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Nature Reviews. Microbiology Aug 2015Major advances have occurred in recent years in our understanding of HIV-1 assembly, release and maturation, as work in this field has been propelled forwards by... (Review)
Review
Major advances have occurred in recent years in our understanding of HIV-1 assembly, release and maturation, as work in this field has been propelled forwards by developments in imaging technology, structural biology, and cell and molecular biology. This increase in basic knowledge is being applied to the development of novel inhibitors designed to target various aspects of virus assembly and maturation. This Review highlights recent progress in elucidating the late stages of the HIV-1 replication cycle and the related interplay between virology, cell and molecular biology, and drug discovery.
Topics: Gene Expression Regulation, Viral; HIV-1; Humans; Viral Proteins; Virus Assembly; Virus Release; Virus Replication
PubMed: 26119571
DOI: 10.1038/nrmicro3490 -
Trends in Microbiology Jan 2011Assembly of virus capsids and surface proteins must be regulated to ensure that the resulting complex is an infectious virion. In this review, we examine assembly of... (Review)
Review
Assembly of virus capsids and surface proteins must be regulated to ensure that the resulting complex is an infectious virion. In this review, we examine assembly of virus capsids, focusing on hepatitis B virus and bacteriophage MS2, and formation of glycoproteins in the alphaviruses. These systems are structurally and biochemically well-characterized and are simplest-case paradigms of self-assembly. Published data suggest that capsid and glycoprotein assembly is subject to allosteric regulation, that is regulation at the level of conformational change. The hypothesis that allostery is a common theme in viruses suggests that deregulation of capsid and glycoprotein assembly by small molecule effectors will be an attractive antiviral strategy, as has been demonstrated with hepatitis B virus.
Topics: Allosteric Regulation; Antiviral Agents; Capsid Proteins; Glycoproteins; Virus Assembly; Viruses
PubMed: 21163649
DOI: 10.1016/j.tim.2010.11.003 -
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 -
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 -
ACS Nano Apr 2020Understanding viral assembly pathways is of critical importance to biology, medicine, and nanotechology. Here, we study the assembly path of a system with various...
Understanding viral assembly pathways is of critical importance to biology, medicine, and nanotechology. Here, we study the assembly path of a system with various structures, the simian vacuolating virus 40 (SV40) polymorphs. We simulate the templated assembly process of VP1 pentamers, which are the constituents of SV40, into icosahedal shells made of = 12 pentamers ( = 1). The simulations include connections formed between pentamers by C-terminal flexible lateral units, termed here "C-terminal ligands", which are shown to control assembly behavior and shell dynamics. The model also incorporates electrostatic attractions between the N-terminal peptide strands (ligands) and the negatively charged cargo, allowing for agreement with experiments of RNA templated assembly at various pH and ionic conditions. During viral assembly, pentamers bound to any template increase its effective size due to the length and flexibility of the C-terminal ligands, which can connect to other VP1 pentamers and recruit them to a partially completed capsid. All closed shells formed other than the = 1 feature the ability to dynamically rearrange and are thus termed "pseudo-closed". The = 13 shell can even spontaneously "self-correct" by losing a pentamer and become a = 1 capsid when the template size fluctuates. Bound pentamers recruiting additional pentamers to dynamically rearranging capsids allow closed shells to continue growing the pseudo-closed growth mechanism, for which experimental evidence already exists. Overall, we show that the C-terminal ligands control the dynamic assembly paths of SV40 polymorphs.
Topics: Capsid; Capsid Proteins; Simian virus 40; Virus Assembly
PubMed: 32208635
DOI: 10.1021/acsnano.9b10004 -
Journal of Molecular Biology Jul 2011The assembly of an HIV-1 particle is a complex, multistep process involving several viral and cellular proteins, RNAs and lipids. While many macroscopic and fixed-cell... (Review)
Review
The assembly of an HIV-1 particle is a complex, multistep process involving several viral and cellular proteins, RNAs and lipids. While many macroscopic and fixed-cell microscopic techniques have provided important insights into the structure of HIV-1 particles and the mechanisms by which they assemble, analysis of individual particles and their assembly in living cells offers the potential of surmounting many of the limitations inherent in other approaches. In this review, we discuss how the recent application of live-cell microscopic imaging techniques has increased our understanding of the process of HIV-1 particle assembly. In particular, we focus on recent studies that have employed total internal reflection fluorescence microscopy and other single-virion imaging techniques in live cells. These approaches have illuminated the dynamics of Gag protein assembly, viral RNA packaging and ESCRT (endosomal sorting complex required for transport) protein recruitment at the level of individual viral particles. Overall, the particular advantages of individual particle imaging in living cells have yielded findings that would have been difficult or impossible to obtain using macroscopic or fixed-cell microscopic techniques.
Topics: HIV-1; Humans; Imaging, Three-Dimensional; Microscopy; Virion; Virus Assembly
PubMed: 21762796
DOI: 10.1016/j.jmb.2011.04.062 -
ELife Dec 2023Nucleotide and force-dependent mechanisms control how the viral genome of lambda bacteriophage is inserted into capsids.
Nucleotide and force-dependent mechanisms control how the viral genome of lambda bacteriophage is inserted into capsids.
Topics: DNA, Viral; Bacteriophage lambda; Capsid; Genome, Viral; Nucleotides; Virus Assembly
PubMed: 38095555
DOI: 10.7554/eLife.94128 -
TheScientificWorldJournal Mar 2010
Topics: Biophysics; Membrane Fusion; Virus Assembly; Virus Physiological Phenomena
PubMed: 20305984
DOI: 10.1100/tsw.2010.53 -
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 -
Molecular Therapy : the Journal of the... Jan 2010Adeno-associated virus (AAV) vector genomes have been limited to 5 kilobases (kb) in length because their packaging limit was thought to be similar to the size of the...
Adeno-associated virus (AAV) vector genomes have been limited to 5 kilobases (kb) in length because their packaging limit was thought to be similar to the size of the parent AAV genome. Recent reports claim that significantly larger vector genomes can be packaged intact. We examined the packaged vector genomes from plasmid-encoded AAV vectors that ranged from 4.7 to 8.7 kb in length, using AAV types 2, 5, and 8 capsids. Southern blot analysis indicated that packaged AAV vector genomes never exceeded 5.2 kb in length irrespective of the size of the plasmid-encoded vector or the capsid type. This result was confirmed by vector genome probing with strand-specific oligonucleotides. The packaged vector genomes derived from plasmid-encoded vectors exceeding 5 kb were heterogeneous in length and truncated on the 5' end. Despite their truncated genomes, vector preparations produced from plasmid-encoded vectors exceeding 5.2 kb mediated reporter gene expression in vitro at high multiplicity of infection (MOI). The efficiency of expression was substantially lower than that of reporter vectors with genomes <5 kb in length. We propose that transcriptionally functional, intact vector genomes are generated in cells transduced at high MOI from the fragmentary genomes of these larger vectors, probably by recombination.
Topics: Blotting, Southern; Cell Line; Dependovirus; Electrophoresis; Genetic Vectors; Genome, Viral; Humans; Immunoblotting; Virus Assembly
PubMed: 19904234
DOI: 10.1038/mt.2009.255