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Journal of Virology, September 1998, p. 7676-7680, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mutations in the Primer Grip of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Impair Proviral DNA Synthesis and Virion Maturation

Qiang Yu,1 Michele Ottmann,1,dagger Christine Pechoux,1 Stuart Le Grice,2 and Jean-Luc Darlix1,*

LaboRetro, Unité de Virologie Humaine INSERM U412, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France,1 and Center for AIDS Research and Division of Infectious Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio 441062

Received 18 March 1998/Accepted 27 May 1998

This report describes the effects of mutating highly conserved residues in the primer grip domain of human immunodeficiency virus type 1 reverse transcriptase (RT) on virus formation and infectivity. Among a series of RT mutant viruses, three (M230A, L234D, and W239A) were found to be noninfectious or very poorly infectious. Our data indicate that these mutations in RT caused severe defects in proviral DNA synthesis. Interestingly, assembly and maturation of mutant virus M230A were similar to those of the wild type, while mutants L234D and W239A showed impaired maturation. The immature morphology of RT mutants L234D and W239A is due at least in part to premature cleavage of the gag-pol precursor, prior to virion budding, indicating that intracellular stability of Pr160gag-pol is of key importance during virus assembly.

* Corresponding author. Mailing address: LaboRetro, Unité de Virologie Humaine INSERM U412, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France. Phone: 334-72-72-81-69. Fax: 334-72-72-86-86. E-mail: Jean-Luc.Darlix{at}ens-lyon.fr.

dagger Present address: Lab. déficits immunitaires, Faculté de Medecine RTH Laennec, 69372 Lyon Cedex 08, France.

Journal of Virology, September 1998, p. 7676-7680, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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