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Journal of Dental Research Apr 2009Human papillomaviruses (HPVs) are small dsDNA tumor viruses, which are the etiologic agents of most cervical cancers and are associated with a growing percentage of... (Review)
Review
Human papillomaviruses (HPVs) are small dsDNA tumor viruses, which are the etiologic agents of most cervical cancers and are associated with a growing percentage of oropharyngeal cancers. The HPV capsid is non-enveloped, having a T=7 icosahedral symmetry formed via the interaction among 72 pentamers of the major capsid protein, L1. The minor capsid protein L2 associates with L1 pentamers, although it is not known if each L1 pentamer contains a single L2 protein. The HPV life cycle strictly adheres to the host cell differentiation program, and as such, native HPV virions are only produced in vivo or in organotypic "raft" culture. Research producing synthetic papillomavirus particles--such as virus-like particles (VLPs), papillomavirus-based gene transfer vectors, known as pseudovirions (PsV), and papillomavirus genome-containing quasivirions (QV)--has bypassed the need for stratifying and differentiating host tissue in viral assembly and has allowed for the rapid analysis of HPV infectivity pathways, transmission, immunogenicity, and viral structure.
Topics: Alphapapillomavirus; Humans; Viral Proteins; Virion; Virus Assembly; Virus Replication
PubMed: 19407149
DOI: 10.1177/0022034509333446 -
The International Journal of... Sep 2010The paramyxoviruses define a diverse group of enveloped RNA viruses that includes a number of important human and animal pathogens. Examples include human respiratory... (Review)
Review
The paramyxoviruses define a diverse group of enveloped RNA viruses that includes a number of important human and animal pathogens. Examples include human respiratory syncytial virus and the human parainfluenza viruses, which cause respiratory illnesses in young children and the elderly; measles and mumps viruses, which have caused recent resurgences of disease in developed countries; the zoonotic Hendra and Nipah viruses, which have caused several outbreaks of fatal disease in Australia and Asia; and Newcastle disease virus, which infects chickens and other avian species. Like other enveloped viruses, paramyxoviruses form particles that assemble and bud from cellular membranes, allowing the transmission of infections to new cells and hosts. Here, we review recent advances that have improved our understanding of events involved in paramyxovirus particle formation. Contributions of viral matrix proteins, glycoproteins, nucleocapsid proteins, and accessory proteins to particle formation are discussed, as well as the importance of host factor recruitment for efficient virus budding. Trafficking of viral structural components within infected cells is described, together with mechanisms that allow for the selection of specific sites on cellular membranes for the coalescence of viral proteins in preparation of bud formation and virion release.
Topics: Animals; Humans; Paramyxovirinae; Viral Proteins; Virus Assembly; Virus Release
PubMed: 20398786
DOI: 10.1016/j.biocel.2010.04.005 -
Journal of the American Chemical Society Jan 2019Disruption of virus capsid assembly has compelling antiviral potential that has been applied to hepatitis B virus (HBV). HBV core protein assembly can be modulated by...
Disruption of virus capsid assembly has compelling antiviral potential that has been applied to hepatitis B virus (HBV). HBV core protein assembly can be modulated by heteroaryldihydropyrimidines (HAPs), and such molecules are collectively termed core protein allosteric modulators (CpAMs). Although the antiviral effects of CpAMs are acknowledged, the mechanism of action remains an open question. Challenging aspects of characterizing misdirected assembly are the large size and nonuniform nature of the final particles. In this study of HBV assembly, we observed a competition between normative and CpAM-induced aberrant assembly with electron microscopy and resistive-pulse sensing on nanofluidic devices. This competition was a function of the strength of the association energy between individual core proteins, which is proportional to ionic strength. At strong association energy, assembly reactions primarily yielded morphologically normal HBV capsids, despite the presence of HAP-TAMRA. At weak association energy, HAP-TAMRA led to increased assembly product size and disrupted morphology. The smallest particles were T = 4 icosahedra, whereas the larger particles were defective spheres, ellipsoids, and bacilliform cylinders, with regions of T = 4 geometry interspersed with flat regions. Deviation from spherical geometry progressively increased with particle size, which is consistent with the interpretation of a competition between two alternative assembly pathways.
Topics: Antiviral Agents; Capsid; Hepatitis B virus; Osmolar Concentration; Particle Size; Pyrimidines; Rhodamines; Sodium Chloride; Virus Assembly
PubMed: 30537810
DOI: 10.1021/jacs.8b10131 -
Virology Apr 2014As a member of the retrovirus family, HIV-1 packages its RNA genome into particles and replicates through a DNA intermediate that integrates into the host cellular... (Review)
Review
As a member of the retrovirus family, HIV-1 packages its RNA genome into particles and replicates through a DNA intermediate that integrates into the host cellular genome. The multiple genes encoded by HIV-1 are expressed from the same promoter and their expression is regulated by splicing and ribosomal frameshift. The full-length HIV-1 RNA plays a central role in viral replication as it serves as the genome in the progeny virus and is used as the template for Gag and GagPol translation. In this review, we summarize findings that contribute to our current understanding of how full-length RNA is expressed and transported, cis- and trans-acting elements important for RNA packaging, the locations and timing of RNA:RNA and RNA:Gag interactions, and the processes required for this RNA to be packaged into viral particles.
Topics: HIV-1; RNA, Viral; Virion; Virus Assembly
PubMed: 24530126
DOI: 10.1016/j.virol.2014.01.019 -
Viruses Jan 2022Several strategies have been developed to fight viral infections, not only in humans but also in animals and plants. Some of them are based on the development of... (Review)
Review
Several strategies have been developed to fight viral infections, not only in humans but also in animals and plants. Some of them are based on the development of efficient vaccines, to target the virus by developed antibodies, others focus on finding antiviral compounds with activities that inhibit selected virus replication steps. Currently, there is an increasing number of antiviral drugs on the market; however, some have unpleasant side effects, are toxic to cells, or the viruses quickly develop resistance to them. As the current situation shows, the combination of multiple antiviral strategies or the combination of the use of various compounds within one strategy is very important. The most desirable are combinations of drugs that inhibit different steps in the virus life cycle. This is an important issue especially for RNA viruses, which replicate their genomes using error-prone RNA polymerases and rapidly develop mutants resistant to applied antiviral compounds. Here, we focus on compounds targeting viral structural capsid proteins, thereby inhibiting virus assembly or disassembly, virus binding to cellular receptors, or acting by inhibiting other virus replication mechanisms. This review is an update of existing papers on a similar topic, by focusing on the most recent advances in the rapidly evolving research of compounds targeting capsid proteins of RNA viruses.
Topics: Antiviral Agents; Capsid Proteins; Humans; RNA Virus Infections; RNA Viruses; Virus Assembly; Virus Replication
PubMed: 35215767
DOI: 10.3390/v14020174 -
Physiology (Bethesda, Md.) Aug 2011Assembly and release of human immunodeficiency virus type 1 (HIV-1) particles is mediated by the viral Gag polyprotein precursor. Gag is synthesized in the cytosol and... (Review)
Review
Assembly and release of human immunodeficiency virus type 1 (HIV-1) particles is mediated by the viral Gag polyprotein precursor. Gag is synthesized in the cytosol and rapidly translocates to membrane to orchestrate particle production. The cell biology of HIV-1 Gag trafficking is currently one of the least understood aspects of HIV-1 replication. In this review, we highlight the current understanding of the cellular machinery involved in Gag trafficking and virus assembly.
Topics: HIV-1; Humans; Protein Transport; Virus Assembly; gag Gene Products, Human Immunodeficiency Virus
PubMed: 21841072
DOI: 10.1152/physiol.00051.2010 -
The capsid protein of human immunodeficiency virus: intersubunit interactions during virus assembly.The FEBS Journal Nov 2009The capsid protein (CA) of HIV-1 is composed of two domains, the N-terminal domain (NTD) and the C-terminal domain (CTD). During the assembly of the immature HIV-1... (Review)
Review
The capsid protein (CA) of HIV-1 is composed of two domains, the N-terminal domain (NTD) and the C-terminal domain (CTD). During the assembly of the immature HIV-1 particle, both CA domains constitute a part of the Gag polyprotein, which forms a spherical capsid comprising up to 5000 radially arranged, extended subunits. Gag-Gag interactions in the immature capsid are mediated in large part by interactions between CA domains, which are involved in the formation of a lattice of connected Gag hexamers. After Gag proteolysis during virus maturation, the CA protein is released, and approximately 1000-1500 free CA subunits self-assemble into a truncated cone-shaped capsid. In the mature capsid, NTD-NTD and NTD-CTD interfaces are involved in the formation of CA hexamers, and CTD-CTD interfaces connect neighboring hexamers through homodimerization. The CA-CA interfaces involved in the assembly of the immature capsid and those forming the mature capsid are different, at least in part. CA appears to have evolved an extraordinary conformational plasticity, which allows the creation of multiple CA-CA interfaces and the occurrence of CA conformational switches. This minireview focuses on recent structure-function studies of the diverse CA-CA interactions and interfaces involved in HIV-1 assembly. Those studies are leading to a better understanding of molecular recognition events during virus morphogenesis, and are also relevant for the development of anti-HIV drugs that are able to interfere with capsid assembly or disassembly.
Topics: Capsid Proteins; HIV-1; Protein Conformation; Protein Multimerization; Protein Subunits; Virus Assembly
PubMed: 19825044
DOI: 10.1111/j.1742-4658.2009.07313.x -
Viruses Jan 2022The hepatitis C virus (HCV) co-opts numerous cellular elements, including proteins, lipids, and microRNAs, to complete its viral life cycle. The cellular RNA-binding...
The hepatitis C virus (HCV) co-opts numerous cellular elements, including proteins, lipids, and microRNAs, to complete its viral life cycle. The cellular RNA-binding protein, poly(rC)-binding protein 1 (PCBP1), was previously reported to bind to the 5' untranslated region (UTR) of the HCV genome; however, its importance in the viral life cycle has remained unclear. Herein, we sought to clarify the role of PCBP1 in the HCV life cycle. Using the HCV cell culture (HCVcc) system, we found that knockdown of endogenous PCBP1 resulted in an overall decrease in viral RNA accumulation, yet resulted in an increase in extracellular viral titers. To dissect PCBP1's specific role in the HCV life cycle, we carried out assays for viral entry, translation, genome stability, RNA replication, as well as virion assembly and secretion. We found that PCBP1 knockdown did not directly affect viral entry, translation, RNA stability, or RNA replication, but resulted in an overall increase in infectious particle secretion. This increase in virion secretion was evident even when viral RNA synthesis was inhibited, and blocking virus secretion could partially restore the viral RNA accumulation decreased by PCBP1 knockdown. We therefore propose a model where endogenous PCBP1 normally limits virion assembly and secretion, which increases viral RNA accumulation in infected cells by preventing the departure of viral genomes packaged into virions. Overall, our findings improve our understanding of how cellular RNA-binding proteins influence viral genomic RNA utilization during the HCV life cycle.
Topics: Cell Line; DNA-Binding Proteins; Hepacivirus; Humans; RNA, Viral; RNA-Binding Proteins; Viral Genome Packaging; Virion; Virus Assembly
PubMed: 35215884
DOI: 10.3390/v14020291 -
Viruses Oct 2011Insects are commonly infected with multiple viruses including those that cause sublethal, asymptomatic, and latent infections. Traditional methods for virus isolation... (Review)
Review
Insects are commonly infected with multiple viruses including those that cause sublethal, asymptomatic, and latent infections. Traditional methods for virus isolation typically lack the sensitivity required for detection of such viruses that are present at low abundance. In this respect, next generation sequencing technologies have revolutionized methods for the discovery and identification of new viruses from insects. Here we review both traditional and modern methods for virus discovery, and outline analysis of transcriptome and small RNA data for identification of viral sequences. We will introduce methods for de novo assembly of viral sequences, identification of potential viral sequences from BLAST data, and bioinformatics for generating full-length or near full-length viral genome sequences. We will also discuss implications of the ubiquity of viruses in insects and in insect cell lines. All of the methods described in this article can also apply to the discovery of viruses in other organisms.
Topics: Animals; Cell Line; Gene Expression Profiling; Genome, Viral; Genomics; High-Throughput Nucleotide Sequencing; Insect Viruses; Insecta; RNA, Viral; Sequence Analysis, DNA; Transcriptome; Virus Assembly
PubMed: 22069519
DOI: 10.3390/v3101849 -
Journal of Molecular Biology Jul 2011The pressing need to develop antivirals active against resistant strains of HIV-1 has led to efforts to target steps in the virus life cycle other than reverse... (Review)
Review
The pressing need to develop antivirals active against resistant strains of HIV-1 has led to efforts to target steps in the virus life cycle other than reverse transcription and Gag proteolysis. Among those steps are entry, integration, and assembly and/or maturation. Advances in understanding the structural biology of both the immature and the mature forms of the HIV capsid have made it possible to design or discover small molecules and peptides that interfere with both assembly and maturation. Here, we review the current state of the art in assembly and maturation inhibitors.
Topics: Anti-HIV Agents; Capsid Proteins; HIV-1; Humans; Models, Molecular; Virus Assembly
PubMed: 21762804
DOI: 10.1016/j.jmb.2011.03.074