caa a22 4500 475845978 CHVBK 20180406123914.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/PL00000626 doi (NATIONALLICENCE)springer-10.1007/PL00000626 Molecular mechanisms of HIV-1 resistance to nucleoside reverse transcriptase inhibitors (NRTIs) [Elektronische Daten] [N. Sluis-Cremer, D. Arion, M. A. Parniak*] Abstract.: Nucleoside reverse transcriptase inhibitors (NRTIs), such as 3′-azido-3′-deoxythymidine, 2′,3′-dideoxyinosine and 2′,3′-dideoxy-3′-thiacytidine, are effective inhibitors of human immunodeficiency type 1 (HIV-1) replication. NRTIs are deoxynucleoside triphosphate analogs, but lack a free 3′-hydroxyl group. Once NRTIs are incorporated into the nascent viral DNA, in reactions catalyzed by HIV-1 reverse transcriptase (RT), further viral DNA synthesis is effectively terminated. NRTIs should therefore represent the ideal antiviral agent. Unfortunately, HIV-1 inevitably develops resistance to these inhibitors, and this resistance correlates with mutations in RT. To date, three phenotypic mechanisms have been identified or proposed to account for HIV-1 RT resistance to NRTIs. These mechanisms include alterations of RT discrimination between NRTIs and the analogous dNTP (direct effects on NRTI binding and/or incorporation), alterations in RT-template/primer interactions, which may influence subsequent NRTI incorporation, and enhanced removal of the chain-terminating residue from the 3′ end of the primer. These different resistance phenotypes seem to correlate with different sets of mutations in RT. This review discusses the relationship between HIV-1 drug resistance genotype and phenotype, in relation to our current knowledge of HIV-1 RT structure. Birkhäuser Verlag Basel,, 2000 Key words. Human immunodeficiency virus type 1 nationallicence reverse transcriptase nationallicence nucleoside reverse transcriptase inhibitors nationallicence DNA polymerization nationallicence chain termination nationallicence antiviral drug resistance nationallicence phosphorolysis nationallicence pyrophosphorolysis nationallicence Sluis-Cremer N. Lady Davis Institute for Medical Research and McGill University AIDS Centre, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montreal, Quebec H3T 1E2 (Canada), Fax +1514 340 7502, e-mail: mparniak@ldi.jgh.mcgill.ca, CA aut Arion D. Lady Davis Institute for Medical Research and McGill University AIDS Centre, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montreal, Quebec H3T 1E2 (Canada), Fax +1514 340 7502, e-mail: mparniak@ldi.jgh.mcgill.ca, CA aut Parniak* M. A. Lady Davis Institute for Medical Research and McGill University AIDS Centre, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montreal, Quebec H3T 1E2 (Canada), Fax +1514 340 7502, e-mail: mparniak@ldi.jgh.mcgill.ca, CA aut https://doi.org/10.1007/PL00000626 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00000626 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sluis-Cremer N. Lady Davis Institute for Medical Research and McGill University AIDS Centre, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montreal, Quebec H3T 1E2 (Canada), Fax +1514 340 7502, e-mail: mparniak@ldi.jgh.mcgill.ca, CA aut NATIONALLICENCE 700 1- Arion D. Lady Davis Institute for Medical Research and McGill University AIDS Centre, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montreal, Quebec H3T 1E2 (Canada), Fax +1514 340 7502, e-mail: mparniak@ldi.jgh.mcgill.ca, CA aut NATIONALLICENCE 700 1- Parniak* M. A. Lady Davis Institute for Medical Research and McGill University AIDS Centre, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montreal, Quebec H3T 1E2 (Canada), Fax +1514 340 7502, e-mail: mparniak@ldi.jgh.mcgill.ca, CA aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer