81 results match your criteria vp35 peptides

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

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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

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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

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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

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December 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

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September 2019

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

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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

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February 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

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Transcriptomics Reveal Antiviral Gene Induction in the Egyptian Rousette Bat Is Antagonized In Vitro by Marburg Virus Infection.

Viruses 2018 11 2;10(11). Epub 2018 Nov 2.

Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.

The Egyptian rousette bat (ERB) is the only known Marburg virus (MARV) reservoir host. ERBs develop a productive MARV infection with low viremia and shedding but no overt disease, suggesting this virus is efficiently controlled by ERB antiviral responses. This dynamic would contrast with humans, where MARV-mediated interferon (IFN) antagonism early in infection is thought to contribute to the severe, often fatal disease. Read More

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November 2018

Conservation of Structure and Immune Antagonist Functions of Filoviral VP35 Homologs Present in Microbat Genomes.

Cell Rep 2018 07;24(4):861-872.e6

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

Non-retroviral integrated RNA viral sequences (NIRVs) potentially encoding ∼280 amino acid homologs to filovirus VP35 proteins are present across the Myotis genus of bats. These are estimated to have been maintained for ∼18 million years, indicating their co-option. To address the reasons for co-option, 16 Myotis VP35s were characterized in comparison to VP35s from the extant filoviruses Ebola virus and Marburg virus, in which VP35s play critical roles in immune evasion and RNA synthesis. Read More

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Plasmid pcDNA3.1-s11 constructed based on the S11 segment of grass carp reovirus as DNA vaccine provides immune protection.

Vaccine 2018 06;36(25):3613-3621

College of Fisheries, Henan Normal University, Xinxiang, China. Electronic address:

Although some commercial vaccines against grass carp reovirus (GCRV) are available, given the many varieties of GCRV and limited types of vaccines, the disease caused by GCRV remains a major problem, which leads to economic losses in grass carp aquaculture. A reovirus strain (GCRV-HN14) was recently isolated from local diseased fish in our laboratory. The S11 segment of GCRV-HN14 was speculated to encode the virus capsid protein VP35. Read More

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Human transbodies that interfere with the functions of Ebola virus VP35 protein in genome replication and transcription and innate immune antagonism.

Emerg Microbes Infect 2018 Mar 21;7(1):41. Epub 2018 Mar 21.

Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.

Small molecular inhibitors and passive immunization against Ebola virus disease (EVD) have been tested in animal models, including rodents and non-human primates, as well as in clinical trials. Nevertheless, there is currently no Food and Drug Administration (FDA)-approved therapy, and alternative strategies must be pursued. The aim of this study was to produce cell-penetrable human single-chain antibodies (transbodies) that are able to interfere with the activities of interferon inhibitory domain (IID) of the VP35 protein, a multifunctional virulence factor of Ebola virus (EBOV). Read More

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Parallel Tempering of Dark Matter from the Ebola Virus Proteome: Comparison of CHARMM36m and CHARMM22 Force Fields with Implicit Solvent.

Mark A Olson

J Chem Inf Model 2018 01 15;58(1):111-118. Epub 2017 Dec 15.

Molecular and Translational Sciences, USAMRIID , Frederick, Maryland 21702, United States.

Intrinsically disordered proteins are characterized by their large manifold of thermally accessible conformations and their related statistical weights, making them an interesting target of simulation studies. To assess the development of a computational framework for modeling this distinct class of proteins, this work examines temperature-based replica-exchange simulations to generate a conformational ensemble of a 28-residue peptide from the Ebola virus protein VP35. Starting from a prefolded helix-β-turn-helix topology observed in a crystallographic assembly, the simulation strategy tested is the recently refined CHARMM36m force field combined with a generalized Born solvent model. Read More

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January 2018

Ebolavirus interferon antagonists-protein interaction perspectives to combat pathogenesis.

Brief Funct Genomics 2018 11;17(6):392-401

Department of Computer Science and Engineering, IIT Kharagpur, India.

Zaire ebolavirus, one of the most pathogenic species of Ebolavirus, is a significant threat to the human community being both highly infectious and lethal. The viral proteins (VPs), specifically VP24 and VP35, antagonize the interferon (IFN) proteins accountable for human immune response. Several efforts have been made to design vaccines and therapeutics drugs. Read More

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November 2018

Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor.

PLoS One 2017 17;12(10):e0186450. Epub 2017 Oct 17.

Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.

It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. Read More

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October 2017

The Ebola virus VP35 protein binds viral immunostimulatory and host RNAs identified through deep sequencing.

PLoS One 2017 21;12(6):e0178717. Epub 2017 Jun 21.

Virology Group, J. Craig Venter Institute, Rockville, Maryland, United States of America.

Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN) response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV), and this IFN-antagonist activity is directly correlated with its ability to bind RNA. Read More

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October 2017

Assays to Measure Suppression of Type I Interferon Responses by Filovirus VP35 Proteins.

Methods Mol Biol 2017 ;1628:133-142

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

Innate immunity is the first line of defense against virus infections and is marked by production of type I interferons (IFN), a family of cytokines that includes IFN-β and several IFN-αs. For the filoviruses and many other RNA viruses that replicate in the cytoplasm, the RIG-I-like pattern recognition receptors (RLRs) are potential triggers of IFN production. To counteract such innate antiviral responses, many viruses encode proteins that antagonize RLR signaling. Read More

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Topoisomerase II Inhibitors Induce DNA Damage-Dependent Interferon Responses Circumventing Ebola Virus Immune Evasion.

mBio 2017 04 4;8(2). Epub 2017 Apr 4.

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

Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. Read More

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A simulation investigation on interaction mechanism between Ebola nucleoprotein and VP35 peptide.

J Biomol Struct Dyn 2018 Mar 10;36(4):1009-1028. Epub 2017 Apr 10.

a National Synchrotron Radiation Laboratory , University of Science and Technology of China , Hefei 230029 , People's Republic of China.

Ebola viruses (EBOV) will induce acute hemorrhagic fever, which is fatal to humans and nonhuman primates. The combination of EBOV VP35 peptide with nucleoprotein N-terminal (NPNTD) is proposed based on static crystal structures in recent studies, but VP35 binding mechanism and conformational dynamics are still unclear. This investigation, using Molecular Dynamic (MD) simulation and Molecular Mechanics Generalized Born Surface Area (MM-GB/SA) energy calculation, more convincingly proves the greater roles of the protein binding mechanisms than do hints from the static crystal structure observations. Read More

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Innate Immune Responses of Bat and Human Cells to Filoviruses: Commonalities and Distinctions.

J Virol 2017 04 29;91(8). Epub 2017 Mar 29.

Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA

Marburg (MARV) and Ebola (EBOV) viruses are zoonotic pathogens that cause severe hemorrhagic fever in humans. The natural reservoir of MARV is the Egyptian rousette bat (); that of EBOV is unknown but believed to be another bat species. The Egyptian rousette develops subclinical productive infection with MARV but is refractory to EBOV. Read More

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Novel activities by ebolavirus and marburgvirus interferon antagonists revealed using a standardized in vitro reporter system.

Virology 2017 01 6;501:147-165. Epub 2016 Dec 6.

Viral Special Pathogens Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States. Electronic address:

Filoviruses are highly lethal in humans and nonhuman primates, likely due to potent antagonism of host interferon (IFN) responses early in infection. Filoviral protein VP35 is implicated as the major IFN induction antagonist, while Ebola virus (EBOV) VP24 or Marburg virus (MARV) VP40 are known to block downstream IFN signaling. Despite progress elucidating EBOV and MARV antagonist function, those for most other filoviruses, including Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV), Bundibugyo (BDBV) and Ravn (RAVV) viruses, remain largely neglected. Read More

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January 2017

The Ebola Interferon Inhibiting Domains Attenuate and Dysregulate Cell-Mediated Immune Responses.

PLoS Pathog 2016 Dec 8;12(12):e1006031. Epub 2016 Dec 8.

Department of Pathology, the University of Texas Medical Branch, Galveston, Texas, United States of America.

Ebola virus (EBOV) infections are characterized by deficient T-lymphocyte responses, T-lymphocyte apoptosis and lymphopenia. We previously showed that disabling of interferon-inhibiting domains (IIDs) in the VP24 and VP35 proteins effectively unblocks maturation of dendritic cells (DCs) and increases the secretion of cytokines and chemokines. Here, we investigated the role of IIDs in adaptive and innate cell-mediated responses using recombinant viruses carrying point mutations, which disabled IIDs in VP24 (EBOV/VP24m), VP35 (EBOV/VP35m) or both (EBOV/VP35m/VP24m). Read More

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December 2016

Ebola virus: A gap in drug design and discovery - experimental and computational perspective.

Chem Biol Drug Des 2017 03 31;89(3):297-308. Epub 2016 Oct 31.

Molecular Modeling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.

The Ebola virus, formally known as the Ebola hemorrhagic fever, is an acute viral syndrome causing sporadic outbreaks that have ravaged West Africa. Due to its extreme virulence and highly transmissible nature, Ebola has been classified as a category A bioweapon organism. Only recently have vaccine or drug regimens for the Ebola virus been developed, including Zmapp and peptides. Read More

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Effects of Filovirus Interferon Antagonists on Responses of Human Monocyte-Derived Dendritic Cells to RNA Virus Infection.

J Virol 2016 05 29;90(10):5108-5118. Epub 2016 Apr 29.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

Unlabelled: Dendritic cells (DCs) are major targets of filovirus infection in vivo Previous studies have shown that the filoviruses Ebola virus (EBOV) and Marburg virus (MARV) suppress DC maturation in vitro Both viruses also encode innate immune evasion functions. The EBOV VP35 (eVP35) and the MARV VP35 (mVP35) proteins each can block RIG-I-like receptor signaling and alpha/beta interferon (IFN-α/β) production. The EBOV VP24 (eVP24) and MARV VP40 (mVP40) proteins each inhibit the production of IFN-stimulated genes (ISGs) by blocking Jak-STAT signaling; however, this occurs by different mechanisms, with eVP24 blocking nuclear import of tyrosine-phosphorylated STAT1 and mVP40 blocking Jak1 function. Read More

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Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins.

Cell Rep 2016 Feb 11;14(7):1632-1640. Epub 2016 Feb 11.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

Suppression of innate immune responses during filoviral infection contributes to disease severity. Ebola (EBOV) and Marburg (MARV) viruses each encode a VP35 protein that suppresses RIG-I-like receptor signaling and interferon-α/β (IFN-α/β) production by several mechanisms, including direct binding to double stranded RNA (dsRNA). Here, we demonstrate that in cell culture, MARV infection results in a greater upregulation of IFN responses as compared to EBOV infection. Read More

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February 2016

Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus.

Nat Rev Microbiol 2015 Nov 6;13(11):663-76. Epub 2015 Oct 6.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. Read More

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November 2015

Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells.

Virology 2015 Nov 6;485:145-52. Epub 2015 Aug 6.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States. Electronic address:

Lloviu virus (LLOV) is a new member of the filovirus family that also includes Ebola virus (EBOV) and Marburg virus (MARV). LLOV has not been cultured; however, its genomic RNA sequence indicates the coding capacity to produce homologs of the EBOV and MARV VP24, VP35, and VP40 proteins. EBOV and MARV VP35 proteins inhibit interferon (IFN)-alpha/beta production and EBOV VP35 blocks activation of the antiviral kinase PKR. Read More

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November 2015

Assessing the contribution of interferon antagonism to the virulence of West African Ebola viruses.

Nat Commun 2015 Aug 5;6:8000. Epub 2015 Aug 5.

Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, Montana 59840, USA.

The current Ebola virus (EBOV) outbreak in West Africa is unprecedented in terms of both its size and duration, and there has been speculation and concern regarding the potential for EBOV to increase in virulence as a result of its prolonged circulation in humans. Here we investigate the relative potency of the interferon (IFN) inhibitors encoded by EBOVs from West Africa, since an important EBOV virulence factor is inhibition of the antiviral IFN response. Based on this work we show that, in terms of IFN antagonism, the West African viruses display no discernible differences from the prototype Mayinga isolate, which corroborates epidemiological data suggesting these viruses show no increased virulence compared with those from previous outbreaks. Read More

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Different Temporal Effects of Ebola Virus VP35 and VP24 Proteins on Global Gene Expression in Human Dendritic Cells.

J Virol 2015 Aug 13;89(15):7567-83. Epub 2015 May 13.

Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA Department of Microbiology & Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, Texas, USA

Unlabelled: Ebola virus (EBOV) causes a severe hemorrhagic fever with a deficient immune response, lymphopenia, and lymphocyte apoptosis. Dendritic cells (DC), which trigger the adaptive response, do not mature despite EBOV infection. We recently demonstrated that DC maturation is unblocked by disabling the innate response antagonizing domains (IRADs) in EBOV VP35 and VP24 by the mutations R312A and K142A, respectively. Read More

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