PMID: 9525657Apr 3, 1998Paper

Loss of viral fitness associated with multiple Gag and Gag-Pol processing defects in human immunodeficiency virus type 1 variants selected for resistance to protease inhibitors in vivo

Journal of Virology
V ZennouF Clavel

Abstract

We examined the viral replicative capacity and protease-mediated processing of Gag and Gag-Pol precursors of human immunodeficiency virus (HIV) variants selected for resistance to protease inhibitors. We compared recombinant viruses carrying plasma HIV RNA protease sequences obtained from five patients before protease inhibitor therapy and after virus escape from the treatment. Paired pretherapy-postresistance reconstructed viruses were evaluated for HIV infectivity in a quantitative single-cycle titration assay and in a lymphoid cell propagation assay. We found that all reconstructed resistant viruses had a reproducible decrease in their replicative capacity relative to their parental pretherapy counterparts. The extent of this loss of infectivity was pronounced for some viruses and more limited for others, irrespective of the inhibitor used and of the level of resistance. In resistant viruses, the efficiency of Gag and Gag-Pol precursor cleavage by the protease was impaired to different extents, as shown by the accumulation of several cleavage intermediates in purified particle preparations. We conclude that protease inhibitor-resistant HIV variants selected during therapy have an impaired replicative capacity related to mult...Continue Reading

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Citations

Dec 22, 1999·The New England Journal of Medicine·N Clumeck
Sep 27, 2000·Proceedings of the National Academy of Sciences of the United States of America·J Martinez-PicadoR T D'Aquila
Jul 13, 2000·Reviews in Medical Virology·D PillayD D Richman
Sep 5, 2001·Journal of Virology·B BühlerB E Torbett
Aug 16, 2002·European Journal of Biochemistry·Anita FehérJózsef Tözsér
Sep 28, 2002·Proceedings. Biological Sciences·Sebastian BonhoefferRob J De Boer
Sep 10, 2003·Journal of Leukocyte Biology·Maureen M GoodenowJohn W Sleasman
Jun 9, 2006·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Wendy P BannisterUNKNOWN EuroSIDA Study Group
Jun 6, 2007·Current HIV/AIDS Reports·David R BangsbergSteven G Deeks
Feb 2, 2011·Antimicrobial Agents and Chemotherapy·Lucile LarrouyDiane Descamps
Dec 15, 2010·Antimicrobial Agents and Chemotherapy·Chris M ParryDeenan Pillay
Dec 15, 2010·AIDS Research and Human Retroviruses·Fernando Flor-ParraPilar Pérez-Romero
Jul 1, 2010·Viruses·François Clavel, Fabrizio Mammano
Nov 30, 2000·Current Infectious Disease Reports·G J Hanna, R T D'Aquila
Feb 15, 2001·The New England Journal of Medicine·L M Frenkel, J I Mullins
Mar 27, 2001·Journal of Acquired Immune Deficiency Syndromes : JAIDS·V Miller
Aug 15, 2002·Paediatric Drugs·Patrick J Gavin, Ram Yogev
Jan 31, 2002·AIDS·B Larder
Nov 8, 2001·AIDS·A M van RossumUNKNOWN Dutch Study Group for Children with HIV Infections
May 21, 2005·AIDS·Eric S DaarUNKNOWN Hemophilia Growth and Development Study

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