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Journal of Virology, April 2003, p. 3939-3949, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.3939-3949.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Ann Brasey,1 Marcelo Lopez-Lastra,1 Theophile Ohlmann,2 Nancy Beerens,3 Ben Berkhout,3 Jean-Luc Darlix,2 and Nahum Sonenberg1*

Biochemistry Department, McGill University, H3G 1Y6 Montréal, Canada,1 LaboRetro, INSERM U 412, École Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France,2 Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, The Netherlands3

Received 10 September 2002/ Accepted 10 January 2003

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 G2/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 G2/M cell cycle arrest.

* Corresponding author. Mailing address: Biochemistry Department, Room 807, McIntyre Medical Sciences Building, McGill University, 3655 Promenade Sir William Osler, H3G 1Y6 Montréal, Canada. Phone: (514) 398-7274. Fax: (514) 398-1287. E-mail: nahum.sonenberg{at}mcgill.ca.

Journal of Virology, April 2003, p. 3939-3949, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.3939-3949.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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