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dc.contributor.author | Álvarez, Mar | - |
dc.contributor.author | Sebastián-Martín, Alba | - |
dc.contributor.author | García-Marquina, Guillermo | - |
dc.contributor.author | Menéndez-Arias, Luis | - |
dc.date.accessioned | 2018-06-08T11:09:00Z | - |
dc.date.available | 2018-06-08T11:09:00Z | - |
dc.date.issued | 2017-03-23 | - |
dc.identifier | doi: 10.1038/srep44834 | - |
dc.identifier | issn: 2045-2322 | - |
dc.identifier.citation | Scientific Reports 7 (2017) | - |
dc.identifier.uri | http://hdl.handle.net/10261/165983 | - |
dc.description.abstract | Nucleoside reverse transcriptase (RT) inhibitors constitute the backbone of current therapies against human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2, respectively). However, mutational pathways leading to the development of nucleoside analogue resistance are different in both types of HIV. In HIV-2, resistance to all approved nucleoside analogues is conferred by the combination of RT substitutions K65R, Q151M and M184V. Nucleotide incorporation kinetic analyses of mutant and wild-type (WT) HIV-2 RTs show that the triple-mutant has decreased catalytic efficiency due to the presence of M184V. Although similar effects were previously reported for equivalent mutations in HIV-1 RT, the HIV-2 enzymes were catalytically less efficient. Interestingly, in highly divergent HIV-1 RTs, K65R confers several-fold increased accuracy of DNA synthesis. We have determined the intrinsic fidelity of DNA synthesis of WT HIV-2 RT and mutants K65R and K65R/Q151M/M184V. Our results show that those changes in HIV-2 RT have a relatively small impact on nucleotide selectivity. Furthermore, we found that there were less than two-fold differences in error rates obtained with forward mutation assays using mutant and WT HIV-2 RTs. A different conformation of the β3-β4 hairpin loop in HIV-1 and HIV-2 RTs could probably explain the differential effects of K65R. | - |
dc.description.sponsorship | Spanish Ministry of Economy and Competitiveness (BIO2013-48788-C2-1-R). A.S.-M. is a recipient of a predoctoral fellowship of the Spanish Ministry of Education, Culture and Sport (FPU2013-00693). An institutional grant of Fundación Ramón Areces (Madrid, Spain) to the Centro de Biología Molecular “Severo Ochoa” | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isversionof | Publisher's version | - |
dc.rights | openAccess | - |
dc.title | Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1038/srep44834 | - |
dc.date.updated | 2018-06-08T11:09:00Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.rights.license | https://creativecommons.org/licenses/by/4.0/ | - |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | - |
dc.contributor.funder | Fundación Ramón Areces | - |
dc.contributor.funder | Ministerio de Educación, Cultura y Deporte (España) | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/100008054 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003176 | es_ES |
dc.identifier.pmid | 28333133 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.fulltext | With Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
item.openairetype | artículo | - |
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MenéndezAriasL_FidelityOfClasswide.pdf | 809,75 kB | Adobe PDF | Visualizar/Abrir |
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