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Journal of Virology, March 2003, p. 3345-3350, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3345-3350.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Replacement of Murine Leukemia Virus Readthrough Mechanism by Human Immunodeficiency Virus Frameshift Allows Synthesis of Viral Proteins and Virus Replication

Marie-Noëlle Brunelle,1 Léa Brakier-Gingras,1 and Guy Lemay2*

Département de Biochimie,1 Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada H3C 3J72

Received 19 September 2002/ Accepted 3 December 2002

Retroviruses use unusual recoding strategies to synthesize the Gag-Pol polyprotein precursor of viral enzymes. In human immunodeficiency virus, ribosomes translating full-length viral RNA can shift back by 1 nucleotide at a specific site defined by the presence of both a slippery sequence and a downstream stimulatory element made of an extensive secondary structure. This so-called frameshift mechanism could become a target for the development of novel antiviral strategies. A different recoding strategy is used by other retroviruses, such as murine leukemia viruses, to synthesize the Gag-Pol precursor; in this case, a stop codon is suppressed in a readthrough process, again due to the presence of a specific structure adopted by the mRNA. Development of antiframeshift agents will greatly benefit from the availability of a simple animal and virus model. For this purpose, the murine leukemia virus readthrough region was rendered inactive by mutagenesis and the frameshift region of human immunodeficiency virus was inserted to generate a chimeric provirus. This substitution of readthrough by frameshift allows the synthesis of viral proteins, and the chimeric provirus sequence was found to generate infectious viruses. This system could be a most interesting alternative to study ribosomal frameshift in the context of a virus amenable to the use of a simple animal model.


* Corresponding author. Mailing address: Département de Microbiologie et Immunologie, Université de Montréal, P.O. Box 6128, Station Centre-Ville, Montréal, Québec, Canada H3C 3J7. Phone: (514) 343-2422. Fax: (514) 343-5701. E-mail: guy.lemay{at}umontreal.ca.


Journal of Virology, March 2003, p. 3345-3350, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3345-3350.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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