The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Peter D. Nagy - One of the best experts on this subject based on the ideXlab platform.
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Taking over Cellular Energy-Metabolism for TBSV Replication: The High ATP Requirement of an RNA Virus within the Viral Replication Organelle.
Viruses, 2020Co-Authors: Peter D. Nagy, Wenwu LinAbstract:Recent discoveries on virus-driven hijacking and compartmentalization of the cellular glycolytic and fermentation pathways to support robust virus Replication put the spotlight on the energy requirement of Viral processes. The active recruitment of glycolytic enzymes in combination with fermentation enzymes by the Viral Replication proteins emphasizes the advantages of producing ATP locally within Viral Replication structures. This leads to a paradigm shift in our understanding of how viruses take over host metabolism to support the virus's energy needs during the Replication process. This review highlights our current understanding of how a small plant virus, Tomato bushy stunt virus, exploits a conserved energy-generating cellular pathway during Viral Replication. The emerging picture is that viruses not only rewire cellular metabolic pathways to obtain the necessary resources from the infected cells but the fast replicating viruses might have to actively hijack and compartmentalize the energy-producing enzymes to provide a readily available source of ATP for Viral Replication process.
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Enrichment of Phosphatidylethanolamine in Viral Replication Compartments via Co-opting the Endosomal Rab5 Small GTPase by a Positive-Strand RNA Virus.
PLoS biology, 2016Co-Authors: Peter D. NagyAbstract:Positive-strand RNA viruses build extensive membranous Replication compartments to support Replication and protect the virus from antiViral responses by the host. These viruses require host factors and various lipids to form Viral Replication complexes (VRCs). The VRCs built by Tomato bushy stunt virus (TBSV) are enriched with phosphatidylethanolamine (PE) through a previously unknown pathway. To unravel the mechanism of PE enrichment within the TBSV Replication compartment, in this paper, the authors demonstrate that TBSV co-opts the guanosine triphosphate (GTP)-bound active form of the endosomal Rab5 small GTPase via direct interaction with the Viral Replication protein. Deletion of Rab5 orthologs in a yeast model host or expression of dominant negative mutants of plant Rab5 greatly decreases TBSV Replication and prevents the redistribution of PE to the sites of Viral Replication. We also show that enrichment of PE in the Viral Replication compartment is assisted by actin filaments. Interestingly, the closely related Carnation Italian ringspot virus, which replicates on the boundary membrane of mitochondria, uses a similar strategy to the peroxisomal TBSV to hijack the Rab5-positive endosomes into the Viral Replication compartments. Altogether, usurping the GTP-Rab5-positive endosomes allows TBSV to build a PE-enriched Viral Replication compartment, which is needed to support peak-level Replication. Thus, the Rab family of small GTPases includes critical host factors assisting VRC assembly and genesis of the Viral Replication compartment.
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Making of Viral Replication organelles by remodeling interior membranes.
Viruses, 2010Co-Authors: Zsuzsanna Sasvari, Peter D. NagyAbstract:Positive-stranded RNA (+RNA) viruses exploit host cell machinery by subverting host proteins and membranes and altering cellular pathways during infection. To achieve robust Replication, some +RNA viruses, such as poliovirus (PV), build special intracellular compartments, called Viral Replication organelles. A recent work from the Altan-Bonnett laboratory [1] gave new insights into the formation of poliovirus Replication organelles, which are unique subcellular structures containing many individual Replication complexes as a result of dynamic cellular membrane remodeling.
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Multiple roles of Viral Replication proteins in plant RNA virus Replication.
Methods in molecular biology (Clifton N.J.), 2008Co-Authors: Peter D. Nagy, Judit PoganyAbstract:Identification of the roles of Replication factors represents one of the major frontiers in current virus research. Among plant viruses, the positive-stranded (+) RNA viruses are the largest group and the most widespread. The central step in the infection cycles of (+) RNA viruses is RNA Replication, which leads to rapid production of huge number of Viral (+) RNA progeny in the infected plant cells. The RNA Replication process is carried out by the virus-specific replicase complex consisting of Viral RNA-dependent RNA polymerase, one or more auxiliary Viral Replication proteins, and host factors, which assemble in specialized membranous compartments in infected cells. Replication is followed by cell-to-cell and long-distance movement to invade the entire plant and/or encapsidation to facilitate transmission to new plants. This chapter provides an overview of our current understanding of the role of Viral Replication proteins during genome Replication. The recent significant progress in this research area is based on development of powerful in vivo and in vitro approaches, including replicase assays, reverse genetic approaches, intracelular localization studies and the use of plant or yeast model hosts.
Juan Reguera - One of the best experts on this subject based on the ideXlab platform.
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capping pores of alphavirus nsp1 gate membranous Viral Replication factories
Nature, 2021Co-Authors: Rhian Jones, Gabriel Bragagnolo, Rocio Arranz, Juan RegueraAbstract:Positive-sense single-stranded RNA viruses, such as coronaviruses, flaviviruses and alphaviruses, carry out transcription and Replication inside virus-induced membranous organelles within host cells1–7. The remodelling of the host-cell membranes for the formation of these organelles is coupled to the membrane association of Viral Replication complexes and to RNA synthesis. These Viral niches allow for the concentration of metabolites and proteins for the synthesis of Viral RNA, and prevent the detection of this RNA by the cellular innate immune system8. Here we present the cryo-electron microscopy structure of non-structural protein 1 (nsP1) of the alphavirus chikungunya virus, which is responsible for RNA capping and membrane binding of the Viral Replication machinery. The structure shows the enzyme in its active form, assembled in a monotopic membrane-associated dodecameric ring. The structure reveals the structural basis of the coupling between membrane binding, oligomerization and allosteric activation of the capping enzyme. The stoichiometry—with 12 active sites in a single complex—redefines Viral Replication complexes as RNA synthesis reactors. The ring shape of the complex implies it has a role in controlling access to the Viral organelle and ensuring the exit of properly capped Viral RNA. Our results provide high-resolution information about the membrane association of the Replication machinery of positive-sense single-stranded RNA viruses, and open up avenues for the further characterization of Viral Replication on cell membranes and the generation of antiViral agents. Cryo-electron microscopy structures of non-structural protein 1 (nsP1) of chikungunya virus reveal the mechanisms that underpin the association of Viral Replication machinery with virus-induced membranous organelles within host cells.
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Capping pores of alphavirus nsP1 gate membranous Viral Replication factories.
Nature, 2020Co-Authors: Rhian Jones, Gabriel Bragagnolo, Rocio Arranz, Juan RegueraAbstract:Positive-sense single-stranded RNA viruses, such as coronaviruses, flaviviruses and alphaviruses, carry out transcription and Replication inside virus-induced membranous organelles within host cells1-7. The remodelling of the host-cell membranes for the formation of these organelles is coupled to the membrane association of Viral Replication complexes and to RNA synthesis. These Viral niches allow for the concentration of metabolites and proteins for the synthesis of Viral RNA, and prevent the detection of this RNA by the cellular innate immune system8. Here we present the cryo-electron microscopy structure of non-structural protein 1 (nsP1) of the alphavirus chikungunya virus, which is responsible for RNA capping and membrane binding of the Viral Replication machinery. The structure shows the enzyme in its active form, assembled in a monotopic membrane-associated dodecameric ring. The structure reveals the structural basis of the coupling between membrane binding, oligomerization and allosteric activation of the capping enzyme. The stoichiometry-with 12 active sites in a single complex-redefines Viral Replication complexes as RNA synthesis reactors. The ring shape of the complex implies it has a role in controlling access to the Viral organelle and ensuring the exit of properly capped Viral RNA. Our results provide high-resolution information about the membrane association of the Replication machinery of positive-sense single-stranded RNA viruses, and open up avenues for the further characterization of Viral Replication on cell membranes and the generation of antiViral agents.
Victoria E. Walker-sperling - One of the best experts on this subject based on the ideXlab platform.
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Factors Associated With the Control of Viral Replication and Virologic Breakthrough in a Recently Infected HIV-1 Controller
EBioMedicine, 2017Co-Authors: Victoria E. Walker-sperling, Christopher W. Pohlmeyer, Rebecca T. Veenhuis, Megan May, Krystle A. Luna, Allison R. Kirkpatrick, Oliver Laeyendecker, Andrea L. Cox, Mary Carrington, Justin R. BaileyAbstract:Abstract HIV-1 controllers are patients who control HIV-1 Viral Replication without antiretroViral therapy. Control is achieved very early in the course of infection, but the mechanisms through which Viral Replication is restricted are not fully understood. We describe a patient who presented with acute HIV-1 infection and was found to have an HIV-1 RNA level of
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Short Communication: HIV Controller T Cells Effectively Inhibit Viral Replication in Alveolar Macrophages.
AIDS research and human retroviruses, 2016Co-Authors: Victoria E. Walker-sperling, Christian A. Merlo, Robert W. Buckheit, Allison Lambert, Patrick M. Tarwater, Greg D. Kirk, M. Bradley Drummond, Joel N. BlanksonAbstract:Abstract Macrophages are targets of HIV-1 infection, and control of Viral Replication within these cells may be an important component of a T-cell-based vaccine. Although several studies have analyzed the ability of CD8+ T cells to inhibit Viral Replication in monocyte-derived macrophages, the effect of T cells on HIV-1-infected tissue macrophages is less clear. We demonstrate here that both CD4+ and CD8+ T-cell effectors from HIV controllers are capable of suppressing Viral Replication in bronchoalveolar lavage-derived alveolar macrophages. These findings have implications for HIV-1 vaccine and eradication strategies.
Wenwu Lin - One of the best experts on this subject based on the ideXlab platform.
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Taking over Cellular Energy-Metabolism for TBSV Replication: The High ATP Requirement of an RNA Virus within the Viral Replication Organelle.
Viruses, 2020Co-Authors: Peter D. Nagy, Wenwu LinAbstract:Recent discoveries on virus-driven hijacking and compartmentalization of the cellular glycolytic and fermentation pathways to support robust virus Replication put the spotlight on the energy requirement of Viral processes. The active recruitment of glycolytic enzymes in combination with fermentation enzymes by the Viral Replication proteins emphasizes the advantages of producing ATP locally within Viral Replication structures. This leads to a paradigm shift in our understanding of how viruses take over host metabolism to support the virus's energy needs during the Replication process. This review highlights our current understanding of how a small plant virus, Tomato bushy stunt virus, exploits a conserved energy-generating cellular pathway during Viral Replication. The emerging picture is that viruses not only rewire cellular metabolic pathways to obtain the necessary resources from the infected cells but the fast replicating viruses might have to actively hijack and compartmentalize the energy-producing enzymes to provide a readily available source of ATP for Viral Replication process.
Xiaofeng Wang - One of the best experts on this subject based on the ideXlab platform.
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An engineered mutant of a host phospholipid synthesis gene inhibits Viral Replication without compromising host fitness.
The Journal of biological chemistry, 2019Co-Authors: Zhenlu Zhang, Preethi Sathanantham, Xin Zhang, Lianhui Xie, Xiaofeng WangAbstract:Viral infections universally rely on numerous hijacked host factors to be successful. It is therefore possible to control Viral infections by manipulating host factors that are critical for Viral Replication. Given that host genes may play essential roles in certain cellular processes, any successful manipulations for virus control should cause no or mild effects on host fitness. We previously showed that a group of positive-strand RNA viruses enrich phosphatidylcholine (PC) at the sites of Viral Replication. Specifically, brome mosaic virus (BMV) Replication protein 1a interacts with and recruits a PC synthesis enzyme, phosphatidylethanolamine methyltransferase, Cho2p, to the Viral Replication sites that are assembled on the perinuclear endoplasmic reticulum (ER) membrane. Deletion of the CHO2 gene inhibited BMV Replication by 5-fold; however, it slowed down host cell growth as well. Here, we show that an engineered Cho2p mutant supports general PC synthesis and normal cell growth but blocks BMV Replication. This mutant interacts and colocalizes with BMV 1a but prevents BMV 1a from localizing to the perinuclear ER membrane. The mislocalized BMV 1a fails to induce the formation of Viral Replication complexes. Our study demonstrates an effective antiViral strategy in which a host lipid synthesis gene is engineered to control Viral Replication without comprising host growth.
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Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at Viral Replication sites.
Proceedings of the National Academy of Sciences of the United States of America, 2016Co-Authors: Jiantao Zhang, Zhenlu Zhang, Vineela Chukkapalli, Jules A. Nchoutmboube, Glenn Randall, George A. Belov, Xiaofeng WangAbstract:All positive-strand RNA viruses reorganize host intracellular membranes to assemble their Viral Replication complexes (VRCs); however, how these viruses modulate host lipid metabolism to accommodate such membrane proliferation and rearrangements is not well defined. We show that a significantly increased phosphatidylcholine (PC) content is associated with brome mosaic virus (BMV) Replication in both natural host barley and alternate host yeast based on a lipidomic analysis. Enhanced PC levels are primarily associated with the perinuclear ER membrane, where BMV Replication takes place. More specifically, BMV Replication protein 1a interacts with and recruits Cho2p (choline requiring 2), a host enzyme involved in PC synthesis, to the site of Viral Replication. These results suggest that PC synthesized at the site of VRC assembly, not the transport of existing PC, is responsible for the enhanced accumulation. Blocking PC synthesis by deleting the CHO2 gene resulted in VRCs with wider diameters than those in wild-type cells; however, BMV Replication was significantly inhibited, highlighting the critical role of PC in VRC formation and Viral Replication. We further show that enhanced PC levels also accumulate at the Replication sites of hepatitis C virus and poliovirus, revealing a conserved feature among a group of positive-strand RNA viruses. Our work also highlights a potential broad-spectrum antiViral strategy that would disrupt PC synthesis at the sites of Viral Replication but would not alter cellular processes.
