This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yu, H.
Right arrow Articles by Behrens, S.-E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yu, H.
Right arrow Articles by Behrens, S.-E.

 Previous Article  |  Next Article 

Journal of Virology, May 1999, p. 3638-3648, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Sequence and Structural Elements at the 3' Terminus of Bovine Viral Diarrhea Virus Genomic RNA: Functional Role during RNA Replication

Haiying Yu, Claus W. Grassmann, and Sven-Erik Behrens*

Institut für Virologie (FB Veterinärmedizin), Justus-Liebig-Universität Giessen, D-35392 Giessen, Germany

Received 18 September 1998/Accepted 19 January 1999

Bovine viral diarrhea virus (BVDV), a member of the genus Pestivirus in the family Flaviviridae, has a positive-stranded RNA genome consisting of a single open reading frame and untranslated regions (UTRs) at the 5' and 3' ends. Computer modeling suggested the 3' UTR comprised single-stranded regions as well as stem-loop structures---features that were suspected of being essentially implicated in the viral RNA replication pathway. Employing a subgenomic BVDV RNA (DI9c) that was shown to function as an autonomous RNA replicon (S.-E. Behrens, C. W. Grassmann, H. J. Thiel, G. Meyers, and N. Tautz, J. Virol. 72:2364-2372, 1998) the goal of this study was to determine the RNA secondary structure of the 3' UTR by experimental means and to investigate the significance of defined RNA motifs for the RNA replication pathway. Enzymatic and chemical structure probing revealed mainly the conserved terminal part (termed 3'C) of the DI9c 3' UTR containing distinctive RNA motifs, i.e., a stable stem-loop, SL I, near the RNA 3' terminus and a considerably less stable stem-loop, SL II, that forms the 5' portion of 3'C. SL I and SL II are separated by a long single-stranded intervening sequence, denoted SS. The 3'-terminal four C residues of the viral RNA were confirmed to be single stranded as well. Other intramolecular interactions, e.g., with upstream DI9c RNA sequences, were not detected under the experimental conditions used. Mutagenesis of the DI9c RNA demonstrated that the SL I and SS motifs do indeed play essential roles during RNA replication. Abolition of RNA stems, which ought to maintain the overall folding of SL I, as well as substitution of certain single-stranded nucleotides located in the SS region or SL I loop region, gave rise to DI9c derivatives unable to replicate. Conversely, SL I stems comprising compensatory base exchanges turned out to support replication, but mostly to a lower degree than the original structure. Surprisingly, replacement of a number of residues, although they were previously defined as constituents of a highly conserved stretch of sequence of the SS motif, had little effect on the replication ability of DI9c. In summary, these results indicate that RNA structure as well as sequence elements harbored within the 3'C region of the BVDV 3' UTR create a common cis-acting element of the replication process. The data further point at possible interaction sites of host and/or viral proteins and thus provide valuable information for future experiments intended to identify and characterize these factors.

* Corresponding author. Mailing address: Institut für Virologie (FB Veterinärmedizin), Justus-Liebig-Universität Giessen, Frankfurter Str. 107, D-35392 Giessen, Germany. Phone: 496419938350. Fax: 496419938359. E-mail: Sven-Erik.Behrens{at}vetmed.uni-giessen.de.

Journal of Virology, May 1999, p. 3638-3648, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Xiao, M., Wang, Y., Zhu, Z., Yu, J., Wan, L., Chen, J. (2009). Influence of NS5A protein of classical swine fever virus (CSFV) on CSFV internal ribosome entry site-dependent translation. J. Gen. Virol. 90: 2923-2928 [Abstract] [Full Text]  
  • Wegelt, A., Reimann, I., Zemke, J., Beer, M. (2009). New insights into processing of bovine viral diarrhea virus glycoproteins Erns and E1. J. Gen. Virol. 90: 2462-2467 [Abstract] [Full Text]  
  • Enterlein, S., Schmidt, K. M., Schumann, M., Conrad, D., Krahling, V., Olejnik, J., Muhlberger, E. (2009). The Marburg Virus 3' Noncoding Region Structurally and Functionally Differs from That of Ebola Virus. J. Virol. 83: 4508-4519 [Abstract] [Full Text]  
  • Simmonds, P., Karakasiliotis, I., Bailey, D., Chaudhry, Y., Evans, D. J., Goodfellow, I. G. (2008). Bioinformatic and functional analysis of RNA secondary structure elements among different genera of human and animal caliciviruses. Nucleic Acids Res 36: 2530-2546 [Abstract] [Full Text]  
  • Xiao, M., Bai, Y., Xu, H., Geng, X., Chen, J., Wang, Y., Chen, J., Li, B. (2008). Effect of NS3 and NS5B proteins on classical swine fever virus internal ribosome entry site-mediated translation and its host cellular translation. J. Gen. Virol. 89: 994-999 [Abstract] [Full Text]  
  • Isken, O., Baroth, M., Grassmann, C. W., Weinlich, S., Ostareck, D. H., Ostareck-Lederer, A., Behrens, S.-E. (2007). Nuclear factors are involved in hepatitis C virus RNA replication. RNA 13: 1675-1692 [Abstract] [Full Text]  
  • Song, Y., Friebe, P., Tzima, E., Junemann, C., Bartenschlager, R., Niepmann, M. (2006). The Hepatitis C Virus RNA 3'-Untranslated Region Strongly Enhances Translation Directed by the Internal Ribosome Entry Site. J. Virol. 80: 11579-11588 [Abstract] [Full Text]  
  • Xiao, M., Li, H., Wang, Y., Wang, X., Wang, W., Peng, J., Chen, J., Li, B. (2006). Characterization of the N-terminal domain of classical swine fever virus RNA-dependent RNA polymerase. J. Gen. Virol. 87: 347-356 [Abstract] [Full Text]  
  • Weik, M., Enterlein, S., Schlenz, K., Muhlberger, E. (2005). The Ebola Virus Genomic Replication Promoter Is Bipartite and Follows the Rule of Six. J. Virol. 79: 10660-10671 [Abstract] [Full Text]  
  • Pankraz, A., Thiel, H.-J., Becher, P. (2005). Essential and Nonessential Elements in the 3' Nontranslated Region of Bovine Viral Diarrhea Virus. J. Virol. 79: 9119-9127 [Abstract] [Full Text]  
  • Sosnovtsev, S. V., Belliot, G., Chang, K.-O., Onwudiwe, O., Green, K. Y. (2005). Feline Calicivirus VP2 Is Essential for the Production of Infectious Virions. J. Virol. 79: 4012-4024 [Abstract] [Full Text]  
  • ISKEN, O., GRASSMANN, C. W., YU, H., BEHRENS, S.-E. (2004). Complex signals in the genomic 3' nontranslated region of bovine viral diarrhea virus coordinate translation and replication of the viral RNA. RNA 10: 1637-1652 [Abstract] [Full Text]  
  • Thurner, C., Witwer, C., Hofacker, I. L., Stadler, P. F. (2004). Conserved RNA secondary structures in Flaviviridae genomes. J. Gen. Virol. 85: 1113-1124 [Abstract] [Full Text]  
  • Boot, H. J., Pritz-Verschuren, S. B. E. (2004). Modifications of the 3'-UTR stem-loop of infectious bursal disease virus are allowed without influencing replication or virulence. Nucleic Acids Res 32: 211-222 [Abstract] [Full Text]  
  • Khromykh, A. A, Kondratieva, N., Sgro, J.-Y., Palmenberg, A., Westaway, E. G (2003). Significance in Replication of the Terminal Nucleotides of the Flavivirus Genome. J. Virol. 77: 10623-10629 [Abstract] [Full Text]  
  • Yi, M., Lemon, S. M. (2003). 3' Nontranslated RNA Signals Required for Replication of Hepatitis C Virus RNA. J. Virol. 77: 3557-3568 [Abstract] [Full Text]  
  • Weik, M., Modrof, J., Klenk, H.-D., Becker, S., Muhlberger, E. (2002). Ebola Virus VP30-Mediated Transcription Is Regulated by RNA Secondary Structure Formation. J. Virol. 76: 8532-8539 [Abstract] [Full Text]  
  • Meyer, C., von Freyburg, M., Elbers, K., Meyers, G. (2002). Recovery of Virulent and RNase-Negative Attenuated Type 2 Bovine Viral Diarrhea Viruses from Infectious cDNA Clones. J. Virol. 76: 8494-8503 [Abstract] [Full Text]  
  • De Tomassi, A., Pizzuti, M., Graziani, R., Sbardellati, A., Altamura, S., Paonessa, G., Traboni, C. (2002). Cell Clones Selected from the Huh7 Human Hepatoma Cell Line Support Efficient Replication of a Subgenomic GB Virus B Replicon. J. Virol. 76: 7736-7746 [Abstract] [Full Text]  
  • Friebe, P., Bartenschlager, R. (2002). Genetic Analysis of Sequences in the 3' Nontranslated Region of Hepatitis C Virus That Are Important for RNA Replication. J. Virol. 76: 5326-5338 [Abstract] [Full Text]  
  • Grassmann, C. W., Isken, O., Tautz, N., Behrens, S.-E. (2001). Genetic Analysis of the Pestivirus Nonstructural Coding Region: Defects in the NS5A Unit Can Be Complemented in trans. J. Virol. 75: 7791-7802 [Abstract] [Full Text]  
  • Cuceanu, N. M., Tuplin, A., Simmonds, P. (2001). Evolutionarily conserved RNA secondary structures in coding and non-coding sequences at the 3' end of the hepatitis G virus/GB-virus C genome. J. Gen. Virol. 82: 713-722 [Abstract] [Full Text]  
  • KIEFT, J.S., GRECH, A., ADAMS, P., DOUDNA, J.A. (2001). Mechanisms of Internal Ribosome Entry in Translation Initiation. Cold Spring Harb Symp Quant Biol 66: 277-284 [Abstract]  
  • Becher, P., Orlich, M., Thiel, H.-J. (2000). Mutations in the 5' Nontranslated Region of Bovine Viral Diarrhea Virus Result in Altered Growth Characteristics. J. Virol. 74: 7884-7894 [Abstract] [Full Text]  
  • Yu, H., Isken, O., Grassmann, C. W., Behrens, S.-E. (2000). A Stem-Loop Motif Formed by the Immediate 5' Terminus of the Bovine Viral Diarrhea Virus Genome Modulates Translation as well as Replication of the Viral RNA. J. Virol. 74: 5825-5835 [Abstract] [Full Text]  
  • Gu, B., Liu, C., Lin-Goerke, J., Maley, D. R., Gutshall, L. L., Feltenberger, C. A., Del Vecchio, A. M. (2000). The RNA Helicase and Nucleotide Triphosphatase Activities of the Bovine Viral Diarrhea Virus NS3 Protein Are Essential for Viral Replication. J. Virol. 74: 1794-1800 [Abstract] [Full Text]  
  • Grassmann, C. W., Isken, O., Behrens, S.-E. (1999). Assignment of the Multifunctional NS3 Protein of Bovine Viral Diarrhea Virus during RNA Replication: an In Vivo and In Vitro Study. J. Virol. 73: 9196-9205 [Abstract] [Full Text]  
  • Steffens, S., Thiel, H.-J., Behrens, S.-E. (1999). The RNA-dependent RNA polymerases of different members of the family Flaviviridae exhibit similar properties in vitro. J. Gen. Virol. 80: 2583-2590 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»