Role of Gag in HIV Resistance to Protease Inhibitors
Cleavage of Gag and Gag-Pol precursors by the viral protease is an essential step in the replication cycle of HIV. Protease inhibitors, which compete with natural cleavage sites, strongly impair viral infectivity and have proven to be highly valuable in the treatment of HIV-infected subjects. Howeve...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Molecular Diversity Preservation International (MDPI)
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185719/ https://www.ncbi.nlm.nih.gov/pubmed/21994687 http://dx.doi.org/10.3390/v2071411 |
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author | Clavel, François Mammano, Fabrizio |
author_facet | Clavel, François Mammano, Fabrizio |
author_sort | Clavel, François |
collection | PubMed |
description | Cleavage of Gag and Gag-Pol precursors by the viral protease is an essential step in the replication cycle of HIV. Protease inhibitors, which compete with natural cleavage sites, strongly impair viral infectivity and have proven to be highly valuable in the treatment of HIV-infected subjects. However, as with all other antiretroviral drugs, the clinical benefit of protease inhibitors can be compromised by resistance. One key feature of HIV resistance to protease inhibitors is that the mutations that promote resistance are not only located in the protease itself, but also in some of its natural substrates. The best documented resistance-associated substrate mutations are located in, or near, the cleavage sites in the NC/SP2/p6 region of Gag. These mutations improve interactions between the substrate and the mutated enzyme and correspondingly increase cleavage. Initially described as compensatory mutations able to partially correct the loss of viral fitness that results from protease mutations, changes in Gag are now recognized as being directly involved in resistance. Besides NC/SP2/p6 mutations, polymorphisms in other regions of Gag have been found to exert various effects on viral fitness and or resistance, but their importance deserves further evaluation. |
format | Online Article Text |
id | pubmed-3185719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-31857192011-10-12 Role of Gag in HIV Resistance to Protease Inhibitors Clavel, François Mammano, Fabrizio Viruses Review Cleavage of Gag and Gag-Pol precursors by the viral protease is an essential step in the replication cycle of HIV. Protease inhibitors, which compete with natural cleavage sites, strongly impair viral infectivity and have proven to be highly valuable in the treatment of HIV-infected subjects. However, as with all other antiretroviral drugs, the clinical benefit of protease inhibitors can be compromised by resistance. One key feature of HIV resistance to protease inhibitors is that the mutations that promote resistance are not only located in the protease itself, but also in some of its natural substrates. The best documented resistance-associated substrate mutations are located in, or near, the cleavage sites in the NC/SP2/p6 region of Gag. These mutations improve interactions between the substrate and the mutated enzyme and correspondingly increase cleavage. Initially described as compensatory mutations able to partially correct the loss of viral fitness that results from protease mutations, changes in Gag are now recognized as being directly involved in resistance. Besides NC/SP2/p6 mutations, polymorphisms in other regions of Gag have been found to exert various effects on viral fitness and or resistance, but their importance deserves further evaluation. Molecular Diversity Preservation International (MDPI) 2010-07-05 /pmc/articles/PMC3185719/ /pubmed/21994687 http://dx.doi.org/10.3390/v2071411 Text en © 2010 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Review Clavel, François Mammano, Fabrizio Role of Gag in HIV Resistance to Protease Inhibitors |
title | Role of Gag in HIV Resistance to Protease Inhibitors |
title_full | Role of Gag in HIV Resistance to Protease Inhibitors |
title_fullStr | Role of Gag in HIV Resistance to Protease Inhibitors |
title_full_unstemmed | Role of Gag in HIV Resistance to Protease Inhibitors |
title_short | Role of Gag in HIV Resistance to Protease Inhibitors |
title_sort | role of gag in hiv resistance to protease inhibitors |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185719/ https://www.ncbi.nlm.nih.gov/pubmed/21994687 http://dx.doi.org/10.3390/v2071411 |
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