28
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Characterisation of cytoplasmic DNA complementary to non-retroviral RNA viruses in human cells

      research-article

      Read this article at

      Bookmark
          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

          The synthesis and subsequent genomic integration of DNA that is complementary to the genomes of non-retroviral RNA viruses are rarely observed. However, upon infection of various human cell lines and primary fibroblasts with the vesicular stomatitis virus (VSV), we detected DNA complementary to the VSV RNA. The VSV DNA was detected in the cytoplasm as single-stranded DNA fully complementary to the viral mRNA from the poly(A) region to the 7-methyl guanosine cap. The formation of this DNA was cell-dependent. Experimentally, we found that the transduction of cells that do not produce VSV DNA with the long interspersed nuclear element 1 and their infection with VSV could lead to the formation of VSV DNA. Viral DNA complementary to other RNA viruses was also detected in the respective infected human cells. Thus, the genetic information of the non-retroviral RNA virus genome can flow into the DNA of mammalian cells expressing LINE-1-like elements.

          Related collections

          Most cited references23

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

          Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition.

          R2 is a non-LTR retrotransposable element that inserts at a specific site in the 28S rRNA genes of most insects. We have expressed the open reading frame of the R2 element from Bombyx mori, R2Bm, in E. coli and shown that it encodes both sequence-specific endonuclease and reverse transcriptase activities. The R2 protein makes a specific nick in one of the DNA strands at the insertion site and uses the 3' hydroxyl group exposed by this nick to prime reverse transcription of its RNA transcript. After reverse transcription, cleavage of the second DNA strand occurs. A similar mechanism of insertion may be used by other non-LTR retrotransposable elements as well as short interspersed nucleotide elements.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Retrotransposons revisited: the restraint and rehabilitation of parasites.

            Retrotransposons, mainly LINEs, SINEs, and endogenous retroviruses, make up roughly 40% of the mammalian genome and have played an important role in genome evolution. Their prevalence in genomes reflects a delicate balance between their further expansion and the restraint imposed by the host. In any human genome only a small number of LINE1s (L1s) are active, moving their own and SINE sequences into new genomic locations and occasionally causing disease. Recent insights and new technologies promise answers to fundamental questions about the biology of transposable elements.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus.

              Interferons are circulating factors that bind to cell surface receptors, activating a signaling cascade, ultimately leading to both an antiviral response and an induction of growth inhibitory and/or apoptotic signals in normal and tumor cells. Attempts to exploit the ability of interferons to limit the growth of tumors in patients has met with limited results because of cancer-specific mutations of gene products in the interferon pathway. Although interferon-non-responsive cancer cells may have acquired a growth/survival advantage over their normal counterparts, they may have simultaneously compromised their antiviral response. To test this, we used vesicular stomatitis virus (VSV), an enveloped, negative-sense RNA virus exquisitely sensitive to treatment with interferon. VSV rapidly replicated in and selectively killed a variety of human tumor cell lines even in the presence of doses of interferon that completely protected normal human primary cell cultures. A single intratumoral injection of VSV was effective in reducing the tumor burden of nude mice bearing subcutaneous human melanoma xenografts. Our results support the use of VSV as a replication-competent oncolytic virus and demonstrate a new strategy for the treatment of interferon non-responsive tumors.
                Bookmark

                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                30 May 2014
                2014
                : 4
                : 5074
                Affiliations
                [1 ]Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine , Maebashi, Gunma 371-8511, JAPAN
                [2 ]Department of Dermatology, Gunma University Graduate School of Medicine , Maebashi, Gunma 371-8511, JAPAN
                [3 ]High Throughput Biology Centre, Johns Hopkins University School of Medicine , 733 N. Broadway/335 Broadway Research Building, Baltimore, Maryland, 21205, USA
                [4 ]MRC/UCL Centre for Medical Molecular Virology and Wohl Virion Centre, Division of Infection and Immunity, University College London , Gower Street, London WC1E 6BT, United Kingdom
                Author notes
                Article
                srep05074
                10.1038/srep05074
                4038843
                24875540
                19820f49-439c-4811-82e8-fb0e7f6c253d
                Copyright © 2014, Macmillan Publishers Limited. All rights reserved

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images in this article are included in the article's Creative Commons license, unless indicated otherwise in the image credit; if the image is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the image. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                : 20 November 2013
                : 02 May 2014
                Categories
                Article

                Uncategorized
                Uncategorized

                Comments

                Comment on this article