Ins and Outs of Reovirus: Vesicular Trafficking in Viral Entry and Egress

Abstract

Cell entry and egress are essential steps in the viral life cycle that govern pathogenesis and spread. Mammalian orthoreoviruses (reoviruses) are nonenveloped viruses implicated in human disease that serve as tractable models for studies of pathogen–host interactions. In this review we discuss the function of intracellular vesicular transport systems in reovirus entry, trafficking, and egress and comment on shared themes for diverse viruses. Designing strategic therapeutic interventions that impede these steps in viral replication requires a detailed understanding of mechanisms by which viruses coopt vesicular trafficking. We illuminate such targets, which may foster development of antiviral agents.

Captivating Perplexities of Spinareovirinae 5′ RNA Caps

“…The replication of reovirus occurs within localized areas called factories, which are composed of both viral proteins (μ2, μNS, and σNS) and host materials (endoplasmic reticulum (ER) fragments, microtubules, and possibly more) [15]. Ultimately, whole progeny viruses are assembled that can egress from cells, predominantly in a non-lytic manner [9]. (1) Receptor-mediated attachment of complete virions via σ1 to junctional adhesion molecule A (JAM-A) and/or sialic acid (SA) residues on the mammalian cell surface; (2) Following membrane attachment, virions enter the cell via clathrinmediated endocytosis; (3) Endosomal acid-dependent proteases digest the MRV outercapsid, generating ISVPs before the eventual release of core particles into the cytoplasm; (4) Now-transcriptionally active core particles produce mRNAs (initial replication) using the viral λ3 polymerase; (5) After being secreted through the λ2 channels, mRNAs are translated into proteins.…”

“…Replication Cycle. We will provide a brief overview of the replication cycle for MRV here, as illustrated in Figure 3 ; however, readers are directed to a recently published review [ 9 ] for a more in-depth description. Infection begins with entry of the virus into host cells, a process mediated by the attachment of the σ1 receptor binding protein to sialic acids (SAs) and/or junctional adhesion molecule A (JAM-A) residues [ 10 ].…”

“…The replication of reovirus occurs within localized areas called factories, which are composed of both viral proteins (μ2, μNS, and σNS) and host materials (endoplasmic reticulum (ER) fragments, microtubules, and possibly more) [ 15 ]. Ultimately, whole progeny viruses are assembled that can egress from cells, predominantly in a non-lytic manner [ 9 ].…”

Control of Capsid Transformations during Reovirus Entry

“…The initial entry events of reovirus, including attachment and internalization pathways, have been extensively reviewed elsewhere and will not be covered in great detail in this review [ 5 , 6 ]. In brief, attachment to host cells is mediated by the viral σ1 protein.…”

The human neuronal receptor NgR1 bridges reovirus capsid proteins to initiate infection

“…Mammalian orthoreoviruses (reoviruses) provide a highly tractable and well-established experimental system to study mechanisms of viral receptor engagement and how receptor use influences disease. Reovirus virions are nonenveloped, double-shelled particles that undergo stepwise binding to host cells and proteolytic disassembly prior to releasing a transcriptionally active viral core unit to the cell cytosol [1]. Reovirus causes age-restricted disease in many mammalian species [2–4] and readily infects humans [5–8].…”