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Trends in Biochemical Sciences May 2021Virion assembly is an important step in the life cycle of all viruses. For viruses of the Flavivirus genus, a group of enveloped positive-sense RNA viruses, the assembly... (Review)
Review
Virion assembly is an important step in the life cycle of all viruses. For viruses of the Flavivirus genus, a group of enveloped positive-sense RNA viruses, the assembly step represents one of the least understood processes in the viral life cycle. While assembly is primarily driven by the viral structural proteins, recent studies suggest that several nonstructural proteins also play key roles in coordinating the assembly and packaging of the viral genome. This review focuses on describing recent advances in our understanding of flavivirus virion assembly, including the intermolecular interactions between the viral structural (capsid) and nonstructural proteins (NS2A and NS2B-NS3), host factors, as well as features of the viral genomic RNA required for efficient flavivirus virion assembly.
Topics: Flavivirus; RNA, Viral; Viral Nonstructural Proteins; Virion; Virus Assembly
PubMed: 33423940
DOI: 10.1016/j.tibs.2020.12.007 -
Cold Spring Harbor Perspectives in... Nov 2015This work reviews specific related aspects of hepatitis delta virus (HDV) reproduction, including virion structure, the RNA genome, the mode of genome replication, the... (Review)
Review
This work reviews specific related aspects of hepatitis delta virus (HDV) reproduction, including virion structure, the RNA genome, the mode of genome replication, the delta antigens, and the assembly of HDV using the envelope proteins of its helper virus, hepatitis B virus (HBV). These topics are considered with perspectives ranging from a history of discovery through to still-unsolved problems. HDV evolution, virus entry, and associated pathogenic potential and treatment of infections are considered in other articles in this collection.
Topics: Hepatitis D; Hepatitis Delta Virus; Humans; Virus Assembly; Virus Replication
PubMed: 26525452
DOI: 10.1101/cshperspect.a021568 -
Advances in Experimental Medicine and... 2024Poxvirus assembly has been an intriguing area of research for several decades. While advancements in experimental techniques continue to yield fresh insights, many... (Review)
Review
Poxvirus assembly has been an intriguing area of research for several decades. While advancements in experimental techniques continue to yield fresh insights, many questions are still unresolved. Large genome sizes of up to 380 kbp, asymmetrical structure, an exterior lipid bilayer, and a cytoplasmic life cycle are some notable characteristics of these viruses. Inside the particle are two lateral bodies and a protein wall-bound-biconcave core containing the viral nucleocapsid. The assembly progresses through five major stages-endoplasmic reticulum (ER) membrane alteration and rupture, crescent formation, immature virion formation, genome encapsidation, virion maturation and in a subset of viruses, additional envelopment of the virion prior to its dissemination. Several large dsDNA viruses have been shown to follow a comparable sequence of events. In this chapter, we recapitulate our understanding of the poxvirus morphogenesis process while reviewing the most recent advances in the field. We also briefly discuss how virion assembly aids in our knowledge of the evolutionary links between poxviruses and other Nucleocytoplasmic Large DNA Viruses (NCLDVs).
Topics: Poxviridae; Virus Assembly; Humans; Genome, Viral; Virion; Animals; Evolution, Molecular; Endoplasmic Reticulum
PubMed: 38801570
DOI: 10.1007/978-3-031-57165-7_3 -
Current Opinion in Virology Jun 2019The assembly of exact numbers of protein monomers into the distinct architectures of virus capsids has long been of intrigue. Despite the diseases associated with... (Review)
Review
The assembly of exact numbers of protein monomers into the distinct architectures of virus capsids has long been of intrigue. Despite the diseases associated with viruses, there is a paucity of anti-viral therapies; however, mapping virus capsid assembly at the molecular level may lead to the development of more therapeutics. Native mass spectrometry is a powerful, versatile tool with which to monitor biomolecular assembly pathways and identify key intermediates. Recent highlights in this field in terms of MDa mass measurements, identification of capsid intermediates, and the effect of external parameters on assembly are discussed. Examples from ion mobility spectrometry-mass spectrometry, charge detection mass spectrometry, and gas-phase electrophoretic molecular analysis research are presented.
Topics: Capsid Proteins; Mass Spectrometry; Models, Molecular; Virus Assembly; Virus Physiological Phenomena; Viruses
PubMed: 30861488
DOI: 10.1016/j.coviro.2019.02.006 -
Annual Review of Biophysics May 2019Viruses, entities composed of nucleic acids, proteins, and in some cases lipids lack the ability to replicate outside their target cells. Their components self-assemble... (Review)
Review
Viruses, entities composed of nucleic acids, proteins, and in some cases lipids lack the ability to replicate outside their target cells. Their components self-assemble at the nanoscale with exquisite precision-a key to their biological success in infection. Recent advances in structure determination and the development of biophysical tools such as single-molecule spectroscopy and noncovalent mass spectrometry allow unprecedented access to the detailed assembly mechanisms of simple virions. Coupling these techniques with mathematical modeling and bioinformatics has uncovered a previously unsuspected role for genomic RNA in regulating formation of viral capsids, revealing multiple, dispersed RNA sequence/structure motifs [packaging signals (PSs)] that bind cognate coat proteins cooperatively. The PS ensemble controls assembly efficiency and accounts for the packaging specificity seen in vivo. The precise modes of action of the PSs vary between viral families, but this common principle applies across many viral families, including major human pathogens. These insights open up the opportunity to block or repurpose PS function in assembly for both novel antiviral therapy and gene/drug/vaccine applications.
Topics: Animals; Antiviral Agents; Evolution, Molecular; Humans; RNA Viruses; RNA, Viral; Virus Assembly
PubMed: 30951648
DOI: 10.1146/annurev-biophys-052118-115611 -
Viruses Dec 2021Retroviruses have a very complex and tightly controlled life cycle which has been studied intensely for decades. After a virus enters the cell, it reverse-transcribes... (Review)
Review
Retroviruses have a very complex and tightly controlled life cycle which has been studied intensely for decades. After a virus enters the cell, it reverse-transcribes its genome, which is then integrated into the host genome, and subsequently all structural and regulatory proteins are transcribed and translated. The proteins, along with the viral genome, assemble into a new virion, which buds off the host cell and matures into a newly infectious virion. If any one of these steps are faulty, the virus cannot produce infectious viral progeny. Recent advances in structural and molecular techniques have made it possible to better understand this class of viruses, including details about how they regulate and coordinate the different steps of the virus life cycle. In this review we summarize the molecular analysis of the assembly and maturation steps of the life cycle by providing an overview on structural and biochemical studies to understand these processes. We also outline the differences between various retrovirus families with regards to these processes.
Topics: Capsid; Cryoelectron Microscopy; Genome, Viral; HIV-1; Humans; Models, Molecular; Retroviridae; Virion; Virus Assembly
PubMed: 35062258
DOI: 10.3390/v14010054 -
Acta Virologica 2021Nora virus is a RNA picorna-like virus that produces a persistent infection in Drosophila melanogaster. The genome is approximately 12,300 bases and is divided into four...
Nora virus is a RNA picorna-like virus that produces a persistent infection in Drosophila melanogaster. The genome is approximately 12,300 bases and is divided into four open reading frames (ORFs). Structurally, there are four important viral proteins: VP3, VP4A, VP4B, and VP4C. Three proteins (VP4A, VP4B, and VP4C) that form the virion's capsid are encoded by ORF 4, which produces a polyprotein that is post-translationally cleaved. The fourth protein (VP3) is encoded by ORF 3 and it is hypothesized to play a role in virion stability. The genes for these proteins were individually cloned into Escherichia coli, expressed, and the proteins were purified. Virus-like particles (VLPs) were assembled in vitro by mixing the proteins together in different combinations and measured via electron microscopy. Assemblies that contained VP4A and/or VP3 created VLPs with similar sizes to purified empty Nora virus capsids, potentially indicating that VP4A and/or VP3 are vital for Nora virus capsid structure, assembly, and/or stability. Not only does this study provide insight into the role of Nora virus proteins, but it may also lead to a deeper understanding of how Nora virus or other picorna-like viruses undergo assembly. Keywords: RNA viruses; Nora virus; picorna-like virus; virus-like particles; capsid assembly.
Topics: Animals; Capsid; Capsid Proteins; Drosophila melanogaster; Persistent Infection; RNA Viruses; Virion; Virus Assembly
PubMed: 34796712
DOI: 10.4149/av_2021_403 -
Methods in Molecular Biology (Clifton,... 2022The four serotypes of dengue virus (DENV), belonging to the genus Flavivirus in the family Flaviviridae, are the leading cause of arboviral diseases in humans. The...
The four serotypes of dengue virus (DENV), belonging to the genus Flavivirus in the family Flaviviridae, are the leading cause of arboviral diseases in humans. The clinical presentations range from dengue fever to dengue hemorrhagic fever and dengue shock syndrome. Despite decades of efforts on developing intervention strategies against DENV, there is no licensed antiviral, and safe and effective vaccines remain challenging. Similar to other flaviviruses, the assembly of DENV particles occurs in the membranes derived from endoplasmic reticulum; immature virions bud into the lumen followed by maturation in the trans-Golgi and transport through the secretary pathway. A unique feature of flavivirus replication is the production of small and slowly sedimenting subviral particles, known as virus-like particles (VLPs). Co-expression of premembrane (prM) and envelope (E) proteins can generate recombinant VLPs, which are biophysically and antigenically similar to infectious virions and have been employed to study the function of prM and E proteins, assembly, serodiagnostic antigens, and vaccine candidates. Previously, we have developed several assays including sucrose cushion ultracentrifugation, sucrose gradient ultracentrifugation, membrane flotation, subcellular fractionation, and glycosidase digestion assay to exploit the interaction between DENV prM and E proteins, membrane association, subcellular localization, glycosylation pattern, and assembly of VLPs and replicon particles. The information derived from these assays have implications to further our understanding of DENV assembly, replication cycle, intervention strategies, and pathogenesis.
Topics: Antibodies, Viral; Dengue Virus; Humans; Membrane Proteins; Sucrose; Viral Matrix Proteins; Virus Assembly
PubMed: 34709636
DOI: 10.1007/978-1-0716-1879-0_6 -
Viruses Oct 2020One of the most important steps in any viral lifecycle is the production of progeny virions. For retroviruses as well as other viruses, this step is a highly organized... (Review)
Review
One of the most important steps in any viral lifecycle is the production of progeny virions. For retroviruses as well as other viruses, this step is a highly organized process that occurs with exquisite spatial and temporal specificity on the cellular plasma membrane. To facilitate this process, retroviruses encode short peptide motifs, or L domains, that hijack host factors to ensure completion of this critical step. One such cellular machinery targeted by viruses is known as the Endosomal Sorting Complex Required for Transport (ESCRTs). Typically responsible for vesicular trafficking within the cell, ESCRTs are co-opted by the retroviral Gag polyprotein to assist in viral particle assembly and release of infectious virions. This review in the Viruses Special Issue "The 11th International Retroviral Nucleocapsid and Assembly Symposium", details recent findings that shed light on the molecular details of how ESCRTs and the ESCRT adaptor protein ALIX, facilitate retroviral dissemination at sites of viral assembly.
Topics: Endosomal Sorting Complexes Required for Transport; HIV-1; Nucleocapsid; Retroviridae; Ribonucleoproteins; Virus Assembly; Virus Release; gag Gene Products, Human Immunodeficiency Virus
PubMed: 33092109
DOI: 10.3390/v12101188 -
Advances in Anatomy, Embryology, and... 2017All viruses produce infectious particles that possess some degree of stability in the extracellular environment yet disassemble upon cell contact and entry. For the... (Review)
Review
All viruses produce infectious particles that possess some degree of stability in the extracellular environment yet disassemble upon cell contact and entry. For the alphaherpesviruses, which include many neuroinvasive viruses of mammals, these metastable virions consist of an icosahedral capsid surrounded by a protein matrix (referred to as the tegument) and a lipid envelope studded with glycoproteins. Whereas the capsid of these viruses is a rigid structure encasing the DNA genome, the tegument and envelope are dynamic assemblies that orchestrate a sequential series of events that ends with the delivery of the genome into the nucleus. These particles are adapted to infect two different polarized cell types in their hosts: epithelial cells and neurons of the peripheral nervous system. This review considers how the virion is assembled into a primed state and is targeted to infect these cell types such that the incoming particles can subsequently negotiate the diverse environments they encounter on their way from plasma membrane to nucleus and thereby achieve their remarkably robust neuroinvasive infectious cycle.
Topics: Alphaherpesvirinae; Animals; Cell Membrane; Cell Nucleus; Herpesviridae Infections; Humans; Virion; Virus Assembly
PubMed: 28528444
DOI: 10.1007/978-3-319-53168-7_8