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Viruses Aug 2015The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative... (Review)
Review
The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative antiviral therapy. Moreover, HCV has become a role model to study fundamental principles that govern the replication cycle of a positive strand RNA virus. In fact, for most HCV proteins high-resolution X-ray and NMR (Nuclear Magnetic Resonance)-based structures have been established and profound insights into their biochemical and biological properties have been gained. One example is p7, a small hydrophobic protein that is dispensable for RNA replication, but crucial for the production and release of infectious HCV particles from infected cells. Owing to its ability to insert into membranes and assemble into homo-oligomeric complexes that function as minimalistic ion channels, HCV p7 is a member of the viroporin family. This review compiles the most recent findings related to the structure and dual pore/ion channel activity of p7 of different HCV genotypes. The alternative conformations and topologies proposed for HCV p7 in its monomeric and oligomeric state are described and discussed in detail. We also summarize the different roles p7 might play in the HCV replication cycle and highlight both the ion channel/pore-like function and the additional roles of p7 unrelated to its channel activity. Finally, we discuss possibilities to utilize viroporin inhibitors for antagonizing p7 ion channel/pore-like activity.
Topics: Hepacivirus; Humans; Models, Molecular; Protein Conformation; Viral Proteins; Virus Assembly; Virus Release
PubMed: 26258788
DOI: 10.3390/v7082826 -
Annual Review of Biophysics May 2023The recent proliferation of cryo-electron tomography (cryo-ET) techniques has led to the cryo-ET resolution revolution. Meanwhile, significant efforts have been made to... (Review)
Review
The recent proliferation of cryo-electron tomography (cryo-ET) techniques has led to the cryo-ET resolution revolution. Meanwhile, significant efforts have been made to improve the identification of targets in the cellular context and the throughput of cryo-focused ion beam (FIB) milling. Together, these developments led to a surge of in situ discoveries on how enveloped viruses are assembled and how viruses interact with cells in infected hosts. In this article, we review the recent advances in cryo-ET, high-resolution insights into virus assembly, and the findings from inside infected eukaryotic and prokaryotic cells.
Topics: Electron Microscope Tomography; Virus Assembly
PubMed: 36719970
DOI: 10.1146/annurev-biophys-092022-100958 -
Journal of Molecular Biology Dec 2023Bacteriophages of Borrelia burgdorferi are a biologically important but under-investigated feature of the Lyme disease-causing spirochete. No virulent borrelial viruses...
Bacteriophages of Borrelia burgdorferi are a biologically important but under-investigated feature of the Lyme disease-causing spirochete. No virulent borrelial viruses have been identified, but all B. burgdorferi isolates carry a prophage φBB1 as resident circular plasmids. Like its host, the φBB1 phage is quite distinctive and shares little sequence similarity with other known bacteriophages. We expressed φBB1 head morphogenesis proteins in Escherichia coli which resulted in assembly of homogeneous prolate procapsid structures and used cryo-electron microscopy to determine the three-dimensional structure of these particles. The φBB1 procapsids consist of 415 copies of the major capsid protein and an equal combined number of three homologous capsid decoration proteins that form trimeric knobs on the outside of the particle. One of the end vertices of the particle is occupied by a portal assembled from twelve copies of the portal protein. The φBB1 scaffolding protein is entirely α-helical and has an elongated shape with a small globular domain in the middle. Within the tubular section of the procapsid, the internal scaffold is built of stacked rings, each composed of 32 scaffolding protein molecules, which run in opposite directions from both caps with a heterogeneous part in the middle. Inside the portal-containing cap, the scaffold is organized asymmetrically with ten scaffolding protein molecules bound to the portal. The φBB1 procapsid structure provides better insight into the vast structural diversity of bacteriophages and presents clues of how elongated bacteriophage particles might be assembled.
Topics: Bacteriophages; Borrelia; Capsid; Capsid Proteins; Cryoelectron Microscopy; Virus Assembly
PubMed: 37866476
DOI: 10.1016/j.jmb.2023.168323 -
Current Issues in Molecular Biology 2021Herpesviruses virions are large and complex structures that deliver their genetic content to nuclei upon entering cells. This property is not unusual as many other... (Review)
Review
Herpesviruses virions are large and complex structures that deliver their genetic content to nuclei upon entering cells. This property is not unusual as many other viruses including the adenoviruses, orthomyxoviruses, papillomaviruses, polyomaviruses, and retroviruses, do likewise. However, the means by which viruses in the subfamily accomplish this fundamental stage of the infectious cycle is tied to their defining ability to efficiently invade the nervous system. Fusion of the viral envelope with a cell membrane results in the deposition of the capsid, along with an assortment of tegument proteins, into the cytosol. Establishment of infection requires that the capsid traverse the cytosol, dock at a nuclear pore, and inject its genome into the nucleoplasm. Accumulating evidence indicates that the capsid is not the effector of this delivery process, but is instead shepherded by tegument proteins that remain capsid bound. At the same time, tegument proteins that are released from the capsid upon entry act to increase the susceptibility of the cell to the ensuing infection. Mucosal epithelial cells and neurons are both susceptible to alphaherpesvirus infection and, together, provide the niche to which these viruses have adapted. Although much has been revealed about the functions of expressed tegument proteins during the late stages of assembly and egress, this review will specifically address the roles of tegument proteins brought into the cell with the incoming virion, and our current understanding of alphaherpesvirus genome delivery to nuclei.
Topics: Alphaherpesvirinae; Animals; Capsid Proteins; Cell Nucleus; Cytoplasm; Genome, Viral; Herpesviridae Infections; Humans; Virion; Virus Assembly; Virus Internalization
PubMed: 32807747
DOI: 10.21775/cimb.041.171 -
Physical Biology May 2017Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need... (Review)
Review
Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.
Topics: Models, Biological; Systems Biology; Virus Assembly
PubMed: 28535149
DOI: 10.1088/1478-3975/aa6cdc -
Tumour Virus Research Jun 2023The tegument is the structure between the envelope and nucleocapsid of herpesvirus particles. Viral (and cellular) proteins accumulate to create the layers of the... (Review)
Review
The tegument is the structure between the envelope and nucleocapsid of herpesvirus particles. Viral (and cellular) proteins accumulate to create the layers of the tegument. Some Epstein-Barr virus (EBV) tegument proteins are conserved widely in Herpesviridae, but others are shared only by members of the gamma-herpesvirus subfamily. As the interface to envelope and nucleocapsid, the tegument functions in virion morphogenesis and budding of the nucleocapsid during progeny production. When a virus particle enters a cell, enzymes such as kinase and deubiquitinase, and transcriptional activators are released from the virion to promote virus infection. Moreover, some EBV tegument proteins are involved in oncogenesis. Here, we summarize the roles of EBV tegument proteins, in comparison to those of other herpesviruses.
Topics: Humans; Herpesvirus 4, Human; Virus Assembly; Epstein-Barr Virus Infections; Herpesviridae; Carcinogenesis; Cell Transformation, Neoplastic
PubMed: 37169175
DOI: 10.1016/j.tvr.2023.200260 -
Nucleic Acids Research Oct 2022Liquid-liquid phase separation (LLPS) has assumed a prominent role in biological cell systems, where it underpins the formation of subcellular compartments necessary for...
Liquid-liquid phase separation (LLPS) has assumed a prominent role in biological cell systems, where it underpins the formation of subcellular compartments necessary for cell function. We investigated the underlying mechanism of LLPS in virus infected cells, where virus inclusion bodies are formed by an RNA-binding phosphoprotein (NS2) of Bluetongue virus to serve as sites for subviral particle assembly and virus maturation. We show that NS2 undergoes LLPS that is dependent on protein phosphorylation and RNA-binding and that LLPS occurrence is accompanied by a change in protein secondary structure. Site-directed mutagenesis identified two critical arginine residues in NS2 responsible for specific RNA binding and thus for NS2-RNA complex driven LLPS. Reverse genetics identified the same residues as essential for VIB assembly in infected cells and virus viability. Our findings suggest that a specific arginine-RNA interaction in the context of a phosphorylated state drives LLPS in this, and possibly other, virus infections.
Topics: Animals; Phosphorylation; Virus Assembly; Bluetongue virus; RNA; Arginine
PubMed: 36259663
DOI: 10.1093/nar/gkac904 -
Viruses Oct 2020The 11th International Retroviral Nucleocapsid and Assembly Symposium was held August 15-17, 2019, on the campus of Northeastern University [...].
The 11th International Retroviral Nucleocapsid and Assembly Symposium was held August 15-17, 2019, on the campus of Northeastern University [...].
Topics: Congresses as Topic; Humans; Nucleocapsid; Retroviridae; Virion; Virus Assembly
PubMed: 33142691
DOI: 10.3390/v12111243 -
PLoS Pathogens Apr 2017
Review
Topics: Genes, Viral; RNA, Viral; Rotavirus; Virus Assembly; Virus Replication
PubMed: 28426777
DOI: 10.1371/journal.ppat.1006242 -
Viruses Jun 2021The proper assembly and dissemination of progeny virions is a fundamental step in virus replication. As a whole, viruses have evolved a myriad of strategies to exploit... (Review)
Review
The proper assembly and dissemination of progeny virions is a fundamental step in virus replication. As a whole, viruses have evolved a myriad of strategies to exploit cellular compartments and mechanisms to ensure a successful round of infection. For enveloped viruses such as retroviruses and herpesviruses, acquisition and incorporation of cellular membrane is an essential process during the formation of infectious viral particles. To do this, these viruses have evolved to hijack the host Endosomal Sorting Complexes Required for Transport (ESCRT-I, -II, and -III) to coordinate the sculpting of cellular membrane at virus assembly and dissemination sites, in seemingly different, yet fundamentally similar ways. For instance, at the plasma membrane, ESCRT-I recruitment is essential for HIV-1 assembly and budding, while it is dispensable for the release of HSV-1. Further, HSV-1 was shown to recruit ESCRT-III for nuclear particle assembly and egress, a process not used by retroviruses during replication. Although the cooption of ESCRTs occurs in two separate subcellular compartments and at two distinct steps for these viral lifecycles, the role fulfilled by ESCRTs at these sites appears to be conserved. This review discusses recent findings that shed some light on the potential parallels between retroviral budding and nuclear egress and proposes a model where HSV-1 nuclear egress may occur through an ESCRT-dependent mechanism.
Topics: DNA Viruses; Endosomal Sorting Complexes Required for Transport; HIV-1; Host Microbial Interactions; Humans; Protein Transport; Retroviridae; Virion; Virus Assembly; Virus Release; Virus Replication
PubMed: 34199191
DOI: 10.3390/v13061138