Packaging of Genomic RNA in Positive-Sense Single-Stranded RNA Viruses: A Complex Story.

Mauricio Comas-Garcia

doi:10.3390/v11030253

Mauricio Comas-Garcia

Open Access

https://doi.org/10.3390/v11030253

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Journal: Viruses	Publication Date: Mar 13, 2019
Citations: 229	License type: CC BY 4.0

Affiliation: Autonomous University of San Luis Potosí

Abstract

The packaging of genomic RNA in positive-sense single-stranded RNA viruses is a key part of the viral infectious cycle, yet this step is not fully understood. Unlike double-stranded DNA and RNA viruses, this process is coupled with nucleocapsid assembly. The specificity of RNA packaging depends on multiple factors: (i) one or more packaging signals, (ii) RNA replication, (iii) translation, (iv) viral factories, and (v) the physical properties of the RNA. The relative contribution of each of these factors to packaging specificity is different for every virus. In vitro and in vivo data show that there are different packaging mechanisms that control selective packaging of the genomic RNA during nucleocapsid assembly. The goals of this article are to explain some of the key experiments that support the contribution of these factors to packaging selectivity and to draw a general scenario that could help us move towards a better understanding of this step of the viral infectious cycle.

Highlights

Nucleocapsid assembly and the RNA replication of positive-sense single-stranded RNA [(+)ssRNA] viruses occur in the cytoplasm
By using single-molecule fluorescence correlation spectroscopy (sm-FCS) they were able to work under extremely diluted capsid protein (CP) and RNA concentrations, thereby minimizing non-specific protein-RNA interactions that could drive non-selective packaging of satellite tobacco necrotic virus (STNV), HBV and MS2 viral RNAs
The genomic RNA (gRNA) of (+)ssRNA viruses is like a Swiss Army knife in that (i) it contains the minimal genetic information required for the infectious cycle, (ii) is the template for RNA replication, (iii) is a messenger RNA, (iv) can act as a scaffold during virion assembly, and (v) has to be able to present different RNA structures to regulate these processes during the infectious cycle

Summary

Introduction

Nucleocapsid assembly and the RNA replication of positive-sense single-stranded RNA [(+)ssRNA] viruses occur in the cytoplasm. While sometimes criticized as reductionist and/or biologically irrelevant, in vitro approaches have been crucial to the understanding of the physical principles that control the assembly of empty virions and nucleocapsids, as well as RNA packaging [5,6,7,8,11,12,31,34,35,36,37,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84] These experiments have demonstrated that: (i) the assembly of (+)ssRNA viruses requires protein-protein and RNA-protein interactions, (ii) this process is spontaneous, and (iii) virion assembly and RNA packaging are coupled with each other. Chaturvedi, S. et al showed that the role of BMV RdRp on RNA packaging selectivity is not due to gRNA compartmentalization, but to a direct interaction between the RdRp and the CP [38]

Packaging Signals

Replication and Translation Contribute to Packaging Specificity

Membrane Re-Arrangement and Viral Factories

Findings

Conclusions