Control of Capsid Transformations during Reovirus Entry

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.

Keywords: capsid; cell entry; reovirus.

Figure 1

(A) Cryoelectron microscopy (cryoEM) structure of reovirus virions rendered from PDB 2CSE (A) and its schematic representation (B) are shown. Core proteins, μ1, σ3 and σ1 are shown in green, yellow, blue and black, respectively. σ1 is not resolved in the cryoEM structure. (C) A trimer of μ1 is shown with each monomer in a shade of yellow. (D) Cleavage fragments of the μ1 protein formed during the entry of virus particles into cells are shown.

Figure 2

Reovirus entry schematic. Reovirus virions are internalized following engagement to cell surface receptors and disassemble to form infectious subvirion particles (ISVPs) within the endosomal compartment. ISVPs undergo conformational transitions to form ISVP*s and release μ1 fragments that facilitate membrane penetration. We propose (shown in grey boxes) that a small proportion of μ1 fragments are exposed or released from the particles following ISVP formation. These fragments interact with the host membrane and recruit ISVP-like particles to host membranes and promote their conversion to ISVP*s. Red boxes indicate key virus entry intermediates.