoDV-1. We discovered that optimal G expression is required to obtain a high infectivity titer of the VSV pseudotyped virus. Remarkably, the infectivity of the VSV pseudotyped virus with G from the BoDV-1 strain huP2br was significantly higher than that of the VSV pseudotyped virus with G from the He/80 strain. Mutational analysis demonstrated that the BoDV-1-G residue 307 determines the infectivity titer of VSV pseudotyped with BoDV-1-G (VSV-BoDV-1-G). A cell-cell fusion assay indicated that this residue plays a pivotal role in membrane fusion, thus suggesting that high membrane fusion activity and a broad pH range for membrane fusion are crucial for achieving a high infectivity titer of VSV-BoDV-1-G. This finding may be extended to increase the infectivity titer of VSV pseudotyped virus with other orthobornavirus G. Our study also contributes to identifying functional domains of BoDV-1-G and provides insight into G-mediated cell entry.

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Akiba, Y., Matsugo, H., Kanda, T., Sakai, M., Makino, A., Tomonaga, K.. 2024-05-22. A single amino acid substitution in the Borna disease virus glycoprotein enhances the infectivity titer of vesicular stomatitis virus pseudotyped virus by altering membrane fusion activity. https://doi.org/10.1101/2024.05.22.595257

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