Ninety-nine is not enough: molecular characterization of inhibitor-resistant human immunodeficiency virus type 1 protease mutants with insertions in the flap region.

Journal of Virology
Milan KozísekJan Konvalinka

Abstract

While the selection of amino acid insertions in human immunodeficiency virus (HIV) reverse transcriptase (RT) is a known mechanism of resistance against RT inhibitors, very few reports on the selection of insertions in the protease (PR) coding region have been published. It is still unclear whether these insertions impact protease inhibitor (PI) resistance and/or viral replication capacity. We show that the prevalence of insertions, especially between amino acids 30 to 41 of HIV type 1 (HIV-1) PR, has increased in recent years. We identified amino acid insertions at positions 33 and 35 of the PR of HIV-1-infected patients who had undergone prolonged treatment with PIs, and we characterized the contribution of these insertions to viral resistance. We prepared the corresponding mutated, recombinant PR variants with or without insertions at positions 33 and 35 and characterized them in terms of enzyme kinetics and crystal structures. We also engineered the corresponding recombinant viruses and analyzed the PR susceptibility and replication capacity by recombinant virus assay. Both in vitro methods confirmed that the amino acid insertions at positions 33 and 35 contribute to the viral resistance to most of the tested PIs. The struc...Continue Reading

References

Jan 1, 1979·Methods in Enzymology·J W Williams, J F Morrison
Mar 1, 1990·Journal of Clinical Microbiology·R BoomJ van der Noordaa
Nov 23, 1990·Science·J P MooreQ J Sattentau
Jul 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·N E KohlI S Sigal
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Jones, J M Thornton
Oct 25, 2000·Protein Science : a Publication of the Protein Society·K StrisovskyH G Kräusslich
May 17, 2001·Antimicrobial Agents and Chemotherapy·B MasquelierUNKNOWN ANRS AC11 Resistance study group. French Agence Nationale de Recherches sur le SIDA
Dec 31, 2003·Methods in Enzymology·Martyn D WinnMiroslav Z Papiz
Jun 8, 2004·Current Drug Targets. Infectious Disorders·Jana PrejdováJan Konvalinka
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Oct 27, 2004·Acta Crystallographica. Section D, Biological Crystallography·Jirí BryndaJuraj Sedlácek
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jun 7, 2005·Protein Science : a Publication of the Protein Society·Ron M KaganKal Ramnarayan
Oct 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Petr CíglerJan Konvalinka
Apr 29, 2006·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Noortje M van MaarseveenMonique Nijhuis
Jul 21, 2006·Acta Crystallographica. Section D, Biological Crystallography·Wladek MinorMaksymilian Chruszcz
Jan 18, 2007·PLoS Medicine·Monique NijhuisCharles A B Boucher
Apr 5, 2007·PLoS Medicine·Nicholas A Buckley, David Gunnell
Apr 12, 2007·Expert Opinion on Pharmacotherapy·Carmen de MendozaVincent Soriano

❮ Previous
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Citations

Oct 12, 2010·Journal of Chemical Information and Modeling·Gene M KoRajni Garg
Jul 8, 2010·The Journal of Physical Chemistry. B·Ge-Fei HaoChang-Guo Zhan
Apr 29, 2009·AIDS Research and Human Retroviruses·Parris S JordanDavey M Smith
May 31, 2012·Antimicrobial Agents and Chemotherapy·Milan KozísekJochen Bodem
Apr 2, 2011·BMC Research Notes·Dominik HeiderDaniel Hoffmann
Oct 27, 2009·Antiviral Research·Annemarie M J WensingMonique Nijhuis
Jul 25, 2009·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·João Pereira-VazAntónio Meliço-Silvestre
Jul 21, 2009·Antiviral Research·Luis Menéndez-Arias
Jun 13, 2015·Future Medicinal Chemistry·Irene T WeberAndres Wong-Sam
Mar 31, 2015·Virology·Jan KonvalinkaBarbara Müller
Aug 14, 2012·Molecular Biology International·Catherine S Adamson
Dec 1, 2009·Viruses·Jana PokornáJan Konvalinka
Feb 23, 2019·Physical Chemistry Chemical Physics : PCCP·Pavel SrbVáclav Veverka
Sep 11, 2014·Biological Chemistry·Previn Naicker, Yasien Sayed
Jul 23, 2011·Revista Da Sociedade Brasileira De Medicina Tropical·Rejane Maria Tommasini GrottoMaria Inês de Moura Campos Pardini
Oct 31, 2014·Physical Chemistry Chemical Physics : PCCP·Eva KutálkováMarek Ingr
Mar 11, 2015·The Journal of Biological Chemistry·Jan TykvartJan Konvalinka

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