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J. Virol. doi:10.1128/JVI.01028-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Both linear and discontinuous ribosome scanning are used for translation initiation from bicistronic HIV-1 env mRNAs

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

^* To whom correspondence should be addressed. Email: dfjp{at}unimelb.edu.au.

	Abstract

Human immunodeficiency virus type 1 (HIV-1) generates 16 alternatively spliced isoforms of env mRNA that contain the same overlapping open reading frames (ORFs) for Vpu and Env protein but differ in their 5' untranslated regions (UTR). A subset of env mRNA encode the extra upstream Rev initiation codon in the 5' UTR. We explored the effect of the alternative UTR on translation of Vpu and Env proteins from authentic env mRNA expressed from cDNA constructs. Vpu expression was minimal from the subset of env mRNA isoforms with exons containing an upstream Rev AUG codon. However, every env mRNA isoform expressed a similar level of Env protein. Mutations that removed, altered the strength, or introduced upstream AUGs dramatically altered Vpu expression, but had little impact on the consistent expression of Env. These data show 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.

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