| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Animal: RNA Viruses |
Centre for Biomolecular Sciences, School of Biology, Biomolecular Sciences Building, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK1
The University of Birmingham, The School of Chemistry, Edgbaston, Birmingham B15 2TT, UK2
Author for correspondence: Martin Ryan. Fax +44 1334 463400. e-mail martin.ryan{at}st-and.ac.uk
The 2A/2B cleavage of aphtho- and cardiovirus 2A polyproteins is mediated by their 2A proteins ‘cleaving’ at their own C termini. We have analysed this activity using artificial reporter polyprotein systems comprising green fluorescent protein (GFP) linked via foot-and-mouth disease virus (FMDV) 2A to 
-glucuronidase (GUS) – forming a single, long, open reading frame. Analysis of the distribution of radiolabel showed a high proportion of the in vitro translation products (
90%) were in the form of the ‘cleavage’ products GUS and [GFP2A]. Alternative models have been proposed to account for the ‘cleavage’ activity: proteolysis by a host-cell proteinase, autoproteolysis or a translational effect. To investigate the mechanism of this cleavage event constructs encoding site-directed mutant and naturally occurring ‘2A-like’ sequences were used to program in vitro translation systems and the gel profiles analysed. Analysis of site-directed mutant 2A sequences showed that ‘cleavage’ occurred in constructs in which all the candidate nucleophilic residues were substituted – with the exception of aspartate-12. This residue is not, however, conserved amongst all functional ‘2A-like’ sequences. ‘2A-like’ sequences were identified within insect virus polyproteins, the NS34 protein of type C rotaviruses, repeated sequences in Trypanosoma spp. and a eubacterial 
-glucosiduronasesequence(Thermatoga maritima aguA). All of the 2A-like sequences analysed were active (to various extents), other than the eubacterial -glucosiduronase 2A-like sequence. This method of control of protein biogenesis may well not, therefore, be confined to members of the Picornaviridae. Taken together, these data provide additional evidence that neither FMDV 2A nor ‘2A-like’ sequences are autoproteolytic elements.
This article has been cited by other articles:
|
|
 |
|
  Z. Lee, J. E. Dennis, and S. L. Gerson Imaging Stem Cell Implant for Cellular-Based Therapies Experimental Biology and Medicine, August 1, 2008; 233(8): 930 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Doronina, C. Wu, P. de Felipe, M. S. Sachs, M. D. Ryan, and J. D. Brown Site-Specific Release of Nascent Chains from Ribosomes at a Sense Codon Mol. Cell. Biol., July 1, 2008; 28(13): 4227 - 4239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Alli, P. Nguyen, and T. L. Geiger Retrogenic Modeling of Experimental Allergic Encephalomyelitis Associates T Cell Frequency but Not TCR Functional Affinity with Pathogenicity J. Immunol., July 1, 2008; 181(1): 136 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Luke, P. de Felipe, A. Lukashev, S. E. Kallioinen, E. A. Bruno, and M. D. Ryan Occurrence, function and evolutionary origins of '2A-like' sequences in virus genomes J. Gen. Virol., April 1, 2008; 89(4): 1036 - 1042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Sabatino Jr., J. Shires, J. D. Altman, M. L. Ford, and B. D. Evavold Loss of IFN-{gamma} Enables the Expansion of Autoreactive CD4+ T Cells to Induce Experimental Autoimmune Encephalomyelitis by a Nonencephalitogenic Myelin Variant Antigen J. Immunol., April 1, 2008; 180(7): 4451 - 4457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Moisini, P. Nguyen, L. Fugger, and T. L. Geiger Redirecting Therapeutic T Cells against Myelin-Specific T Lymphocytes Using a Humanized Myelin Basic Protein-HLA-DR2-{zeta} Chimeric Receptor J. Immunol., March 1, 2008; 180(5): 3601 - 3611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Funston, S. E. Kallioinen, P. de Felipe, M. D. Ryan, and R. D. Iggo Expression of heterologous genes in oncolytic adenoviruses using picornaviral 2A sequences that trigger ribosome skipping J. Gen. Virol., February 1, 2008; 89(2): 389 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Quintarelli, J. F. Vera, B. Savoldo, G. M. P. Giordano Attianese, M. Pule, A. E. Foster, H. E. Heslop, C. M. Rooney, M. K. Brenner, and G. Dotti Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes Blood, October 15, 2007; 110(8): 2793 - 2802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Atkins, N. M. Wills, G. Loughran, C.-Y. Wu, K. Parsawar, M. D. Ryan, C.-H. Wang, and C. C. Nelson A case for "StopGo": Reprogramming translation to augment codon meaning of GGN by promoting unconventional termination (Stop) after addition of glycine and then allowing continued translation (Go) RNA, June 1, 2007; 13(6): 803 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ziebuhr, B. Schelle, N. Karl, E. Minskaia, S. Bayer, S. G. Siddell, A. E. Gorbalenya, and V. Thiel Human Coronavirus 229E Papain-Like Proteases Have Overlapping Specificities but Distinct Functions in Viral Replication J. Virol., April 15, 2007; 81(8): 3922 - 3932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Nibert '2A-like' and 'shifty heptamer' motifs in penaeid shrimp infectious myonecrosis virus, a monosegmented double-stranded RNA virus J. Gen. Virol., April 1, 2007; 88(4): 1315 - 1318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-C. Kim, Y.-K. Kwon, S.-J. Joh, A. M. Lindberg, J.-H. Kwon, J.-H. Kim, and S.-J. Kim Molecular analysis of duck hepatitis virus type 1 reveals a novel lineage close to the genus Parechovirus in the family Picornaviridae. J. Gen. Virol., November 1, 2006; 87(Pt 11): 3307 - 3316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Carrillo, E. R. Tulman, G. Delhon, Z. Lu, A. Carreno, A. Vagnozzi, G. F. Kutish, and D. L. Rock Comparative Genomics of Foot-and-Mouth Disease Virus J. Virol., May 15, 2005; 79(10): 6487 - 6504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hertzig, E. Scandella, B. Schelle, J. Ziebuhr, S. G. Siddell, B. Ludewig, and V. Thiel Rapid identification of coronavirus replicase inhibitors using a selectable replicon RNA J. Gen. Virol., June 1, 2004; 85(6): 1717 - 1725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, J. Zhang, J. Lu, F. Yi, C. Liu, and Y. Hu Sequence analysis and genomic organization of a new insect picorna-like virus, Ectropis obliqua picorna-like virus, isolated from Ectropis obliqua J. Gen. Virol., May 1, 2004; 85(5): 1145 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. El Amrani, A. Barakate, B. M. Askari, X. Li, A. G. Roberts, M. D. Ryan, and C. Halpin Coordinate Expression and Independent Subcellular Targeting of Multiple Proteins from a Single Transgene Plant Physiology, May 1, 2004; 135(1): 16 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Grubman and B. Baxt Foot-and-Mouth Disease Clin. Microbiol. Rev., April 1, 2004; 17(2): 465 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Thomas, W. B. Klimstra, K. D. Ryman, and H. W. Heidner Sindbis Virus Vectors Designed To Express a Foreign Protein as a Cleavable Component of the Viral Structural Polyprotein J. Virol., May 15, 2003; 77(10): 5598 - 5606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Johansson, B. Niklasson, R. B. Tesh, D. R. Shafren, A. P. A. Travassos da Rosa, and A. M. Lindberg Molecular characterization of M1146, an American isolate of Ljungan virus (LV) reveals the presence of a new LV genotype J. Gen. Virol., April 1, 2003; 84(4): 837 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. de Felipe, L. E. Hughes, M. D. Ryan, and J. D. Brown Co-translational, Intraribosomal Cleavage of Polypeptides by the Foot-and-mouth Disease Virus 2A Peptide J. Biol. Chem., March 21, 2003; 278(13): 11441 - 11448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Schiedlmeier, H. Klump, E. Will, G. Arman-Kalcek, Z. Li, Z. Wang, A. Rimek, J. Friel, C. Baum, and W. Ostertag High-level ectopic HOXB4 expression confers a profound in vivo competitive growth advantage on human cord blood CD34+ cells, but impairs lymphomyeloid differentiation Blood, March 1, 2003; 101(5): 1759 - 1768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Neumann, M. A. Whitt, and Y. Kawaoka A decade after the generation of a negative-sense RNA virus from cloned cDNA - what have we learned? J. Gen. Virol., November 1, 2002; 83(11): 2635 - 2662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Johansson, B. Niklasson, J. Maizel, A. E. Gorbalenya, and A. M. Lindberg Molecular Analysis of Three Ljungan Virus Isolates Reveals a New, Close-to-Root Lineage of the Picornaviridae with a Cluster of Two Unrelated 2A Proteins J. Virol., July 29, 2002; 76(17): 8920 - 8930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. L. Donnelly, G. Luke, A. Mehrotra, X. Li, L. E. Hughes, D. Gani, and M. D. Ryan Analysis of the aphthovirus 2A/2B polyprotein 'cleavage' mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal 'skip' J. Gen. Virol., May 1, 2001; 82(5): 1013 - 1025. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
| J MED MICROBIOL | ALL SGM JOURNALS | |
