Human Immunodeficiency Virus Type 1 Protease and the Emergence of Drug Resistance
Publikation: Bog/antologi/afhandling/rapport › Ph.d.-afhandling › Forskning
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Human Immunodeficiency Virus Type 1 Protease and the Emergence of Drug Resistance. / Poulsen, Nina Rødtness.
Department of Biology, Faculty of Science, University of Copenhagen, 2016.Publikation: Bog/antologi/afhandling/rapport › Ph.d.-afhandling › Forskning
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TY - BOOK
T1 - Human Immunodeficiency Virus Type 1 Protease and the Emergence of Drug Resistance
AU - Poulsen, Nina Rødtness
PY - 2016
Y1 - 2016
N2 - Human immunodeficiency virus type-1 (HIV-1) protease (PR) is responsible for cleaving ten different sites in the viral Gag and Gag-pol polyproteins, thereby releasing the structural proteins and enzymes necessary for the maturation and infectivity of the HIV-1 virus. The vital role of HIV-1 PR in the virus life cycle has made it a major target for drug development and active site competitive inhibitors have been successful in the battle against HIV. Unfortunately, the massive drug pressure along with high-level replication and lack of proofreading by the viral reverse transcriptase have resulted in multi-drug-resistant PRs. Computational analysis of a vast number of inhibitor-resistant HIV-1 PR variants can broaden the knowledge of how and why the mutations arise, which would be a great advantage in the design on resistance-evading inhibitors. Here we present a diverse system to select for catalytically active HIV-1 PR in the presence of inhibitor. The system is based on the protein AraC, which regulates transcription of the araA, araB and araD genes necessary for arabinose catabolism in Escherichia coli, and its effectiveness was demonstrated by the isolation of both known and unknown inhibitor-resistant HIV-1 PR variants.
AB - Human immunodeficiency virus type-1 (HIV-1) protease (PR) is responsible for cleaving ten different sites in the viral Gag and Gag-pol polyproteins, thereby releasing the structural proteins and enzymes necessary for the maturation and infectivity of the HIV-1 virus. The vital role of HIV-1 PR in the virus life cycle has made it a major target for drug development and active site competitive inhibitors have been successful in the battle against HIV. Unfortunately, the massive drug pressure along with high-level replication and lack of proofreading by the viral reverse transcriptase have resulted in multi-drug-resistant PRs. Computational analysis of a vast number of inhibitor-resistant HIV-1 PR variants can broaden the knowledge of how and why the mutations arise, which would be a great advantage in the design on resistance-evading inhibitors. Here we present a diverse system to select for catalytically active HIV-1 PR in the presence of inhibitor. The system is based on the protein AraC, which regulates transcription of the araA, araB and araD genes necessary for arabinose catabolism in Escherichia coli, and its effectiveness was demonstrated by the isolation of both known and unknown inhibitor-resistant HIV-1 PR variants.
UR - https://soeg.kb.dk/permalink/45KBDK_KGL/fbp0ps/alma99122244509505763
M3 - Ph.D. thesis
BT - Human Immunodeficiency Virus Type 1 Protease and the Emergence of Drug Resistance
PB - Department of Biology, Faculty of Science, University of Copenhagen
ER -
ID: 168876463