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Viruses Nov 2023Porcine reproductive and respiratory syndrome virus (PRRSV) is globally prevalent and seriously harms the economic efficiency of pig farming. Because of its... (Review)
Review
Porcine reproductive and respiratory syndrome virus (PRRSV) is globally prevalent and seriously harms the economic efficiency of pig farming. Because of its immunosuppression and high incidence of mutant recombination, PRRSV poses a great challenge for disease prevention and control. Nonstructural protein 2 (NSP2) is the most variable functional protein in the PRRSV genome and can generate NSP2N and NSP2TF variants due to programmed ribosomal frameshifts. These variants are broad and complex in function and play key roles in numerous aspects of viral protein maturation, viral particle assembly, regulation of immunity, autophagy, apoptosis, cell cycle and cell morphology. In this paper, we review the structural composition, programmed ribosomal frameshift and biological properties of NSP2 to facilitate basic research on PRRSV and to provide theoretical support for disease prevention and control and therapeutic drug development.
Topics: Animals; Swine; Porcine respiratory and reproductive syndrome virus; Viral Nonstructural Proteins; Cell Line; Gene Expression; Frameshifting, Ribosomal; Porcine Reproductive and Respiratory Syndrome
PubMed: 38140551
DOI: 10.3390/v15122310 -
Life Sciences Oct 2023The intracellular production of reactive oxygen species (ROS), composed of oxygen-reduced molecules, is important not only because of their lethal effects on... (Review)
Review
The intracellular production of reactive oxygen species (ROS), composed of oxygen-reduced molecules, is important not only because of their lethal effects on microorganisms but also due to their potential inflammatory and metabolic regulation properties. The ROS pro-inflammatory properties are associated with the second signal to inflammasome activation, leading to cleaving pro-IL-1β and pro-IL18 before their secretion, as well as gasdermin-D, leading to pyroptosis. Some microorganisms can modulate NLRP3 and AIM-2 inflammasomes through ROS production: whilst Mycobacterium bovis, Mycobacterium kansasii, Francisella novicida, Brucella abortus, Listeria monocytogenes, Influenza virus, Syncytial respiratory virus, Porcine reproductive and respiratory syndrome virus, SARS-CoV, Mayaro virus, Leishmania amazonensis and Plasmodium sp. enhance inflammasome assembly, Hepatitis B virus, Mycobacterium marinum, Mycobacterium tuberculosis, Francisella tularensis and Leishmania sp. disrupt it. This process represents a recent cornerstone in our knowledge of the immunology of intracellular pathogens, which is reviewed in this mini-review.
Topics: Swine; Animals; Reactive Oxygen Species; Inflammasomes; Oxygen; Hepatitis B virus; Microbial Interactions
PubMed: 37683723
DOI: 10.1016/j.lfs.2023.122076 -
MBio Apr 2024A member of the Retroviridae, human immunodeficiency virus type 1 (HIV-1), uses the RNA genome packaged into nascent virions to transfer genetic information to its... (Review)
Review
A member of the Retroviridae, human immunodeficiency virus type 1 (HIV-1), uses the RNA genome packaged into nascent virions to transfer genetic information to its progeny. The genome packaging step is a highly regulated and extremely efficient process as a vast majority of virus particles contain two copies of full-length unspliced HIV-1 RNA that form a dimer. Thus, during virus assembly HIV-1 can identify and selectively encapsidate HIV-1 unspliced RNA from an abundant pool of cellular RNAs and various spliced HIV-1 RNAs. Several "" features facilitate the packaging of a dimeric RNA genome. The viral polyprotein ag orchestrates virus assembly and mediates RNA genome packaging. During this process, Gag preferentially binds unpaired uanosines within the highly structured 5' untranslated region (UTR) of HIV-1 RNA. In addition, the HIV-1 unspliced RNA provides a scaffold that promotes Gag:Gag interactions and virus assembly, thereby ensuring its packaging. Intriguingly, recent studies have shown that the use of different uanosines at the junction of U3 and R as transcription start sites results in HIV-1 unspliced RNA species with 99.9% identical sequences but dramatically distinct 5' UTR conformations. Consequently, one species of unspliced RNA is preferentially packaged over other nearly identical RNAs. These studies reveal how conformations affect the functions of HIV-1 RNA elements and the complex regulation of HIV-1 replication. In this review, we summarize - and -acting elements critical for HIV-1 RNA packaging, locations of Gag:RNA interactions that mediate genome encapsidation, and the effects of transcription start sites on the structure and packaging of HIV-1 RNA.
Topics: Humans; HIV-1; RNA, Viral; Virus Assembly; Genome, Viral
PubMed: 38411060
DOI: 10.1128/mbio.00861-23 -
Annual Review of Virology Sep 2023Phase separation of viral biopolymers is a key factor in the formation of cytoplasmic viral inclusions, known as sites of virus replication and assembly. This review... (Review)
Review
Phase separation of viral biopolymers is a key factor in the formation of cytoplasmic viral inclusions, known as sites of virus replication and assembly. This review describes the mechanisms and factors that affect phase separation in viral replication and identifies potential areas for future research. Drawing inspiration from studies on cellular RNA-rich condensates, we compare the hierarchical coassembly of ribosomal RNAs and proteins in the nucleolus to the coordinated coassembly of viral RNAs and proteins taking place within viral factories in viruses containing segmented RNA genomes. We highlight the common characteristics of biomolecular condensates in viral replication and how this new understanding is reshaping our views of virus assembly mechanisms. Such studies have the potential to uncover unexplored antiviral strategies targeting these phase-separated states.
Topics: Biomolecular Condensates; Cell Line; Viruses; Virus Replication; RNA
PubMed: 37040799
DOI: 10.1146/annurev-virology-111821-103226 -
Journal of Molecular Biology Aug 2023The past decade has seen a revolution in our understanding of how the cellular environment is organized, where an incredible body of work has provided new insights into... (Review)
Review
The past decade has seen a revolution in our understanding of how the cellular environment is organized, where an incredible body of work has provided new insights into the role played by membraneless organelles. These rapid advancements have been made possible by an increasing awareness of the peculiar physical properties that give rise to such bodies and the complex biology that enables their function. Viral infections are not extraneous to this. Indeed, in host cells, viruses can harness existing membraneless compartments or, even, induce the formation of new ones. By hijacking the cellular machinery, these intracellular bodies can assist in the replication, assembly, and packaging of the viral genome as well as in the escape of the cellular immune response. Here, we provide a perspective on the fundamental polymer physics concepts that may help connect and interpret the different observed phenomena, ranging from the condensation of viral genomes to the phase separation of multicomponent solutions. We complement the discussion of the physical basis with a description of biophysical methods that can provide quantitative insights for testing and developing theoretical and computational models.
Topics: Humans; Organelles; Virus Diseases; Biomolecular Condensates; Virus Replication; Viral Genome Packaging; Stress Granules; Genome, Viral; Biopolymers; Phase Transition
PubMed: 36709795
DOI: 10.1016/j.jmb.2023.167988 -
Frontiers in Cellular and Infection... 2023The inflammasome is a multiprotein complex that further regulates cell pyroptosis and inflammation by activating caspase-1. The assembly and activation of inflammasome... (Review)
Review
The inflammasome is a multiprotein complex that further regulates cell pyroptosis and inflammation by activating caspase-1. The assembly and activation of inflammasome are associated with a variety of diseases. Accumulative studies have shown that inflammasome is a key modulator of the host's defense response to viral infection. Indeed, it has been established that activation of inflammasome occurs during viral infection. At the same time, the host has evolved a variety of corresponding mechanisms to inhibit unnecessary inflammasome activation. Therefore, here, we review and summarize the latest research progress on the interaction between inflammosomes and viruses, highlight the assembly and activation of inflammosome in related cells after viral infection, as well as the corresponding molecular regulatory mechanisms, and elucidate the effects of this activation on virus immune escape and host innate and adaptive immune defenses. Finally, we also discuss the potential therapeutic strategies to prevent and/or ameliorate viral infection-related diseases via targeting inflammasomes and its products.
Topics: Humans; Inflammasomes; Virus Diseases; Viruses; Host Microbial Interactions; Animals
PubMed: 37465759
DOI: 10.3389/fcimb.2023.1173505 -
Acta Biochimica Et Biophysica Sinica Jul 2023Liquid-liquid phase separation (LLPS) has emerged as a crucial mechanism for cellular compartmentalization. One prominent example of this is the stress granule. Found in...
Liquid-liquid phase separation (LLPS) has emerged as a crucial mechanism for cellular compartmentalization. One prominent example of this is the stress granule. Found in various types of cells, stress granule is a biomolecular condensate formed through phase separation. It comprises numerous RNA and RNA-binding proteins. Over the past decades, substantial knowledge has been gained about the composition and dynamics of stress granules. SGs can regulate various signaling pathways and have been associated with numerous human diseases, such as neurodegenerative diseases, cancer, and infectious diseases. The threat of viral infections continues to loom over society. Both DNA and RNA viruses depend on host cells for replication. Intriguingly, many stages of the viral life cycle are closely tied to RNA metabolism in human cells. The field of biomolecular condensates has rapidly advanced in recent times. In this context, we aim to summarize research on stress granules and their link to viral infections. Notably, stress granules triggered by viral infections behave differently from the canonical stress granules triggered by sodium arsenite (SA) and heat shock. Studying stress granules in the context of viral infections could offer a valuable platform to link viral replication processes and host anti-viral responses. A deeper understanding of these biological processes could pave the way for innovative interventions and treatments for viral infectious diseases. They could potentially bridge the gap between basic biological processes and interactions between viruses and their hosts.
Topics: Humans; Cytoplasmic Granules; Stress Granules; RNA; Virus Diseases; Biological Phenomena; Virus Replication
PubMed: 37401177
DOI: 10.3724/abbs.2023117 -
Journal of Materials Chemistry. B Oct 2023Virus-like particles (VLPs) are self-assembled supramolecular structures found in nature, often used for compartmentalization. Exploiting their inherent properties,... (Review)
Review
Virus-like particles (VLPs) are self-assembled supramolecular structures found in nature, often used for compartmentalization. Exploiting their inherent properties, including precise nanoscale structures, monodispersity, and high stability, these architectures have been widely used as nanocarriers to protect or enrich catalysts, facilitating catalytic reactions and avoiding interference from the bulk solutions. In this review, we summarize the current progress of virus-like particles (VLPs)-based nanoreactors. First, we briefly introduce the physicochemical properties of the most commonly used virus particles to understand their roles in catalytic reactions beyond the confined space. Next, we summarize the self-assembly of nanoreactors forming higher-order hierarchical structures, highlighting the emerging field of nanoreactors as artificial organelles and their potential biomedical applications. Finally, we discuss the current findings and future perspectives of VLPs-based nanoreactors.
Topics: Catalysis; Virion; Nanotechnology
PubMed: 37697810
DOI: 10.1039/d3tb01112g -
Proceedings of the National Academy of... Jul 2023Retrotransposons and retroviruses shape genome evolution and can negatively impact genome function. and its close relatives harbor several families of...
Retrotransposons and retroviruses shape genome evolution and can negatively impact genome function. and its close relatives harbor several families of LTR-retrotransposons, the most abundant being Ty1 in several laboratory strains. The cytosolic foci that nucleate Ty1 virus-like particle (VLP) assembly are not well understood. These foci, termed retrosomes or T-bodies, contain Ty1 Gag and likely Gag-Pol and the Ty1 mRNA destined for reverse transcription. Here, we report an intrinsically disordered N-terminal ion-ike omain (PrLD) within Gag that is required for transposition. This domain contains amino acid composition similar to known yeast prions and is sufficient to nucleate prionogenesis in an established cell-based prion reporter system. Deleting the Ty1 PrLD results in dramatic VLP assembly and retrotransposition defects but does not affect Gag protein level. Ty1 Gag chimeras in which the PrLD is replaced with other sequences, including yeast and mammalian prionogenic domains, display a range of retrotransposition phenotypes from wild type to null. We examine these chimeras throughout the Ty1 replication cycle and find that some support retrosome formation, VLP assembly, and retrotransposition, including the yeast Sup35 prion and the mouse PrP prion. Our interchangeable Ty1 system provides a useful, genetically tractable in vivo platform for studying PrLDs, complete with a suite of robust and sensitive assays. Our work also invites study into the prevalence of PrLDs in additional mobile elements.
Topics: Animals; Mice; Saccharomyces cerevisiae; Retroelements; RNA, Messenger; Gene Products, gag; Virus Assembly; Mammals
PubMed: 37459521
DOI: 10.1073/pnas.2303358120 -
Microbiology Spectrum Feb 2024Assembly of infectious hepatitis C virus (HCV) particles requires multiple cellular proteins including for instance apolipoprotein E (ApoE). To describe these... (Review)
Review
Assembly of infectious hepatitis C virus (HCV) particles requires multiple cellular proteins including for instance apolipoprotein E (ApoE). To describe these protein-protein interactions, we performed an affinity purification mass spectrometry screen of HCV-infected cells. We used functional viral constructs with epitope-tagged envelope protein 2 (E2), protein (p) 7, or nonstructural protein 4B (NS4B) as well as cells expressing a tagged variant of ApoE. We also evaluated assembly stage-dependent remodeling of protein complexes by using viral mutants carrying point mutations abrogating particle production at distinct steps of the HCV particle production cascade. Five ApoE binding proteins, 12 p7 binders, 7 primary E2 interactors, and 24 proteins interacting with NS4B were detected. Cell-derived PREB, STT3B, and SPCS2 as well as viral NS2 interacted with both p7 and E2. Only GTF3C3 interacted with E2 and NS4B, highlighting that HCV assembly and replication complexes exhibit largely distinct interactomes. An HCV core protein mutation, preventing core protein decoration of lipid droplets, profoundly altered the E2 interactome. In cells replicating this mutant, E2 interactions with HSPA5, STT3A/B, RAD23A/B, and ZNF860 were significantly enhanced, suggesting that E2 protein interactions partly depend on core protein functions. Bioinformatic and functional studies including STRING network analyses, RNA interference, and ectopic expression support a role of Rad23A and Rad23B in facilitating HCV infectious virus production. Both Rad23A and Rad23B are involved in the endoplasmic reticulum (ER)-associated protein degradation (ERAD). Collectively, our results provide a map of host proteins interacting with HCV assembly proteins, and they give evidence for the involvement of ER protein folding machineries and the ERAD pathway in the late stages of the HCV replication cycle.IMPORTANCEHepatitis C virus (HCV) establishes chronic infections in the majority of exposed individuals. This capacity likely depends on viral immune evasion strategies. One feature likely contributing to persistence is the formation of so-called lipo-viro particles. These peculiar virions consist of viral structural proteins and cellular lipids and lipoproteins, the latter of which aid in viral attachment and cell entry and likely antibody escape. To learn about how lipo-viro particles are coined, here, we provide a comprehensive overview of protein-protein interactions in virus-producing cells. We identify numerous novel and specific HCV E2, p7, and cellular apolipoprotein E-interacting proteins. Pathway analyses of these interactors show that proteins participating in processes such as endoplasmic reticulum (ER) protein folding, ER-associated protein degradation, and glycosylation are heavily engaged in virus production. Moreover, we find that the proteome of HCV replication sites is distinct from the assembly proteome, suggesting that transport process likely shuttles viral RNA to assembly sites.
Topics: Humans; Hepacivirus; Viral Nonstructural Proteins; Proteome; Cell Line; Hepatitis C; Apolipoproteins E; Apolipoproteins; DNA-Binding Proteins; DNA Repair Enzymes
PubMed: 38230952
DOI: 10.1128/spectrum.02562-22