This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Biswas, P. Articles by Peltz, S. W. Search for Related Content PubMed PubMed Citation Articles by Biswas, P. Articles by Peltz, S. W.

The Human Immunodeficiency Virus Type 1 Ribosomal Frameshifting Site Is an Invariant Sequence Determinant and an Important Target for Antiviral Therapy

Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854,¹ PTC Therapeutics, South Plainfield, New Jersey 07080²

Received 14 April 2003/ Accepted 24 October 2003

Human immunodeficiency virus type 1 (HIV-1) utilizes a distinctive form of gene regulation as part of its life cycle, termed programmed -1 ribosomal frameshifting, to produce the required ratio of the Gag and Gag-Pol polyproteins. We carried out a sequence comparison of 1,000 HIV-1 sequences at the slippery site (UUUUUUA) and found that the site is invariant, which is somewhat surprising for a virus known for its variability. This prompted us to prepare a series of mutations to examine their effect upon frameshifting and viral infectivity. Among the series of mutations were changes of the HIV-1 slippery site to those effectively utilized by other viruses, because such mutations would be anticipated to have a relatively mild effect upon frameshifting. The results demonstrate that any change to the slippery site reduced frameshifting levels and also dramatically inhibited infectivity. Because ribosomal frameshifting is essential for HIV-1 replication and it is surprisingly resistant to mutation, modulation of HIV-1 frameshifting efficiency potentially represents an important target for the development of novel antiviral therapeutics.

This article has been cited by other articles:

• Dulude, D., Theberge-Julien, G., Brakier-Gingras, L., Heveker, N. (2008). Selection of peptides interfering with a ribosomal frameshift in the human immunodeficiency virus type 1. RNA 14: 981-991 [Abstract] [Full Text]  
• Gendron, K., Charbonneau, J., Dulude, D., Heveker, N., Ferbeyre, G., Brakier-Gingras, L. (2008). The presence of the TAR RNA structure alters the programmed -1 ribosomal frameshift efficiency of the human immunodeficiency virus type 1 (HIV-1) by modifying the rate of translation initiation. Nucleic Acids Res 36: 30-40 [Abstract] [Full Text]  
• Leger, M., Dulude, D., Steinberg, S. V., Brakier-Gingras, L. (2007). The three transfer RNAs occupying the A, P and E sites on the ribosome are involved in viral programmed -1 ribosomal frameshift. Nucleic Acids Res 0: gkm578v1-12 [Abstract] [Full Text]  
• Zook, M. B., Howard, M. T., Sinnathamby, G., Atkins, J. F., Eisenlohr, L. C. (2006). Epitopes Derived by Incidental Translational Frameshifting Give Rise to a Protective CTL Response.. J. Immunol. 176: 6928-6934 [Abstract] [Full Text]  
• Muldoon-Jacobs, K. L., Dinman, J. D. (2006). Specific effects of ribosome-tethered molecular chaperones on programmed -1 ribosomal frameshifting.. Eukaryot Cell 5: 762-770 [Abstract] [Full Text]  
• Cornish, P. V., Hennig, M., Giedroc, D. P. (2005). A loop 2 cytidine-stem 1 minor groove interaction as a positive determinant for pseudoknot-stimulated -1 ribosomal frameshifting. Proc. Natl. Acad. Sci. USA 102: 12694-12699 [Abstract] [Full Text]