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J Virol, July 1998, p. 6146-6150, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Novel Gag-Pol Frameshift Site in Human Immunodeficiency Virus Type 1 Variants Resistant to Protease Inhibitors

Louise Doyon,1 Catherine Payant,2 Léa Brakier-Gingras,2 and Daniel Lamarre1,*

Bio-Méga Research Division, Boehringer Ingelheim (Canada) Ltd., Laval, Quebec, Canada H7S 2G5,1 and Département de Biochimie, Université de Montréal, Montréal, Quebec, Canada H3C 3J72

Received 29 September 1997/Accepted 25 March 1998

Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease inhibitors have been shown to contain a mutation in the p1/p6 Gag precursor cleavage site. At the messenger RNA level, this mutation generates a U UUU UUU sequence that is reminiscent of the U UUU UUA sequence required for ribosomal frameshifting and Gag-Pol synthesis. To test whether the p1/p6 cleavage site mutation was generating a novel frameshift site, HIV sequences were inserted in translation vectors containing a chloramphenicol acetyltransferase (CAT) reporter gene requiring -1 frameshifting for expression. All sequences containing the original HIV frameshift site supported the synthesis of CAT but expression was increased 3- to 11-fold in the presence of the mutant p1/p6 sequence. When the original frameshift site was abolished by mutation, expression remained unchanged when using constructs containing the mutant p1/p6 sequence, whereas it was decreased 2- to 4.5-fold when using wild-type p1/p6 constructs. Similarly, when introduced into HIV molecular clones, the p1/p6 mutant sequence supported Gag-Pol synthesis and protease activity in the absence of the original frameshift site, indicating that this sequence could also promote ribosomal frameshifting in virus-expressing cells.

* Corresponding author. Mailing address: Bio-Méga Research Division, Boehringer Ingelheim (Canada) Ltd., 2100 Cunard, Laval, Quebec, Canada H7S 2G5. Phone: (514) 682-4640. Fax: (514) 682-8434. E-mail: dlamarre{at}bio-mega.boehringer-ingelheim.ca.

J Virol, July 1998, p. 6146-6150, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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