An HIV-1 215V mutant shows increased phenotypic resistance to d4T.
Human immunodeficiency virus type 1 (HIV-1) viruses with C/S/D/E at 215 codon of the reverse transcriptase (RT) have been associated with the T215Y/F HIV-1 resistant viruses transmission to naïve patients. The uncommon T215V mutation was detected in DNA proviral samples of a treatment-naïve patient. Virus T215V was obtained after cloning the patient-RT into a molecular clone. Wild-type (T215) and resistant (T215F) clones, were obtained in T215V clone by "in vitro" site-directed mutagenesis. Phenotypic resistance against AZT, ddI and d4T, replication kinetics and the selection of resistance mutations were estimated "in vitro". The T215V virus replicated as efficiently as the wild-type (T215) without antivirals and in the presence of AZT or ddI. The T215V virus showed higher replicative capacity than the wild-type and a 4.3-fold increase in the IC(50) values in cultures with d4T. Selection of resistance mutations was not observed in viral quasispecies of the T215V virus after serial passages in culture in presence of increasing concentrations of AZT, ddI or d4T. This work demonstrates that the T215V mutation decreases the susceptibility of HIV-1 to d4T, and consequently, it could compromise the response to regimens containing this antiviral.
Pernas
Maria
M
Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera de Pozuelo Km 2, Majadahonda, 28220 Madrid, Spain. mpernas@isciii.es
López-Galíndez
Cecilio
C
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D018119:Stavudine / Q000494:pharmacology*; D014779:Virus Replication
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine