Membrane architects: how positive-strand RNA viruses restructure the cell

Abstract

Virus infection is a process that requires combined contributions from both virus and host factors. For this process to be efficient within the crowded host environment, viruses have evolved ways to manipulate and reorganize host structures to produce cellular microenvironments. Positive-strand RNA virus replication and assembly occurs in association with cytoplasmic membranes, causing a reorganization of these membranes to create microenvironments that support viral processes. Similarities between virus-induced membrane domains and cellular organelles have led to the description of these structures as virus replication organelles (vRO). Electron microscopy analysis of vROs in positive-strand RNA virus infected cells has revealed surprising morphological similarities between genetically diverse virus species. For all positive-strand RNA viruses, vROs can be categorized into two groups: those that make invaginations into the cellular membranes (In-vRO), and those that cause the production of protrusions from cellular membranes (Pr-vRO), most often in the form of double membrane vesicles (DMVs). In this review, we will discuss the current knowledge on the structure and biogenesis of these two different vRO classes as well as comparing morphology and function of vROs between various positive-strand RNA viruses. Finally, we will discuss recent studies describing pharmaceutical intervention in vRO formation as an avenue to control virus infection.

Inhibition of PIKFYVE kinase interferes ESCRT pathway to suppress RNA virus replication

“…In further subcellular fractions and electron microscopy analyses, YM201636 decreased the distribution of viral replication complex in endolysosome vesicles and electron‐dense structures with stacked membrane, which are shaped as VPs containing several inner vesicles with a large outer membrane and are considered to be the sites of viral replication of RNA viruses of Picornaviridae , Flaviviridae , and Togaviridae families 40 . In positive‐strand RNA viruses, the assembly of viruses is a highly organized, complex process close proximity to the DMVs, with spatiotemporal distribution dynamics of viral proteins and RNA in infected cells 41 . In fact, viral RNA synthesis is not restricted to DMVs in cells upon picornaviruses infection 42 .…”

“…40 In positivestrand RNA viruses, the assembly of viruses is a highly organized, complex process close proximity to the DMVs, with spatiotemporal distribution dynamics of viral proteins and RNA in infected cells. 41 In fact, viral RNA synthesis is not restricted to DMVs in cells upon picornaviruses infection. 42 that PIKFYVE acts as a perspective drug target against Ebola virus 43 and SARS-CoV-2.…”

The Host Cytoskeleton Functions as a Pleiotropic Scaffold: Orchestrating Regulation of the Viral Life Cycle and Mediating Host Antiviral Innate Immune Responses

“…During the replication of a positive-stranded RNA virus, viral replication organelles (vROs) composed of bilayer membrane-like structures are formed. The viral genomic RNA is wrapped in vROs to avoid the genome being degraded by other substances in the cytoplasm [ 87 ]. Live-cell imaging and sensors are used to monitor viral infections and replication, which shows that perinuclear inclusion in the SARS-CoV-2-infected cells is positive for dsRNA.…”

Actomyosin‐driven motility and coalescence of phase‐separated viral inclusion bodies are required for efficient replication of a plant rhabdovirus

“…As obligate intracellular parasites, viruses exploit cellular functions and processes to build their replication compartments. While positive‐strand RNA viruses typically form replication factories on remodeled membranous organelles (Laliberte & Zheng, 2014; Neufeldt & Cortese, 2022; Nishikiori et al ., 2022), nonsegmented negative‐strand RNA viruses (NNSVs, order Mononegavirales ) during replication induce the formation of membraneless organelles, commonly known as viroplasms, viral factories, or viral inclusion bodies (IBs; Dolnik et al ., 2021; Wu et al ., 2022). These electron‐dense IBs contain viral RNAs and nucleocapsid core proteins essential for replication, that is, the nucleoprotein (N or NP), phosphoprotein (P), and the large RNA‐dependent RNA polymerase (L) in the case of rhabdoviruses, paramyxoviruses, and filoviruses.…”