For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
10
views
52
references
 Top references
cited by
14
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      393
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Dengue Virus Reporter Replicon is a Valuable Tool for Antiviral Drug Discovery and Analysis of Virus Replication Mechanisms

      review-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (DENV), a member of the Flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. However, no specific antiviral drug or licensed vaccine currently targets DENV infection. The replicon system has all the factors needed for viral replication in cells. Since the development of replicon systems, transient and stable reporter replicons, as well as reporter viruses, have been used in the study of various virological aspects of DENV and in the identification of DENV inhibitors. In this review, we summarize the DENV reporter replicon system and its applications in high-throughput screening (HTS) for identification of anti-DENV inhibitors. We also describe the use of this system in elucidation of the mechanisms of virus replication and viral dynamics in vivo and in vitro.

          Related collections

          Most cited references52

          • Record: found
          • Abstract: found
          • Article: not found

          Composition and Three-Dimensional Architecture of the Dengue Virus Replication and Assembly Sites

          Sonja Welsch, Sven Miller, Inés Romero-Brey … (2009)
          Summary Positive-strand RNA viruses are known to rearrange cellular membranes to facilitate viral genome replication. The biogenesis and three-dimensional organization of these membranes and the link between replication and virus assembly sites is not fully clear. Using electron microscopy, we find Dengue virus (DENV)-induced vesicles, convoluted membranes, and virus particles to be endoplasmic reticulum (ER)-derived, and we detect double-stranded RNA, a presumed marker of RNA replication, inside virus-induced vesicles. Electron tomography (ET) shows DENV-induced membrane structures to be part of one ER-derived network. Furthermore, ET reveals vesicle pores that could enable release of newly synthesized viral RNA and reveals budding of DENV particles on ER membranes directly apposed to vesicle pores. Thus, DENV modifies ER membrane structure to promote replication and efficient encapsidation of the genome into progeny virus. This architecture of DENV replication and assembly sites could explain the coordination of distinct steps of the flavivirus replication cycle.
          Article 0 comments Cited 451 times – based on 0 reviews     Review now
            • Record: found
            • Abstract: found
            • Article: not found

            Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo.

            Bakhos A Tannous, Dong-Eog Kim, Juliet L Fernandez … (2005)
            Photoproteins have played a major role in advancing our understanding of biological processes. A broader array of biocompatible, nontoxic, and novel reporters can serve to expand this potential. Here we describe the properties of a luciferase from the copepod marine organism Gaussia princeps. It is a monomeric protein composed of 185 aa (19.9 kDa) with a short coding sequence (555 bp) making it suitable for viral vectors. The humanized form of Gaussia luciferase (hGLuc) was efficiently expressed in mammalian cells following delivery by HSV-1 amplicon vectors. It was found to be nontoxic and naturally secreted, with flash bioluminescence characteristics similar to those of other coelenterazine luciferases. hGLuc generated over 1000-fold higher bioluminescent signal intensity from live cells together with their immediate environment and over 100-fold higher intensity from viable cells alone (not including secreted luciferase) or cell lysates, compared to humanized forms of firefly (hFLuc) and Renilla (hRLuc) luciferases expressed under similar conditions. Furthermore, hGLuc showed 200-fold higher signal intensity than hRLuc and intensity comparable to that of hFLuc in vivo under standard imaging conditions. Gaussia luciferase provides a sensitive means of imaging gene delivery and other events in living cells in culture and in vivo, with a unique combination of features including high signal intensity, secretion, and ATP independence, thus being able to report from the cells and their environment in real time.
            Article 0 comments Cited 184 times – based on 0 reviews     Review now
              • Record: found
              • Abstract: found
              • Article: not found

              Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease.

              Raphaël M. Zellweger, Tyler R. Prestwood, Sujan Shresta (2010)
              Dengue virus (DENV) causes disease ranging from dengue fever (DF), a self-limited febrile illness, to the potentially lethal dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). DHF/DSS usually occurs in patients who have acquired DENV-reactive antibodies prior to infection, either from a previous infection with a heterologous DENV serotype or from an immune mother. Hence, it has been hypothesized that subneutralizing levels of antibodies exacerbate disease, a phenomenon termed antibody-dependent enhancement (ADE). However, given the lack of suitable animal models for DENV infection, the mechanism of ADE and its contribution to pathology remain elusive. Here we demonstrate in mice that DENV-specific antibodies can sufficiently increase severity of disease so that a mostly nonlethal illness becomes a fatal disease resembling human DHF/DSS. Antibodies promote massive infection of liver sinusoidal endothelial cells (LSECs), resulting in increased systemic levels of virus. Thus, a subprotective humoral response may, under some circumstances, have pathological consequences. 2010 Elsevier Inc. All rights reserved.
              Article 0 comments Cited 146 times – based on 0 reviews     Review now
                All references

                Author and article information

                Contributors
                Luis Martinez-Sobrido: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Viruses
                Journal ID (iso-abbrev): Viruses
                Journal ID (publisher-id): viruses
                Title: Viruses
                Publisher: MDPI
                ISSN (Electronic): 1999-4915
                Publication date (Electronic): 05 May 2016
                Publication date Collection: May 2016
                Volume: 8
                Issue: 5
                Electronic Location Identifier: 122
                Affiliations
                [1 ]Department of Virology 1, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; fumihiro@ 123456nih.go.jp
                [2 ]Viral Infectious Diseases Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
                Author notes
                [* ]Correspondence: hishiki-tk@ 123456igakuken.or.jp ; Tel.: +81-3-5316-3225 (ext. 2721); Fax: +81-3-5316-3137
                Article
                Publisher ID: viruses-08-00122
                DOI: 10.3390/v8050122
                PMC ID: 4885077
                PubMed ID: 27164125
                SO-VID: 9e633c50-a2e2-4241-a191-6264fe83de45
                Copyright © © 2016 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 29 March 2016
                Date accepted : 26 April 2016
                Categories
                Subject: Review

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: dengue virus,flavivirus,reporter replicon,replication,antiviral drug,high-throughput screening
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: dengue virus, flavivirus, reporter replicon, replication, antiviral drug, high-throughput screening

                Comments

                Comment on this article

                Related Documents Log
                scite_

                Similar content393

                See all similar

                Cited by14

                See all cited by

                Most referenced authors996

                See all reference authors