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Generation and Assembly of Virus-Specific Nucleocapsids of the Respiratory Syncytial Virus
Published on: July 27, 2021
A Cool Look at Positive-Strand RNA Virus Replication Organelles: New Insights from Cryo-Electron Microscopy
Nina L de Beijer1, Eric J Snijder1, Montserrat Bárcena2
1Molecular Virology Laboratory, Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Abstract:
Positive-strand RNA viruses encompass a variety of established and emerging eukaryotic pathogens. Their genome replication is confined to specialized cytoplasmic membrane compartments known as replication organelles (ROs). These ROs derive from host membranes, transformed into distinct structures such as invaginated spherules or intricate membrane networks including single- and/or double-membrane vesicles. ROs play a vital role in orchestrating viral RNA synthesis and evading detection by innate immune sensors of the host. In recent years, groundbreaking cryo-electron microscopy studies conducted with several prototypic viruses have significantly advanced our understanding of RO structure and function. Notably, these studies unveiled the presence of crown-shaped multimeric viral protein complexes that seem to actively participate in viral RNA synthesis and regulate the release of newly synthesized RNA into the cytosol for translation and packaging. These findings have shed light on novel viral functions and fascinating macromolecular complexes that delineate promising new avenues for future research.
Insights
Replication organelles (ROs) are crucial for positive-strand RNA virus replication and immune evasion. Recent cryo-electron microscopy reveals novel viral protein complexes within ROs, essential for RNA synthesis and release.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Positive-strand RNA viruses utilize specialized cytoplasmic membrane compartments called replication organelles (ROs) for genome replication.
- ROs are derived from host membranes and adopt diverse structures, including spherules and membrane networks.
- These organelles are critical for viral RNA synthesis and for evading host innate immune responses.
Purpose of the Study:
- To elucidate the structure and function of replication organelles (ROs) in positive-strand RNA virus replication.
- To investigate the role of novel viral protein complexes within ROs.
- To understand how ROs facilitate viral RNA synthesis and immune evasion.
Main Methods:
- Cryo-electron microscopy (cryo-EM) of prototypic positive-strand RNA viruses.
- Structural analysis of viral protein complexes within replication organelles.
- Functional studies on viral RNA synthesis and host immune evasion.
Main Results:
- Cryo-EM studies revealed crown-shaped multimeric viral protein complexes within ROs.
- These complexes appear to actively engage in viral RNA synthesis.
- The complexes regulate the release of newly synthesized RNA for translation and packaging.
Conclusions:
- Novel viral protein complexes are key players in positive-strand RNA virus replication.
- Replication organelles are sophisticated structures essential for viral propagation and immune evasion.
- These findings open new research avenues for antiviral strategies targeting viral macromolecular complexes.
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