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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,
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.

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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