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Science (New York, N.Y.) Aug 2021
Topics: HIV-1; Humans; Virus Assembly; Virus Replication
PubMed: 34353938
DOI: 10.1126/science.abj9075 -
Sub-cellular Biochemistry 2023During respiratory syncytial virus (RSV) particle assembly, the mature RSV particles form as filamentous projections on the surface of RSV-infected cells. The RSV... (Review)
Review
During respiratory syncytial virus (RSV) particle assembly, the mature RSV particles form as filamentous projections on the surface of RSV-infected cells. The RSV assembly process occurs at the / on the cell surface that is modified by a virus infection, involving a combination of several different host cell factors and cellular processes. This induces changes in the lipid composition and properties of these lipid microdomains, and the virus-induced activation of associated Rho GTPase signaling networks drives the remodeling of the underlying filamentous actin (F-actin) cytoskeleton network. The modified sites that form on the surface of the infected cells form the nexus point for RSV assembly, and in this review chapter, they are referred to as the RSV assembleome. This is to distinguish these unique membrane microdomains that are formed during virus infection from the corresponding membrane microdomains that are present at the cell surface prior to infection. In this article, an overview of the current understanding of the processes that drive the formation of the assembleome during RSV particle assembly is given.
Topics: Humans; Virus Assembly; Respiratory Syncytial Virus, Human; Cell Membrane; Virus Diseases; Lipids
PubMed: 38159230
DOI: 10.1007/978-3-031-40086-5_9 -
MBio Oct 2021In 2019, a new pandemic virus belonging to the betacoronavirus family emerged, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This new coronavirus...
In 2019, a new pandemic virus belonging to the betacoronavirus family emerged, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This new coronavirus appeared in Wuhan, China, and is responsible for severe respiratory pneumonia in humans, namely, coronavirus disease 2019 (COVID-19). Having infected almost 200 million people worldwide and caused more than 4.1 million deaths as of today, this new disease has raised a significant number of questions about its molecular mechanism of replication and, in particular, how infectious viral particles are produced. Although viral entry is well characterized, the full assembly steps of SARS-CoV-2 have still not been fully described. Coronaviruses, including SARS-CoV-2, have four main structural proteins, namely, the spike glycoprotein (S), the membrane glycoprotein (M), the envelope protein (E), and the nucleocapsid protein (N). All these proteins have key roles in the process of coronavirus assembly and budding. In this review, we gathered the current knowledge about betacoronavirus structural proteins involved in viral particle assembly, membrane curvature and scission, and then egress in order to suggest and question a coherent model for SARS-CoV-2 particle production and release.
Topics: Betacoronavirus; Membrane Glycoproteins; Nucleocapsid Proteins; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Assembly
PubMed: 34579570
DOI: 10.1128/mBio.02371-21 -
Current Opinion in Virology Dec 2020Viral structural proteins are emerging as effective targets for new antivirals. In a viral lifecycle, the capsid must assemble, disassemble, and respond to host... (Review)
Review
Viral structural proteins are emerging as effective targets for new antivirals. In a viral lifecycle, the capsid must assemble, disassemble, and respond to host proteins, all at the right time and place. These reactions work within a narrow range of conditions, making them susceptible to small molecule interference. In at least three specific viruses, this approach has had met with preliminary success. In rhinovirus and poliovirus, compounds like pleconaril bind capsid and block RNA release. Bevirimat binds to Gag protein in HIV, inhibiting maturation. In Hepatitis B virus, core protein allosteric modulators (CpAMs) promote spontaneous assembly of capsid protein leading to empty and aberrant particles. Despite the biological diversity between viruses and the chemical diversity between antiviral molecules, we observe common features in these antivirals' mechanisms of action. These approaches work by stabilizing protein-protein interactions.
Topics: Antiviral Agents; Capsid; Drug Discovery; Hepatitis B virus; Viral Structural Proteins; Virus Assembly; Virus Replication; Viruses
PubMed: 32777753
DOI: 10.1016/j.coviro.2020.07.001 -
Viruses Dec 2021The assembly of human cytomegalovirus (HCMV) and other herpesviruses includes both nuclear and cytoplasmic phases. During the prolonged replication cycle of HCMV, the... (Review)
Review
The assembly of human cytomegalovirus (HCMV) and other herpesviruses includes both nuclear and cytoplasmic phases. During the prolonged replication cycle of HCMV, the cell undergoes remarkable changes in cellular architecture that include marked increases in nuclear size and structure as well as the reorganization of membranes in cytoplasm. Similarly, significant changes occur in cellular metabolism, protein trafficking, and cellular homeostatic functions. These cellular modifications are considered integral in the efficient assembly of infectious progeny in productively infected cells. Nuclear egress of HCMV nucleocapsids is thought to follow a pathway similar to that proposed for other members of the herpesvirus family. During this process, viral nucleocapsids must overcome structural barriers in the nucleus that limit transit and, ultimately, their delivery to the cytoplasm for final assembly of progeny virions. HCMV, similar to other herpesviruses, encodes viral functions that co-opt cellular functions to overcome these barriers and to bridge the bilaminar nuclear membrane. In this brief review, we will highlight some of the mechanisms that define our current understanding of HCMV egress, relying heavily on the current understanding of egress of the more well-studied α-herpesviruses, HSV-1 and PRV.
Topics: Capsid; Cell Nucleus; Cytomegalovirus; Cytoplasm; DNA Replication; DNA, Viral; Humans; Nuclear Envelope; Nucleocapsid; Viral Genome Packaging; Virus Release; Virus Replication
PubMed: 35062219
DOI: 10.3390/v14010015 -
Molecular Microbiology Jun 2022Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of congenital disabilities as well as a significant cause of disease in immunocompromised... (Review)
Review
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of congenital disabilities as well as a significant cause of disease in immunocompromised patients. The envelopment and egress of HCMV particles is an essential step of the viral life cycle as it determines viral spread and potentially tropism. Here we review the current literature on HCMV envelopment and egress with a particular focus on the role of virus-containing multivesicular body-like vesicles for virus egress and spread. We discuss the difficulties of determining the cellular provenance of these structures in light of viral redistribution of cellular marker proteins and provide potential paths to illuminate their genesis. Finally, we discuss how divergent egress pathways could result in virions of different tropisms.
Topics: Cytomegalovirus; Humans; Proteins; Virion; Virus Assembly
PubMed: 35607767
DOI: 10.1111/mmi.14946 -
ACS Nano Jan 2022Simple RNA viruses self-assemble spontaneously and encapsulate their genome into a shell called the capsid. This process is mainly driven by the attractive...
Simple RNA viruses self-assemble spontaneously and encapsulate their genome into a shell called the capsid. This process is mainly driven by the attractive electrostatics interaction between the positive charges on capsid proteins and the negative charges on the genome. Despite its importance and many decades of intense research, how the virus selects and packages its native RNA inside the crowded environment of a host cell cytoplasm in the presence of an abundance of nonviral RNA and other anionic polymers has remained a mystery. In this paper, we perform a series of simulations to monitor the growth of viral shells and find the mechanism by which cargo-coat protein interactions can impact the structure and stability of the viral shells. We show that coat protein subunits can assemble around a globular nucleic acid core by forming nonicosahedral cages, which have been recently observed in assembly experiments involving small pieces of RNA. We find that the resulting cages are strained and can easily be split into fragments along stress lines. This suggests that such metastable nonicosahedral intermediates could be easily reassembled into the stable native icosahedral shells if the larger wild-type genome becomes available, despite the presence of a myriad of nonviral RNAs.
Topics: Virus Assembly; Capsid; Capsid Proteins; Viruses; RNA
PubMed: 35019271
DOI: 10.1021/acsnano.1c06335 -
Wiley Interdisciplinary Reviews.... Jul 2020Viruses are highly ordered supramolecular complexes that have evolved to propagate by hijacking the host cell's machinery. Although viruses are very diverse, spreading... (Review)
Review
Viruses are highly ordered supramolecular complexes that have evolved to propagate by hijacking the host cell's machinery. Although viruses are very diverse, spreading through cells of all kingdoms of life, they share common functions and properties. Next to the general interest in virology, fundamental viral mechanisms are of growing importance in other disciplines such as biomedicine and (bio)nanotechnology. However, in order to optimally make use of viruses and virus-like particles, for instance as vehicle for targeted drug delivery or as building blocks in electronics, it is essential to understand their basic chemical and physical properties and characteristics. In this context, the number of studies addressing the mechanisms governing viral properties and processes has recently grown drastically. This review summarizes a specific part of these scientific achievements, particularly addressing physical virology approaches aimed to understand the self-assembly of viruses and the mechanical properties of viral particles. Using a physicochemical perspective, we have focused on fundamental studies providing an overview of the molecular basis governing these key aspects of viral systems. This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
Topics: Biomechanical Phenomena; Genome, Viral; Humans; Virion; Virus Assembly; Viruses
PubMed: 31960585
DOI: 10.1002/wnan.1613 -
Cell Host & Microbe Nov 2019Dengue virus assembly requires cleavage of viral C-prM-E polyprotein into three structural proteins (capsid, premembrane, and envelope), packaging of viral RNA with C...
Dengue virus assembly requires cleavage of viral C-prM-E polyprotein into three structural proteins (capsid, premembrane, and envelope), packaging of viral RNA with C protein into nucleocapsid, and budding of prM and E proteins into virions. The molecular mechanisms underlying these assembly events are unclear. Here, we show that dengue nonstructural protein 2A (NS2A protein) recruits viral RNA, structural proteins, and protease to the site of virion assembly and coordinates nucleocapsid and virus formation. The last 285 nucleotides of viral 3' UTR serve as a "recruiting signal for packaging" that binds to a cytosolic loop of NS2A. This interaction allows NS2A to recruit nascent RNA from the replication complex to the virion assembly site. NS2A also recruits the C-prM-E polyprotein and NS2B-NS3 protease to the virion assembly site by interacting with prM, E, and NS3, leading to coordinated C-prM-E cleavage. Mature C protein assembles onto genomic RNA to form nucleocapsid, followed by prM and E envelopment and virion formation.
Topics: Aedes; Animals; Cell Line; Chlorocebus aethiops; Cricetinae; Dengue Virus; HEK293 Cells; Humans; Nucleocapsid; RNA Helicases; RNA, Viral; Serine Endopeptidases; Vero Cells; Viral Envelope Proteins; Viral Nonstructural Proteins; Viral Proteins; Virus Assembly
PubMed: 31631053
DOI: 10.1016/j.chom.2019.09.015 -
Microbiology and Immunology Oct 2019The family Flaviviridae comprises four genera, namely, Flavivirus, Pestivirus, Pegivirus, and Hepacivirus. These viruses have similar genome structures, but the genomes... (Review)
Review
The family Flaviviridae comprises four genera, namely, Flavivirus, Pestivirus, Pegivirus, and Hepacivirus. These viruses have similar genome structures, but the genomes of Pestivirus and Flavivirus encode the secretory glycoproteins E and NS1, respectively. E plays an important role in virus particle formation and cell entry, whereas NS1 participates in the formation of replication complexes and virus particles. Conversely, apolipoproteins are known to participate in the formation of infectious particles of hepatitis C virus (HCV) and various secretory glycoproteins play a similar role in HCV particles formation, suggesting that there is no strong specificity for the function of secretory glycoproteins in infectious-particle formation. In addition, recent studies have shown that host-derived apolipoproteins and virus-derived E and NS1 play comparable roles in infectious-particle formation of both HCV and pestiviruses. In this review, we summarize the roles of secretory glycoproteins in the formation of Flaviviridae virus particles.
Topics: Apolipoproteins; Flaviviridae; Flaviviridae Infections; Glycoproteins; Host Microbial Interactions; Humans; Virion; Virus Assembly
PubMed: 31342548
DOI: 10.1111/1348-0421.12733