| Attributes | Values |
|---|
| rdf:type
| |
| Description
| - Mutations in the substrate of the HIV-1 protease, especially changes in the NC/p1 cleavage site, can act not only as compensatory mutations but can also directly contribute to protease inhibitor (PI) resistance. These NC/p1 changes bring about PI resistance by causing an enhanced processing of the Gag protein. To investigate the capacity of HIV to modulate Gag cleavage and its consequences for protease inhibitor resistance and replicative capacity (RC), we performed a detailed enzymatic and virological analysis using a set of PI resistant NC/p1 variants (HXB2436E+437T, HXB2437T, HXB2437V and HXB2431V). Here we demonstrate that single NC/p1 mutants, which displayed only a slight increase in PI resistance didn’t show an obvious change in RC. In contrast, the double NC/p1 mutant, which displayed a clear increase in processing efficiency and PI resistance, also demonstrated a clear reduction in RC. Evolution experiments revealed that this decrease in RC could be (partially) restored by either reversion of the 436E change or by the acquisition of additional changes at codon 435 or 438. Furthermore, these changes also normalized Gag processing efficiency and returned PI susceptibility in the direction of wild type level. The results of this study demonstrate that when enhanced Gag processing due to PI resistance mutations in NC/p1 reduces RC, HIV-1 can modulate the NC/p1 sequence to restore RC and Gag cleavage to an optimal rate.
- Mutations in the substrate of the HIV-1 protease, especially changes in the NC/p1 cleavage site, can act not only as compensatory mutations but can also directly contribute to protease inhibitor (PI) resistance. These NC/p1 changes bring about PI resistance by causing an enhanced processing of the Gag protein. To investigate the capacity of HIV to modulate Gag cleavage and its consequences for protease inhibitor resistance and replicative capacity (RC), we performed a detailed enzymatic and virological analysis using a set of PI resistant NC/p1 variants (HXB2436E+437T, HXB2437T, HXB2437V and HXB2431V). Here we demonstrate that single NC/p1 mutants, which displayed only a slight increase in PI resistance didn’t show an obvious change in RC. In contrast, the double NC/p1 mutant, which displayed a clear increase in processing efficiency and PI resistance, also demonstrated a clear reduction in RC. Evolution experiments revealed that this decrease in RC could be (partially) restored by either reversion of the 436E change or by the acquisition of additional changes at codon 435 or 438. Furthermore, these changes also normalized Gag processing efficiency and returned PI susceptibility in the direction of wild type level. The results of this study demonstrate that when enhanced Gag processing due to PI resistance mutations in NC/p1 reduces RC, HIV-1 can modulate the NC/p1 sequence to restore RC and Gag cleavage to an optimal rate. (en)
|
| Title
| - Modulation of HIV-1 Gag NC/p1 cleavage efficiency affects protease inhibitor resistance and viral replicative capacity
- Modulation of HIV-1 Gag NC/p1 cleavage efficiency affects protease inhibitor resistance and viral replicative capacity (en)
|
| skos:prefLabel
| - Modulation of HIV-1 Gag NC/p1 cleavage efficiency affects protease inhibitor resistance and viral replicative capacity
- Modulation of HIV-1 Gag NC/p1 cleavage efficiency affects protease inhibitor resistance and viral replicative capacity (en)
|
| skos:notation
| - RIV/61388963:_____/12:00377476!RIV13-AV0-61388963
|
| http://linked.open...avai/predkladatel
| |
| http://linked.open...avai/riv/aktivita
| |
| http://linked.open...avai/riv/aktivity
| |
| http://linked.open...iv/cisloPeriodika
| |
| http://linked.open...vai/riv/dodaniDat
| |
| http://linked.open...aciTvurceVysledku
| |
| http://linked.open.../riv/druhVysledku
| |
| http://linked.open...iv/duvernostUdaju
| |
| http://linked.open...titaPredkladatele
| |
| http://linked.open...dnocenehoVysledku
| |
| http://linked.open...ai/riv/idVysledku
| - RIV/61388963:_____/12:00377476
|
| http://linked.open...riv/jazykVysledku
| |
| http://linked.open.../riv/klicovaSlova
| - HIV-1; protease; Gag; resistance; cleavage (en)
|
| http://linked.open.../riv/klicoveSlovo
| |
| http://linked.open...odStatuVydavatele
| - GB - Spojené království Velké Británie a Severního Irska
|
| http://linked.open...ontrolniKodProRIV
| |
| http://linked.open...i/riv/nazevZdroje
| |
| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
| |
| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...UplatneniVysledku
| |
| http://linked.open...v/svazekPeriodika
| |
| http://linked.open...iv/tvurceVysledku
| - Lepšík, Martin
- Fun, A.
- Maarseveen van, N. M.
- Nijhuis, M.
- Schipper, P. J.
- Andersson, Dan
- Boucher, Ch. A. B.
- Jong de, D.
|
| http://linked.open...ain/vavai/riv/wos
| |
| http://linked.open...n/vavai/riv/zamer
| |
| issn
| |
| number of pages
| |
| http://bibframe.org/vocab/doi
| |
| is http://linked.open...avai/riv/vysledek
of | |
![[RDF Data]](/fct/images/sw-rdf-blue.png)
![[cxml]](/fct/images/cxml_doc.png)
![[csv]](/fct/images/csv_doc.png)
![[text]](/fct/images/ntriples_doc.png)
![[turtle]](/fct/images/n3turtle_doc.png)
![[ld+json]](/fct/images/jsonld_doc.png)
![[rdf+json]](/fct/images/json_doc.png)
![[rdf+xml]](/fct/images/xml_doc.png)
![[atom+xml]](/fct/images/atom_doc.png)
![[html]](/fct/images/html_doc.png)