Control of Capsid Transformations during Reovirus Entry.

Stephanie L Gummersheimer,Anthony J Snyder,Pranav Danthi

doi:10.3390/v13020153

Abstract

Mammalian orthoreovirus (reovirus), a dsRNA virus with a multilayered capsid, serves as a model system for studying the entry of similar viruses. The outermost layer of this capsid undergoes processing to generate a metastable intermediate. The metastable particle undergoes further remodeling to generate an entry-capable form that delivers the genome-containing inner capsid, or core, into the cytoplasm. In this review, we highlight capsid proteins and the intricacies of their interactions that control the stability of the capsid and consequently impact capsid structural changes that are prerequisites for entry. We also discuss a novel proviral role of host membranes in promoting capsid conformational transitions. Current knowledge gaps in the field that are ripe for future investigation are also outlined.

Highlights

Among related dsRNA viruses with multilayered capsids that are well studied, the triggers for conformational changes in the outer capsid that precede cell membrane penetration appear distinct from those used by reovirus
This work further connects assembly of the virus to infectious subvirion particle (ISVP)* formation and suggests that the metastability of the reovirus outer capsid is affected by core proteins that are thought to remain static during cell entry
We discussed the roles of various capsid proteins during reovirus entry

Summary

Introduction

Viruses have evolved numerous methods of exploiting the host cell machinery to initiate uptake and release of the viral genome to begin replication. Studies of these mechanisms have revealed insights into cellular transport machinery, endosomal characteristics, viral structural components and sorting mechanisms. The entry process must, contain an added layer of complexity in which only the outer layer of the particle is lost during the disassembly steps prior to endosomal escape and the entire core is delivered to the host cell cytoplasm. We will summarize new data that suggest unexpected roles for additional viral capsid proteins in controlling the metastability of the particle that impact the kinetics and efficiency of cell entry

Structural Changes Required for Membrane Penetration Are Controlled by the μ1

Target Membranes Control Structural Transitions in the Virus Particle

Role for σ1 and λ2

Role for σ2 and λ1

Conclusions