Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Schneider, Anna [VerfasserIn]   i
 Buchholz, Bernd [VerfasserIn]   i
Titel:Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase
Titelzusatz:antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors
Verf.angabe:Anna Schneider, Angela Corona, Imke Spöring, Mareike Jordan, Bernd Buchholz, Elias Maccioni, Roberto Di Santo, Jochen Bodem, Enzo Tramontano and Birgitta M. Wöhrl
E-Jahr:2016
Jahr:4 February 2016
Umfang:13 S.
Fussnoten:Gesehen am 07.03.2019
Titel Quelle:Enthalten in: Nucleic acids research
Ort Quelle:Oxford : Oxford Univ. Press, 1974
Jahr Quelle:2016
Band/Heft Quelle:44(2016), 5, Seite 2310-2322
ISSN Quelle:1362-4962
Abstract:We analyzed a multi-drug resistant (MR) HIV-1 reverse transcriptase (RT), subcloned from a patient-derived subtype CRF02_AG, harboring 45 amino acid exchanges, amongst them four thymidine analog mutations (TAMs) relevant for high-level AZT (azidothymidine) resistance by AZTMP excision (M41L, D67N, T215Y, K219E) as well as four substitutions of the AZTTP discrimination pathway (A62V, V75I, F116Y and Q151M). In addition, K65R, known to antagonize AZTMP excision in HIV-1 subtype B was present. Although MR-RT harbored the most significant amino acid exchanges T215Y and Q151M of each pathway, it exclusively used AZTTP discrimination, indicating that the two mechanisms are mutually exclusive and that the Q151M pathway is obviously preferred since it confers resistance to most nucleoside inhibitors. A derivative was created, additionally harboring the TAM K70R and the reversions M151Q as well as R65K since K65R antagonizes excision. MR-R65K-K70R-M151Q was competent of AZTMP excision, whereas other combinations thereof with only one or two exchanges still promoted discrimination. To tackle the multi-drug resistance problem, we tested if the MR-RTs could still be inhibited by RNase H inhibitors. All MR-RTs exhibited similar sensitivity toward RNase H inhibitors belonging to different inhibitor classes, indicating the importance of developing RNase H inhibitors further as anti-HIV drugs.
DOI:doi:10.1093/nar/gkw060
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.1093/nar/gkw060
 Volltext: https://academic-oup-com.ezproxy.medma.uni-heidelberg.de/nar/article/44/5/2310/2465357
 DOI: https://doi.org/10.1093/nar/gkw060
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1588451828
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68367457   QR-Code
zum Seitenanfang