This HTML5 document contains 56 embedded RDF statements represented using HTML+Microdata notation.

The embedded RDF content will be recognized by any processor of HTML5 Microdata.

Namespace Prefixes

PrefixIRI
dctermshttp://purl.org/dc/terms/
n13http://linked.opendata.cz/resource/domain/vavai/riv/tvurce/
n8http://linked.opendata.cz/resource/domain/vavai/projekt/
n18http://linked.opendata.cz/resource/domain/vavai/subjekt/
n16http://linked.opendata.cz/ontology/domain/vavai/
n19http://linked.opendata.cz/resource/domain/vavai/vysledek/RIV%2F61388963%3A_____%2F12%3A00383709%21RIV13-AV0-61388963/
n17http://linked.opendata.cz/resource/domain/vavai/zamer/
shttp://schema.org/
skoshttp://www.w3.org/2004/02/skos/core#
n3http://linked.opendata.cz/ontology/domain/vavai/riv/
n9http://bibframe.org/vocab/
n2http://linked.opendata.cz/resource/domain/vavai/vysledek/
rdfhttp://www.w3.org/1999/02/22-rdf-syntax-ns#
n11http://linked.opendata.cz/ontology/domain/vavai/riv/klicoveSlovo/
n14http://linked.opendata.cz/ontology/domain/vavai/riv/duvernostUdaju/
xsdhhttp://www.w3.org/2001/XMLSchema#
n12http://linked.opendata.cz/ontology/domain/vavai/riv/aktivita/
n6http://linked.opendata.cz/ontology/domain/vavai/riv/jazykVysledku/
n5http://linked.opendata.cz/ontology/domain/vavai/riv/obor/
n4http://linked.opendata.cz/ontology/domain/vavai/riv/druhVysledku/
n20http://reference.data.gov.uk/id/gregorian-year/

Statements

Subject Item
n2:RIV%2F61388963%3A_____%2F12%3A00383709%21RIV13-AV0-61388963
rdf:type
skos:Concept n16:Vysledek
dcterms:description
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, the insertion 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 patient-derived gag and pol sequences in a CRF02 AG backbone rescued viral infectivity to near wild-type (wt) levels. The mutations that accumulated in the vicinity of the processing sites spanning the p2/NC, NC/p1, and p6pol/PR proteins lead to much more efficient hydrolysis of corresponding peptides by patient-derived PR in comparison to the wt enzyme. This indicates a very efficient coevolution of enzyme and substrate maintaining high viral loads in vivo under constant drug pressure. 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, the insertion 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 patient-derived gag and pol sequences in a CRF02 AG backbone rescued viral infectivity to near wild-type (wt) levels. The mutations that accumulated in the vicinity of the processing sites spanning the p2/NC, NC/p1, and p6pol/PR proteins lead to much more efficient hydrolysis of corresponding peptides by patient-derived PR in comparison to the wt enzyme. This indicates a very efficient coevolution of enzyme and substrate maintaining high viral loads in vivo under constant drug pressure.
dcterms:title
Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease
skos:prefLabel
Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease
skos:notation
RIV/61388963:_____/12:00383709!RIV13-AV0-61388963
n16:predkladatel
n18:ico%3A61388963
n3:aktivita
n12:P n12:Z
n3:aktivity
P(GAP207/11/1798), Z(AV0Z40550506)
n3:cisloPeriodika
8
n3:dodaniDat
n20:2013
n3:domaciTvurceVysledku
n13:6745725 n13:7120532 n13:6934447 n13:7029853
n3:druhVysledku
n4:J
n3:duvernostUdaju
n14:S
n3:entitaPredkladatele
n19:predkladatel
n3:idSjednocenehoVysledku
152549
n3:idVysledku
RIV/61388963:_____/12:00383709
n3:jazykVysledku
n6:eng
n3:klicovaSlova
HIV protease; resistance; inhibitor; viral fitness; AG subtype
n3:klicoveSlovo
n11:viral%20fitness n11:inhibitor n11:AG%20subtype n11:resistance n11:HIV%20protease
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[F3DCAF8AFD3D]
n3:nazevZdroje
Antimicrobial Agents and Chemotherapy
n3:obor
n5:EE
n3:pocetDomacichTvurcuVysledku
4
n3:pocetTvurcuVysledku
11
n3:projekt
n8:GAP207%2F11%2F1798
n3:rokUplatneniVysledku
n20:2012
n3:svazekPeriodika
56
n3:tvurceVysledku
Buchholz, B. Müller, V. Grantz Šašková, Klára Konvalinka, Jan Řezáčová, Pavlína Kožíšek, Milan Jacobs, G. B. Kräusslich, H. G. Bodem, J. Henke, S. Schuch, A.
n3:wos
000306826300036
n3:zamer
n17:AV0Z40550506
s:issn
0066-4804
s:numberOfPages
11
n9:doi
10.1128/AAC.00465-12