244 results match your criteria vp35


Development of a New Reverse Genetics System for Ebola Virus.

mSphere 2021 May 5;6(3). Epub 2021 May 5.

Unit of Viral Hepatitis, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai, China

Ebola virus (EBOV) is a highly pathogenic negative-stranded RNA virus that has caused several deadly endemics in the past decades. EBOV reverse genetics systems are available for studying live viruses under biosafety level 4 (BSL-4) or subviral particles under BSL-2 conditions. However, these systems all require cotransfection of multiple plasmids expressing viral genome and viral proteins essential for EBOV replication, which is technically challenging and unable to naturally mimic virus propagation using the subviral particle. Read More

View Article and Full-Text PDF

Grass Carp Reovirus VP35 Degrades MAVS Through the Autophagy Pathway to Inhibit Fish Interferon Production.

Front Immunol 2021 23;12:613145. Epub 2021 Mar 23.

Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Fish interferon (IFN) is a crucial cytokine for a host to resist external pathogens, conferring cells with antiviral capacity. Meanwhile, grass carp reovirus (GCRV) is a strong pathogen that causes high mortality in grass carp. Therefore, it is necessary to study the strategy used by GCRV to evade the cellular IFN response. Read More

View Article and Full-Text PDF

Crystal structure of human LC8 bound to a peptide from Ebola virus VP35.

J Microbiol 2021 Apr 25;59(4):410-416. Epub 2021 Feb 25.

Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.

Zaire ebolavirus, commonly called Ebola virus (EBOV), is an RNA virus that causes severe hemorrhagic fever with high mortality. Viral protein 35 (VP35) is a virulence factor encoded in the EBOV genome. VP35 inhibits host innate immune responses and functions as a critical cofactor for viral RNA replication. Read More

View Article and Full-Text PDF

Oral Vaccination of Grass Carp () with Baculovirus-Expressed Grass Carp Reovirus (GCRV) Proteins Induces Protective Immunity against GCRV Infection.

Vaccines (Basel) 2021 Jan 12;9(1). Epub 2021 Jan 12.

Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China.

The grass carp reovirus (GCRV) causes severe hemorrhagic disease with high mortality and leads to serious economic losses in the grass carp () industry in China. Oral vaccine has been proven to be an effective method to provide protection against fish viruses. In this study, a recombinant baculovirus BmNPV-VP35-VP4 was generated to express VP35 and VP4 proteins from GCRV type Ⅱ via Bac-to-Bac baculovirus expression system. Read More

View Article and Full-Text PDF
January 2021

Transcriptional Analysis of Lymphoid Tissues from Infected Nonhuman Primates Reveals the Basis for Attenuation and Immunogenicity of an Ebola Virus Encoding a Mutant VP35 Protein.

J Virol 2021 02 24;95(6). Epub 2021 Feb 24.

Department of Molecular Biology and Biochemistry, College of Biological Sciences, University of California, Irvine, Irvine, California, USA

Infection with (EBOV), a member of the family, causes a disease characterized by high levels of viremia, aberrant inflammation, coagulopathy, and lymphopenia. EBOV initially replicates in lymphoid tissues and disseminates via dendritic cells (DCs) and monocytes to liver, spleen, adrenal gland, and other secondary organs. EBOV protein VP35 is a critical immune evasion factor that inhibits type I interferon signaling and DC maturation. Read More

View Article and Full-Text PDF
February 2021

A Novel Subunit Vaccine Based on Outer Capsid Proteins of Grass Carp Reovirus (GCRV) Provides Protective Immunity against GCRV Infection in Rare Minnow ().

Pathogens 2020 Nov 13;9(11). Epub 2020 Nov 13.

Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China.

The grass carp hemorrhagic disease, caused by the grass carp reovirus (GCRV), has resulted in severe economic losses in the aquaculture industry in China. VP4 and VP35 are outer capsid proteins of GCRV and can induce an immune response in the host. Here, three recombinant baculoviruses, AcMNPV-VP35, AcMNPV-VP4, and AcMNPV-VP35-VP4, were generated to express recombinant VP4 and VP35 proteins from GCRV type II in insect cells by using the Bac-to-Bac baculovirus expression system to create a novel subunit vaccine. Read More

View Article and Full-Text PDF
November 2020

Piperine, an alkaloid of black pepper seeds can effectively inhibit the antiviral enzymes of Dengue and Ebola viruses, an in silico molecular docking study.

Virusdisease 2020 Sep 5;31(3):308-315. Epub 2020 Aug 5.

Department of Life Sciences, CHRIST (Deemed to be University), Bangalore, India.

Ebola and Dengue are the critical diseases caused by RNA viruses, especially in the tropical parts of the globe, including Asia and Africa, and no prominent therapeutic options are available so far. Here, an effort was made to evaluate the efficacy of black pepper ( L.) alkaloid Piperine as a potential drug through computational docking simulation. Read More

View Article and Full-Text PDF
September 2020

Ebola Virus VP35 Protein: Modeling of the Tetrameric Structure and an Analysis of Its Interaction with Human PKR.

J Proteome Res 2020 11 18;19(11):4533-4542. Epub 2020 Sep 18.

Department of Computer Science and Engineering, Indian Institute of Technology Kharagpur, West Bengal 721302, India.

The Viral Protein 35 (VP35), a crucial protein of the Zaire Ebolavirus (EBOV), interacts with a plethora of human proteins to cripple the human immune system. Despite its importance, the entire structure of the tetrameric assembly of EBOV VP35 and the means by which it antagonizes the autophosphorylation of the kinase domain of human protein kinase R (PKR) is still elusive. We consult existing structural information to model a tetrameric assembly of the VP35 protein where 93% of the protein is modeled using crystal structure templates. Read More

View Article and Full-Text PDF
November 2020

Ebola Virus Inclusion Body Formation and RNA Synthesis Are Controlled by a Novel Domain of Nucleoprotein Interacting with VP35.

J Virol 2020 07 30;94(16). Epub 2020 Jul 30.

Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, USA

Ebola virus (EBOV) inclusion bodies (IBs) are cytoplasmic sites of nucleocapsid formation and RNA replication, housing key steps in the virus life cycle that warrant further investigation. During infection, IBs display dynamic properties regarding their size and location. The contents of IBs also must transition prior to further viral maturation, assembly, and release, implying additional steps in IB function. Read More

View Article and Full-Text PDF

Impact of Měnglà Virus Proteins on Human and Bat Innate Immune Pathways.

J Virol 2020 06 16;94(13). Epub 2020 Jun 16.

Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA

Měnglà virus (MLAV), identified in bats, is a phylogenetically distinct member of the family Because the filoviruses Ebola virus (EBOV) and Marburg virus (MARV) modulate host innate immunity, MLAV VP35, VP40, and VP24 proteins were compared with their EBOV and MARV homologs for innate immune pathway modulation. In human and cells, MLAV VP35 behaved like EBOV and MARV VP35s, inhibiting virus-induced activation of the interferon beta (IFN-β) promoter and interferon regulatory factor 3 (IRF3) phosphorylation. MLAV VP35 also interacted with PACT, a host protein engaged by EBOV VP35 to inhibit RIG-I signaling. Read More

View Article and Full-Text PDF

Disorder-Order Transitions in Conformational Selection of a Peptide by Ebola Virus Nucleoprotein.

Authors:
Mark A Olson

ACS Omega 2020 Mar 13;5(11):5691-5697. Epub 2020 Mar 13.

Systems and Structural Biology Division, USAMRIID, Frederick, Maryland 21702, United States.

This study presents parallel-tempering lattice Monte Carlo simulations based on the side-chain-only (SICHO) model for calculating the conformational landscape of a 28-residue intrinsically disordered peptide extracted from the Ebola virus protein VP35. The central issue is the applicability of the SICHO potential energy function and in general coarse-grained (CG) representations of intermediate resolution for modeling large-scale conformational heterogeneity that includes both folded and unstructured peptide states. Crystallographic data shows that the peptide folds in a 4-helix-turn-3-helix topology upon complex formation with the Ebola virus nucleoprotein, whereas in isolation, the peptide transitions to a disordered conformational ensemble as observed in circular dichroism experiments. Read More

View Article and Full-Text PDF

The Integrity of the YxxL Motif of Ebola Virus VP24 Is Important for the Transport of Nucleocapsid-Like Structures and for the Regulation of Viral RNA Synthesis.

J Virol 2020 04 16;94(9). Epub 2020 Apr 16.

Institut für Virologie, Philipps-Universität Marburg, Marburg, Germany

While it is well appreciated that late domains in the viral matrix proteins are crucial to mediate efficient virus budding, little is known about roles of late domains in the viral nucleocapsid proteins. Here, we characterized the functional relevance of a YxxL motif with potential late-domain function in the Ebola virus nucleocapsid protein VP24. Mutations in the YxxL motif had two opposing effects on the functions of VP24. Read More

View Article and Full-Text PDF

Grass carp reovirus capsid protein interacts with cellular proteasome subunit beta-type 7: Evidence for the involvement of host proteasome during aquareovirus infection.

Fish Shellfish Immunol 2020 Mar 14;98:77-86. Epub 2019 Dec 14.

National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai, PR China. Electronic address:

The eukaryotic proteasome is a large multi-subunit complex that plays an important role in a wide range of fundamental cellular functions by degrading un-needed or damaged proteins, which also can be inverted or manipulated by viruses to favor viral infection. In this study, we demonstrated that proteasome subunit beta-type 7 (PSMB7), a proteasome-constitutive protein that is important for proteasome assembly, interacts with grass carp reovirus (GCRV) capsid proteins. Yeast 2-hybrid assay indicates that capsid protein VP38 of genotype Ⅲ GCRV could bind PSMB7, and this mutual interaction was further confirmed by pull-down, co-immunoprecipitation and subcellular co-localization assays. Read More

View Article and Full-Text PDF

Ebola virus replication is regulated by the phosphorylation of viral protein VP35.

Biochem Biophys Res Commun 2020 01 4;521(3):687-692. Epub 2019 Nov 4.

Beijing Institute of Biotechnology, 27 Taiping Rd, Haidian District, Beijing, 100850, PR China. Electronic address:

Ebola virus (EBOV) is a zoonotic pathogen, the infection often results in severe, potentially fatal, systematic disease in human and nonhuman primates. VP35, an essential viral RNA-dependent RNA polymerase cofactor, is indispensable for Ebola viral replication and host innate immune escape. In this study, VP35 was demonstrated to be phosphorylated at Serine/Threonine by immunoblotting, and the major phosphorylation sites was S187, S205, T206, S208 and S317 as revealed by LC-MS/MS. Read More

View Article and Full-Text PDF
January 2020

The LC8-RavP ensemble Structure Evinces A Role for LC8 in Regulating Lyssavirus Polymerase Functionality.

J Mol Biol 2019 12 18;431(24):4959-4977. Epub 2019 Oct 18.

From the Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA. Electronic address:

The rabies and Ebola viruses recruit the highly conserved host protein LC8 for their own reproductive success. In vivo knockouts of the LC8 recognition motif within the rabies virus phosphoprotein (RavP) result in completely nonlethal viral infections. In this work, we examine the molecular role LC8 plays in viral lethality. Read More

View Article and Full-Text PDF
December 2019

Regulation of the Ebola Virus VP24 Protein by SUMO.

J Virol 2019 12 12;94(1). Epub 2019 Dec 12.

Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain

Some viruses take advantage of conjugation of ubiquitin or ubiquitin-like proteins to enhance their own replication. One example is Ebola virus, which has evolved strategies to utilize these modification pathways to regulate the viral proteins VP40 and VP35 and to counteract the host defenses. Here, we show a novel mechanism by which Ebola virus exploits the ubiquitin and SUMO pathways. Read More

View Article and Full-Text PDF
December 2019

Global phosphoproteomic analysis of Ebola virions reveals a novel role for VP35 phosphorylation-dependent regulation of genome transcription.

Cell Mol Life Sci 2020 Jul 28;77(13):2579-2603. Epub 2019 Sep 28.

Center for Sickle Cell Disease, Howard University, 2201 Georgia Ave., N.W., Suite 321D, Washington, D.C., 20059, USA.

Ebola virus (EBOV) causes severe human disease with a high case fatality rate. The balance of evidence implies that the virus circulates in bats. The molecular basis for host-viral interactions, including the role for phosphorylation during infections, is largely undescribed. Read More

View Article and Full-Text PDF

A VP35 Mutant Ebola Virus Lacks Virulence but Can Elicit Protective Immunity to Wild-Type Virus Challenge.

Cell Rep 2019 09;28(12):3032-3046.e6

Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. Electronic address:

Zaire ebolavirus (EBOV) VP35 protein is a suppressor of type I interferon (IFN) production, an inhibitor of dendritic cell maturation, and a putative virulence determinant. Here, a recombinant EBOV encoding a mutant VP35 virus (VP35m) is demonstrated to activate RIG-I-like receptor signaling and innate antiviral pathways. When inoculated into cynomolgus macaques, VP35m exhibits dramatic attenuation as compared to wild-type EBOV (wtEBOV), with 20 or 300 times the standard 100% lethal challenge dose not causing EBOV disease (EVD). Read More

View Article and Full-Text PDF
September 2019

Intracellular human antibody fragments recognizing the VP35 protein of Zaire Ebola filovirus inhibit the protein activity.

BMC Biotechnol 2019 09 5;19(1):64. Epub 2019 Sep 5.

Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato SS554 09042 Monserrato, Cagliari, Italy.

Background: Ebola hemorrhagic fever is caused by the Ebola filovirus (EBOV), which is one of the most aggressive infectious agents known worldwide. The EBOV pathogenesis starts with uncontrolled viral replication and subversion of both the innate and adaptive host immune response. The multifunctional viral VP35 protein is involved in this process by exerting an antagonistic action against the early antiviral alpha/beta interferon (IFN-α/β) response, and represents a suitable target for the development of strategies to control EBOV infection. Read More

View Article and Full-Text PDF
September 2019

The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus.

iScience 2019 Sep 8;19:1279-1290. Epub 2019 Aug 8.

Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA; Infectious Disease Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address:

Here, we show that the US Food and Drug Administration-approved oral drug nitazoxanide (NTZ) broadly amplifies the host innate immune response to viruses and inhibits Ebola virus (EBOV) replication. We find that NTZ enhances retinoic-acid-inducible protein I (RIG-I)-like-receptor, mitochondrial antiviral signaling protein, interferon regulatory factor 3, and interferon activities and induces transcription of the antiviral phosphatase GADD34. NTZ significantly inhibits EBOV replication in human cells through its effects on RIG-I and protein kinase R (PKR), suggesting that it counteracts EBOV VP35 protein's ability to block RIG-I and PKR sensing of EBOV. Read More

View Article and Full-Text PDF
September 2019

Sudan Ebolavirus VP35-NP Crystal Structure Reveals a Potential Target for Pan-Filovirus Treatment.

mBio 2019 07 23;10(4). Epub 2019 Jul 23.

La Jolla Institute for Immunology, La Jolla, California, USA

The filoviruses are etiological agents of life-threatening hemorrhagic fever with high mortality rate and risk of potential outbreak. Among members of this family, the Ebola (EBOV), Sudan (SUDV), and Marburg (MARV) viruses are considered the most pathogenic for humans. The ebolavirus nucleoprotein (NP) is the most abundant protein in infected cells and is essential for viral transcription and replication; thus, it represents an attractive target for therapeutic intervention. Read More

View Article and Full-Text PDF

Inhibition of Marburg Virus RNA Synthesis by a Synthetic Anti-VP35 Antibody.

ACS Infect Dis 2019 08 4;5(8):1385-1396. Epub 2019 Jun 4.

Department of Medicine , Washington University School of Medicine , 660 South Euclid Avenue , St. Louis , Missouri 63110 , United States.

Marburg virus causes sporadic outbreaks of severe hemorrhagic fever with high case fatality rates. Approved, effective, and safe therapeutic or prophylactic countermeasures are lacking. To address this, we used phage display to engineer a synthetic antibody, sFab H3, which binds the Marburg virus VP35 protein (mVP35). Read More

View Article and Full-Text PDF

Ebola virus VP35 has novel NTPase and helicase-like activities.

Nucleic Acids Res 2019 06;47(11):5837-5851

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.

Ebola virus (EBOV) is a non-segmented, negative-sense RNA virus (NNSV) in the family Filoviridae, and is recognized as one of the most lethal pathogens in the planet. For RNA viruses, cellular or virus-encoded RNA helicases play pivotal roles in viral life cycles by remodelling viral RNA structures and/or unwinding viral dsRNA produced during replication. However, no helicase or helicase-like activity has ever been found to associate with any NNSV-encoded proteins, and it is unknown whether the replication of NNSVs requires the participation of any viral or cellular helicase. Read More

View Article and Full-Text PDF

Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics.

Analyst 2019 May 21;144(9):2881-2890. Epub 2019 Feb 21.

iHuman Institute, ShanghaiTech University, Shanghai 201210, China.

Although natural herbs have been a rich source of compounds for drug discovery, identification of bioactive components from natural herbs suffers from low efficiency and prohibitive cost of the conventional bioassay-based screening platforms. Here we develop a new strategy that integrates virtual screening, affinity mass spectrometry (MS) and targeted metabolomics for efficient discovery of herb-derived ligands towards a specific protein target site. Herb-based virtual screening conveniently selects herbs of potential bioactivity whereas affinity MS combined with targeted metabolomics readily screens candidate compounds in a high-throughput manner. Read More

View Article and Full-Text PDF

Contribution of Tomato torrado virus Vp26 coat protein subunit to systemic necrosis induction and virus infectivity in Solanum lycopersicum.

Virol J 2019 01 14;16(1). Epub 2019 Jan 14.

Department of Entomology, Animal Pests & Biotechnology, Institute of Plant Protection-National Research Institute, Władysława Węgorka 20 St, 60-318, Poznań, Poland.

Background: Tomato torrado virus (ToTV) infection manifests with burn-like symptoms on leaves, leaflets and upper stem parts of susceptible infected plants. The symptoms caused by ToTV may be considered as one of the most severe virus-induced forms of systemic necrosis, which spreads within the whole plant and leads to a lethal phenotype. However, to date there are no data revealing which viral genes encode for a specific pathogenicity determinant that triggers the plant necrotic response for any torradovirus. Read More

View Article and Full-Text PDF
January 2019

The Ebola Viral Protein 35 N-Terminus Is a Parallel Tetramer.

Biochemistry 2019 02 10;58(6):657-664. Epub 2019 Jan 10.

Department of Pathology and Immunology , Washington University School of Medicine in St. Louis , St. Louis , Missouri 63110 , United States.

Members of Mononegavirales, the order that includes nonsegmented negative sense RNA viruses (NNSVs), encode a small number of multifunctional proteins. In members of the Filoviridae family, virus protein 35 (VP35) facilitates immune evasion and functions as an obligatory cofactor for viral RNA synthesis. VP35 functions in a manner orthologous to that of phosphoproteins from other NNSVs. Read More

View Article and Full-Text PDF
February 2019

Virus and host interactions critical for filoviral RNA synthesis as therapeutic targets.

Antiviral Res 2019 02 11;162:90-100. Epub 2018 Dec 11.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Filoviruses, which include Ebola virus (EBOV) and Marburg virus, are negative-sense RNA viruses associated with sporadic outbreaks of severe viral hemorrhagic fever characterized by uncontrolled virus replication. The extreme virulence and emerging nature of these zoonotic pathogens make them a significant threat to human health. Replication of the filovirus genome and production of viral RNAs require the function of a complex of four viral proteins, the nucleoprotein (NP), viral protein 35 (VP35), viral protein 30 (VP30) and large protein (L). Read More

View Article and Full-Text PDF
February 2019

Structures of Ebola and Reston Virus VP35 Oligomerization Domains and Comparative Biophysical Characterization in All Ebolavirus Species.

Structure 2019 01 25;27(1):39-54.e6. Epub 2018 Oct 25.

The Max-Planck Institute of Biochemistry, Department of Molecular Structural Biology, Am Klopferspitz 18, 82152 Martinsried, Germany. Electronic address:

The multifunctional virion protein 35 (VP35) of ebolaviruses is a critical determinant of virulence and pathogenesis indispensable for viral replication and host innate immune evasion. Essential for VP35 function is homo-oligomerization via a coiled-coil motif. Here we report crystal structures of VP35 oligomerization domains from the prototypic Ebola virus (EBOV) and the non-pathogenic Reston virus (RESTV), together with a comparative biophysical characterization of the domains from all known species of the Ebolavirus genus. Read More

View Article and Full-Text PDF
January 2019

Insights into Ebola Virus VP35 and VP24 Interferon Inhibitory Functions and their Initial Exploitation as Drug Targets.

Infect Disord Drug Targets 2019 ;19(4):362-374

Department of Life and Environmental Sciences, University of Cagliari, Sardinia, Italy.

Upon viral infection, the interferon (IFN) system triggers potent antiviral mechanisms limiting viral growth and spread. Hence, to sustain their infection, viruses evolved efficient counteracting strategies to evade IFN control. Ebola virus (EBOV), member of the family Filoviridae, is one of the most virulent and deadly pathogen ever faced by humans. Read More

View Article and Full-Text PDF