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Real-Time Imaging of Polioviral RNA Translocation across a Membrane. | LitMetric

Real-Time Imaging of Polioviral RNA Translocation across a Membrane.

mBio

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA

Published: February 2021

AI Article Synopsis

  • Genome transfer from viruses into host cells is essential for viral replication, with enveloped viruses using membrane fusion, while nonenveloped viruses like poliovirus have unclear mechanisms.
  • A new single-particle fluorescence assay was developed to study genome release in poliovirus, revealing a complex process with multiple steps that can be enhanced by wild-type capsid protein VP4.
  • This research provides key insights into how poliovirus efficiently releases its genome and introduces a method that can be used to explore genome release in other nonenveloped viruses, potentially uncovering new therapeutic targets.

Article Abstract

Genome transfer from a virus into a cell is a critical early step in viral replication. Enveloped viruses achieve the delivery of their genomes into the cytoplasm by merging the viral membrane with the cellular membrane via a conceptually simple mechanism called membrane fusion. In contrast, genome translocation mechanisms in nonenveloped viruses, which lack viral membranes, remain poorly understood. Although cellular assays provide useful information about cell entry and genome release, it is difficult to obtain detailed mechanistic insights due both to the inherent technical difficulties associated with direct visualization of these processes and to the prevalence of nonproductive events in cellular assays performed at a very high multiplicity of infection. To overcome these issues, we developed an single-particle fluorescence assay to characterize genome release from a nonenveloped virus (poliovirus) in real time using a tethered receptor-decorated liposome system. Our results suggest that poliovirus genome release is a complex process that consists of multiple rate-limiting steps. Interestingly, we found that the addition of exogenous wild-type capsid protein VP4, but not mutant VP4, enhanced the efficiency of genome translocation. These results, together with prior structural analysis, suggest that VP4 interacts with RNA directly and forms a protective, membrane-spanning channel during genome translocation. Furthermore, our data indicate that VP4 dynamically interacts with RNA, rather than forming a static tube for RNA translocation. This study provides new insights into poliovirus genome translocation and offers a cell-free assay that can be utilized broadly to investigate genome release processes in other nonenveloped viruses. The initial transfer of genomic material from a virus into a host cell is a key step in any viral infection. Consequently, understanding how viruses deliver their genomes into cells could reveal attractive therapeutic targets. Although conventional biochemical and cellular assays have provided useful information about cell entry, the mechanism used to deliver the viral genomes across the cellular membrane into the cytoplasm is not well characterized for nonenveloped viruses such as poliovirus. In this study, we developed a fluorescence imaging assay to visualize poliovirus genome release using a synthetic vesicle system. Our results not only provide new mechanistic insights into poliovirus genome translocation but also offer a cell-free assay to bridge gaps in understanding of this process in other nonenveloped viruses.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545138PMC
http://dx.doi.org/10.1128/mBio.03695-20DOI Listing

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