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Journal of Virology, May 2007, p. 4664-4676, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.01028-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Both Linear and Discontinuous Ribosome Scanning Are Used for Translation Initiation from Bicistronic Human Immunodeficiency Virus Type 1 env mRNAs{triangledown} ,{dagger}

Jenny L. Anderson,{ddagger} Adam T. Johnson, Jane L. Howard, and Damian F. J. Purcell*

Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC 3010, Australia

Received 18 May 2006/ Accepted 17 February 2007

Human immunodeficiency virus type 1 (HIV-1) generates 16 alternatively spliced isoforms of env mRNA that contain the same overlapping open reading frames for Vpu and Env proteins but differ in their 5' untranslated regions (UTR). A subset of env mRNAs carry the extra upstream Rev initiation codon in the 5' UTR. We explored the effect of the alternative UTR on the translation of Vpu and Env proteins from authentic env mRNAs expressed from cDNA constructs. Vpu expression from the subset of env mRNA isoforms with exons containing an upstream Rev AUG codon was minimal. However, every env mRNA isoform expressed similar levels of Env protein. Mutations that removed, altered the strength of, or introduced upstream AUG codons dramatically altered Vpu expression but had little impact on the consistent expression of Env. These data show that the different isoforms of env mRNA are not redundant but instead regulate Vpu production in HIV-1-infected cells. Furthermore, while the initiation of Vpu translation conforms to the leaky ribosome-scanning model, the consistent Env synthesis infers a novel, discontinuous ribosome-scanning mechanism to translate Env.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, The University of Melbourne, Parkville 3010, Victoria, Australia. Phone: 61-3-8344-6753. Fax: 61-3-9347-1540. E-mail: dfjp{at}unimelb.edu.au

{triangledown} Published ahead of print on 28 February 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.

Journal of Virology, May 2007, p. 4664-4676, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.01028-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Asang, C., Hauber, I., Schaal, H. (2008). Insights into the selective activation of alternatively used splice acceptors by the human immunodeficiency virus type-1 bidirectional splicing enhancer. Nucleic Acids Res 36: 1450-1463 [Abstract] [Full Text]  


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