Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Mutations in HIV-1 gag and pol Compensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease
Original language 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, 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
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EE - Microbiology, virology
OECD FORD branch
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Result continuities
Project
<a href="/en/project/GAP207%2F11%2F1798" target="_blank" >GAP207/11/1798: HIV protease inhibitors: mechanism of action and resistance development</a><br>
Continuities
Z - Vyzkumny zamer (s odkazem do CEZ)
Others
Publication year
2012
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Antimicrobial Agents and Chemotherapy
ISSN
0066-4804
e-ISSN
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Volume of the periodical
56
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
4320-4330
UT code for WoS article
000306826300036
EID of the result in the Scopus database
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