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
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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 infectious viral particle production in cells and the lack of cytopathic effects, which are typically useful for screening. To address these issues, we developed a method to efficiently produce vesicular stomatitis virus (VSV) pseudotyped with glycoprotein (G) of members 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 methionine at BoDV-1–G residue 307 increases 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.
期刊介绍:
Microbiology and Immunology is published in association with Japanese Society for Bacteriology, Japanese Society for Virology, and Japanese Society for Host Defense Research. It is peer-reviewed publication that provides insight into the study of microbes and the host immune, biological and physiological responses.
Fields covered by Microbiology and Immunology include:Bacteriology|Virology|Immunology|pathogenic infections in human, animals and plants|pathogenicity and virulence factors such as microbial toxins and cell-surface components|factors involved in host defense, inflammation, development of vaccines|antimicrobial agents and drug resistance of microbes|genomics and proteomics.