Leveraging Synthetic Virology for the Rapid Engineering of Vesicular Stomatitis Virus (VSV)

Viruses, Journal Year: 2024, Volume and Issue: 16(10), P. 1641 - 1641

Published: Oct. 21, 2024

Vesicular stomatitis virus (VSV) is a prototype RNA that has been instrumental in advancing our understanding of viral molecular biology and applications vaccine development, cancer therapy, antiviral screening, more. Current VSV genome plasmids for purchase or contract services provide limited options modification, restricted to predefined cloning sites insert locations. Improved methods tools engineer will unlock further insights into long-standing virology questions new opportunities innovative therapies. Here, we report the design construction full-length genome. The 11,161 base pair synthetic (synVSV) was assembled from four modularized DNA fragments. Following rescue titration, phenotypic analysis showed no significant differences between natural viruses. To demonstrate utility platform, then engineered with foreign glycoprotein, common use case studying entry developing anti-virals. show freedom afforded by this modified rearranging gene order, switching positions VSV-P VSV-M genes. This work represents technical advance, providing flexible, cost-efficient platform rapid genomes, facilitating development

Language: Английский

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The Bovine Seminal Plasma Protein PDC-109 Possesses Pan-Antiviral Activity

Viruses, Journal Year: 2022, Volume and Issue: 14(9), P. 2031 - 2031

Published: Sept. 13, 2022

Mammalian seminal plasma contains a multitude of bioactive components, including lipids, glucose, mineral elements, metabolites, proteins, cytokines, and growth factors, with various functions during insemination fertilization. The protein PDC-109 is one the major soluble components bovine ejaculate crucially important for sperm motility, capacitation, acrosome reaction. A hitherto underappreciated function its anti-microbial antiviral activity, which may limit sexual transmission infectious diseases intercourse. We have recently discovered that inhibits membrane fusion activity influenza virus particles significantly impairs viral infections at micromolar concentrations. Here we investigated whether restricted to Influenza or if other mammalian viruses are similarly affected. focused on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), etiological agent Coronavirus Disease 19 (COVID-19), thoroughly assessing inhibition SARS-CoV-2 Spike (S)-pseudotyped reporter particles, but also live-virus infections. Consistent our previous publications, found significant inhibition, albeit accompanied by substantial cytotoxicity. However, using time-of-addition experiments treatment regimen enables suppression without affecting cell viability. furthermore demonstrated able impair mediated VSV glycoprotein (VSVg), thus indicating broad pan-antiviral against multiple species families.

Language: Английский

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The Bovine Seminal Plasma Protein PDC-109 Possesses Pan-Antiviral Activity

Published: July 5, 2022

Mammalian seminal plasma contains a multitude of bioactive components, including lipids, glucose, mineral elements, metabolites, proteins, cytokines and growth factors, with various functions during insemination fertilization. The protein PDC-109 is one the major soluble components bovine ejaculate crucially important for sperm motility, capacitation acrosome reaction. A hitherto underappreciated function its anti-microbial anti-viral activity, which may limit sexual transmission infectious diseases intercourse. We have recently discovered that inhibits membrane fusion activity influenza virus particles significantly impairs viral infections at micromolar concentrations. Here we investigated whether antiviral restricted to Influenza or if other mammalian viruses are similarly affected. focused on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), etiological agent Coronavirus Disease 19 (COVID-19), thoroughly assessing inhibition SARS-CoV-2 Spike (S)-pseudotyped reporter particles, but also live-virus infections. Consistent our previous publications found significant inhibition, albeit accompanied by substantial cytotoxicity. Using time-of-addition experiments however, treatment regimen enable suppression without affecting cell viability. furthermore demonstrated able impair mediated VSV glycoprotein (VSVg) thus indicating broad pan-antiviral against multiple species families.

Language: Английский

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Pseudotyped Viruses for Coronaviruses

Advances in experimental medicine and biology, Journal Year: 2023, Volume and Issue: unknown, P. 133 - 151

Published: Jan. 1, 2023

Language: Английский

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An efficient plasmid-based system for the recovery of recombinant vesicular stomatitis virus encoding foreign glycoproteins

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 16, 2023

Abstract Viral glycoproteins mediate entry into host cells, thereby dictating range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus (VSV) encoding foreign can provide a convenient safe surrogate system to interrogate function, evolution, antigenicity viral from viruses that are difficult manipulate or those requiring high biosafety levels containment. However, production recombinant VSV be technically challenging. this work, we present an efficient robust plasmid-based for glycoproteins. We validate using different families, including arenaviruses, coronaviruses, hantaviruses, as well highlight their utility studying effects mutations on fitness. Overall, methods described herein facilitate study both native serve basis VSV-based vaccines.

Language: Английский

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