14224
2011
eng
A228
Suppl. 1
8
article
1
2016-12-21
--
--
Regulation of foamy virus protease activity by viral RNA
No abstract available.
Retrovirology
10.1186/1742-4690-8-S1-A228
urn:nbn:de:bvb:20-opus-142248
Retrovirology 2011 8(Suppl 1):A228.
Maximilian J. Hartl
Jochen Bodem
Fabian Jochheim
Axel Rethwilm
Paul Rösch
Birgitta M. Wöhrl
eng
uncontrolled
Virologie
Krankheiten
open_access
Institut für Virologie und Immunbiologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14224/122_Hartl_Retrovirologie.pdf
6505
2012
eng
article
1
2013-03-26
--
--
The prototype foamy virus protease is active independently of the integrase domain
Background: Recently, contradictory results on foamy virus protease activity were published. While our own results indicated that protease activity is regulated by the viral RNA, others suggested that the integrase is involved in the regulation of the protease. Results: To solve this discrepancy we performed additional experiments showing that the protease-reverse transcriptase (PR-RT) exhibits protease activity in vitro and in vivo, which is independent of the integrase domain. In contrast, Pol incorporation, and therefore PR activity in the viral context, is dependent on the integrase domain. To further analyse the regulation of the protease, we incorporated Pol in viruses by expressing a GagPol fusion protein, which supported near wild-type like infectivity. A GagPR-RT fusion, lacking the integrase domain, also resulted in wild-type like Gag processing, indicating that the integrase is dispensable for viral Gag maturation. Furthermore, we demonstrate with a trans-complementation assays that the PR in the context of the PR-RT protein supports in trans both, viral maturation and infectivity. Conclusion: We provide evidence that the FV integrase is required for Pol encapsidation and that the FV PR activity is integrase independent. We show that an active PR can be encapsidated in trans as a GagPR-RT fusion protein.
urn:nbn:de:bvb:20-opus-75370
7537
In: Retrovirology (2012) 9: 41, doi:10.1186/1742-4690-9-41
Ralf Spannaus
Maximilian J. Hartl
Birgitta M. Wöhrl
Axel Rethwilm
Jochen Bodem
deu
swd
Medizin
eng
uncontrolled
Foamy virus
eng
uncontrolled
Regulation of protease activity
eng
uncontrolled
PARM
eng
uncontrolled
Integrase
eng
uncontrolled
GagPol fusion protein
Medizin und Gesundheit
open_access
Institut für Virologie und Immunbiologie
Förderzeitraum 2012
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6505/029_1742_4690_9_41.pdf
16642
2016
eng
2310–2322
5
44
article
1
2018-08-03
--
--
Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors
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.
Nucleic Acids Research
10.1093/nar/gkw060
urn:nbn:de:bvb:20-opus-166423
Nucleic Acids Research, 2016, Vol. 44, No. 5, 2310–2322. DOI: 10.1093/nar/gkw060
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Anna Schneider
Angela Corona
Imke Spöring
Mareike Jordan
Bernd Buchholz
Elias Maccioni
Roberto Di Santo
Jochen Bodem
Enzo Tramontano
Birgitta M. Wöhrl
eng
uncontrolled
ribonuclease H
eng
uncontrolled
HIV-1 subtype AG
eng
uncontrolled
azidothymidine
eng
uncontrolled
reverse transcriptase
eng
uncontrolled
multi-drug resistance
Biowissenschaften; Biologie
Medizin und Gesundheit
open_access
Institut für Virologie und Immunbiologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16642/Schneider_Nucleic_Acids_Research.pdf