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PMID: 12634354 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The leader of human immunodeficiency virus type 1 genomic RNA harbors an internal ribosome entry segment that is active during the G2/M phase of the cell cycle.

Journal of virology ·Vol. 77 ·No. 7 ·2003-04-00 ·Pages 3939-49

Brasey A, Lopez-Lastra M, Ohlmann T, Beerens N, Berkhout B, Darlix JL, Sonenberg N

Abstract

The 5' leader of the human immunodeficiency virus type 1 (HIV-1) genomic RNA contains highly structured domains involved in key steps of the viral life cycle. These RNA domains inhibit cap-dependent protein synthesis. Here we report that the HIV-1 5' leader harbors an internal ribosome entry site (IRES) capable of driving protein synthesis during the G(2)/M cell cycle phase in which cap-dependent initiation is inhibited. The HIV-1 IRES was delineated with bicistronic mRNAs in in vitro and ex vivo assays. The HIV-1 leader IRES spans nucleotides 104 to 336 and partially overlaps the major determinants of genomic RNA packaging. These data strongly suggest that, as for HIV-1 transcription, IRES-mediated translation initiation could play an important role in virus replication during virus-induced G(2)/M cell cycle arrest.

MeSH Terms
5' Untranslated Regions/genetics Animals Base Sequence COS Cells Cell Line DNA, Viral/genetics Eukaryotic Initiation Factor-4G/metabolism G2 Phase Genes, Viral HIV-1/genetics,physiology HeLa Cells Humans Mitosis Mutation Protein Biosynthesis RNA, Viral/genetics Ribosomes/metabolism Virus Replication/genetics,physiology
Chemicals
5' Untranslated Regions DNA, Viral Eukaryotic Initiation Factor-4G RNA, Viral
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Brasey Ann
Biochemistry Department, McGill University, H3G 1Y6 Montréal, Canada.
Lopez-Lastra Marcelo
Ohlmann Theophile
Beerens Nancy
Berkhout Ben
Darlix Jean-Luc
Sonenberg Nahum
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.77.7.3939-3949.2003
Published
2003-04-00
Pages
3939-49
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC150645
Subset
IM
External Links
PubMed source DOI: 10.1128/jvi.77.7.3939-3949.2003 PMC Full Text View journal details
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