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Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021) 总被引:1,自引:0,他引:1
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Delaunay C Brun-Vézinet F Landman R Collin G Peytavin G Trylesinski A Flandre P Miller M Descamps D 《Journal of virology》2005,79(15):9572-9578
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Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1
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The relative replicative fitness of human immunodeficiency virus type 1 (HIV-1) mutants selected by different protease inhibitors (PIs) in vivo was determined. Each mutant was compared to wild type (WT), NL4-3, in the absence of drugs by several methods, including clonal genotyping of cultures infected with two competing viral variants, kinetics of viral antigen production, and viral infectivity/virion particle ratios. A nelfinavir-selected protease D30N substitution substantially decreased replicative capacity relative to WT, while a saquinavir-selected L90M substitution moderately decreased fitness. The D30N mutant virus was also outcompeted by the L90M mutant in the absence of drugs. A major natural polymorphism of the HIV-1 protease, L63P, compensated well for the impairment of fitness caused by L90M but only slightly improved the fitness of D30N. Multiply substituted indinavir-selected mutants M46I/L63P/V82T/I84V and L10R/M46I/L63P/V82T/I84V were just as fit as WT. These results indicate that the mutations which are usually initially selected by nelfinavir and saquinavir, D30N and L90M, respectively, impair fitness. However, additional mutations may improve the replicative capacity of these and other drug-resistant mutants. Hypotheses based on the greater fitness impairment of the nelfinavir-selected D30N mutant are suggested to explain observations that prolonged responses to delayed salvage regimens, including alternate PIs, may be relatively common after nelfinavir failure. 相似文献
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Quantification of the effects on viral DNA synthesis of reverse transcriptase mutations conferring human immunodeficiency virus type 1 resistance to nucleoside analogues
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Bouchonnet F Dam E Mammano F de Soultrait V Henneré G Benech H Clavel F Hance AJ 《Journal of virology》2005,79(2):812-822
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Gao L Hanson MN Balakrishnan M Boyer PL Roques BP Hughes SH Kim B Bambara RA 《The Journal of biological chemistry》2008,283(14):9196-9205
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Knoepfel SA Salisch NC Huelsmann PM Rauch P Walter H Metzner KJ 《Journal of virology》2008,82(13):6536-6545