This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Guan, Y.
Right arrow Articles by Wainberg, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guan, Y.
Right arrow Articles by Wainberg, M. A.

 Previous Article  |  Next Article 

Journal of Virology, March 2001, p. 2776-2785, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2776-2785.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Novel, Live Attenuated Simian Immunodeficiency Virus Constructs Containing Major Deletions in Leader RNA Sequences

Yongjun Guan,1,2 James B. Whitney,1,3 Chen Liang,1,2 and Mark A. Wainberg1,2,3,*

McGill University AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2,1 and Department of Medicine2 and Department of Microbiology and Immunology,3 McGill University, Montreal, Quebec, Canada H3A 2B4

Received 14 August 2000/Accepted 20 December 2000

We have constructed a series of simian immunodeficiency virus (SIV) mutants containing deletions within a 97-nucleotide (nt) region of the leader sequence. Deletions in this region markedly decreased the replication capacity in tissue culture, i.e., in both the C8166 and CEMx174 cell lines, as well as in rhesus macaque peripheral blood mononuclear cells. In addition, these deletions adversely affected the packaging of viral genomic RNA into virions, the processing of Gag precursor proteins, and patterns of viral proteins in virions, as assessed by biochemical labeling and polyacrylamide gel electrophoresis. Different levels of attenuation were achieved by varying the size and position of deletions within this 97-nt region, and among a series of constructs that were generated, it was possible to rank in vitro virulence relative to that of wild-type virus. In all of these cases, the most severe impact on viral replication was observed when the deletions that were made were located at the 3' rather than 5' end of the leader region. The potential of viral reversion over protracted periods was investigated by repeated viral passage in CEMx174 cells. The results showed that several of these constructs showed no signs of reversion after more than 6 months in tissue culture. Thus, a series of novel, attenuated SIV constructs have been developed that are significantly impaired in replication capacity yet retain all viral genes. One of these viruses, termed SD4, may be appropriate for study with rhesus macaques, in order to determine whether reversions will occur in vivo and to further study this virus as a candidate for attenuated vaccination.

* Corresponding author. Mailing address: McGill University AIDS Centre, Lady Davis Institute-Jewish General Hospital, 3755 Cote Ste-Catherine Rd., Montreal, Québec, Canada H3T 1E2. Phone: (514) 340-8260. Fax: (514) 340-7537. E-mail: mwainb1{at}po-box.mcgill.ca.

Journal of Virology, March 2001, p. 2776-2785, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2776-2785.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Quinto, I., Puca, A., Greenhouse, J., Silvera, P., Yalley-Ogunro, J., Lewis, M. G., Palmieri, C., Trimboli, F., Byrum, R., Adelsberger, J., Venzon, D., Chen, X., Scala, G. (2004). High Attenuation and Immunogenicity of a Simian Immunodeficiency Virus Expressing a Proteolysis-resistant Inhibitor of NF-{kappa}B. J. Biol. Chem. 279: 1720-1728 [Abstract] [Full Text]  
  • Strappe, P. M., Greatorex, J., Thomas, J., Biswas, P., McCann, E., Lever, A. M. L. (2003). The packaging signal of simian immunodeficiency virus is upstream of the major splice donor at a distance from the RNA cap site similar to that of human immunodeficiency virus types 1 and 2. J. Gen. Virol. 84: 2423-2430 [Abstract] [Full Text]  
  • Patel, J., Wang, S.-W., Izmailova, E., Aldovini, A. (2003). The Simian Immunodeficiency Virus 5' Untranslated Leader Sequence Plays a Role in Intracellular Viral Protein Accumulation and in RNA Packaging. J. Virol. 77: 6284-6292 [Abstract] [Full Text]  
  • Whitney, J. B., Oliveira, M., Detorio, M., Guan, Y., Wainberg, M. A. (2002). The M184V Mutation in Reverse Transcriptase Can Delay Reversion of Attenuated Variants of Simian Immunodeficiency Virus. J. Virol. 76: 8958-8962 [Abstract] [Full Text]  
  • von Gegerfelt, A. S., Liska, V., Li, P.-L., McClure, H. M., Horie, K., Nappi, F., Montefiori, D. C., Pavlakis, G. N., Marthas, M. L., Ruprecht, R. M., Felber, B. K. (2002). Rev-Independent Simian Immunodeficiency Virus Strains Are Nonpathogenic in Neonatal Macaques. J. Virol. 76: 96-104 [Abstract] [Full Text]  
  • Guan, Y., Diallo, K., Detorio, M., Whitney, J. B., Liang, C., Wainberg, M. A. (2001). Partial Restoration of Replication of Simian Immunodeficiency Virus by Point Mutations in either the Dimerization Initiation Site (DIS) or Gag Region after Deletion Mutagenesis within the DIS. J. Virol. 75: 11920-11923 [Abstract] [Full Text]  
  • Guan, Y., Diallo, K., Whitney, J. B., Liang, C., Wainberg, M. A. (2001). An Intact U5-Leader Stem Is Important for Efficient Replication of Simian Immunodeficiency Virus. J. Virol. 75: 11924-11929 [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»