Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F12%3A00383709" target="_blank" >RIV/61388963:_____/12:00383709 - isvavai.cz</a>
Výsledek na webu
<a href="http://dx.doi.org/10.1128/AAC.00465-12" target="_blank" >http://dx.doi.org/10.1128/AAC.00465-12</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1128/AAC.00465-12" target="_blank" >10.1128/AAC.00465-12</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease
Popis výsledku v původním jazyce
During the last few decades, the treatment of HIV-infected patients by highly active antiretroviral therapy, including protease inhibitors (PIs), has become standard. Here, we present results of analysis of a patient-derived, multiresistant HIV-1 CRF02 AG recombinant strain with a highly mutated protease (PR) coding sequence, where up to 19 coding mutations have accumulated in the PR. The results of biochemical analysis in vitro showed that the patient-derived PR is highly resistant to most of the currently used PIs and that it also exhibits very poor catalytic activity. Determination of the crystal structure revealed prominent changes in the flap elbow region and S1/S1' active site subsites. While viral loads in the patient were found to be high, theinsertion of the patient-derived PR into a HIV-1 subtype B backbone resulted in reduction of infectivity by 3 orders of magnitude. Fitness compensation was not achieved by elevated polymerase (Pol) expression, but the introduction of pati
Název v anglickém jazyce
Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease
Popis výsledku anglicky
During the last few decades, the treatment of HIV-infected patients by highly active antiretroviral therapy, including protease inhibitors (PIs), has become standard. Here, we present results of analysis of a patient-derived, multiresistant HIV-1 CRF02 AG recombinant strain with a highly mutated protease (PR) coding sequence, where up to 19 coding mutations have accumulated in the PR. The results of biochemical analysis in vitro showed that the patient-derived PR is highly resistant to most of the currently used PIs and that it also exhibits very poor catalytic activity. Determination of the crystal structure revealed prominent changes in the flap elbow region and S1/S1' active site subsites. While viral loads in the patient were found to be high, theinsertion of the patient-derived PR into a HIV-1 subtype B backbone resulted in reduction of infectivity by 3 orders of magnitude. Fitness compensation was not achieved by elevated polymerase (Pol) expression, but the introduction of pati
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
EE - Mikrobiologie, virologie
OECD FORD obor
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Návaznosti výsledku
Projekt
<a href="/cs/project/GAP207%2F11%2F1798" target="_blank" >GAP207/11/1798: Inhibitory proteasy z viru HIV: mechanismus účinku a vývoj resistence</a><br>
Návaznosti
Z - Vyzkumny zamer (s odkazem do CEZ)
Ostatní
Rok uplatnění
2012
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Antimicrobial Agents and Chemotherapy
ISSN
0066-4804
e-ISSN
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Svazek periodika
56
Číslo periodika v rámci svazku
8
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
11
Strana od-do
4320-4330
Kód UT WoS článku
000306826300036
EID výsledku v databázi Scopus
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