Selection and characterization of a reovirus mutant with improved thermostability
| Autor: | Anthony J. Snyder, Pranav Danthi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Protease medicine.medical_treatment 030302 biochemistry & molecular biology Mutant Genome Cell biology 03 medical and health sciences chemistry.chemical_compound chemistry Capsid Viral envelope medicine Sodium dodecyl sulfate Function (biology) 030304 developmental biology Thermostability |
| DOI: | 10.1101/511352 |
| Popis: | The environment represents a significant barrier to infection. Physical stressors (heat) or chemical agents (ethanol and sodium dodecyl sulfate) can render virions noninfectious. As such, discrete proteins are necessary to stabilize the dual layered structure of mammalian orthoreovirus (reovirus). The outer capsid participates in cell entry: (i) σ3 is degraded to generate the infectious subviral particle and (ii) μ1 facilitates membrane penetration and subsequent core delivery. μ1-σ3 interactions also prevent inactivation; however, this activity is not fully characterized. Using forward and reverse genetic approaches, we identified two mutations (μ1 M258I and σ3 S344P) within heat resistant strains. σ3 S344P was sufficient to enhance capsid integrity and to reduce protease sensitivity. Moreover, these changes impaired replicative fitness in a reassortant background. This work reveals new details regarding the determinants of reovirus stability.SIGNIFICANCENonenveloped viruses rely on protein-protein interactions to shield their genomes from the environment. The capsid, or protective shell, must also disassemble during cell entry. In this work, we identified a determinant within mammalian orthoreovirus that regulates heat resistance, disassembly kinetics, and replicative fitness. Together, capsid function is balanced for optimal replication and for spread to a new host. |
| Databáze: | OpenAIRE |
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