Mutagen-mediated enhancement of HIV-1 replication in persistently infected cells.
Artículo de revistaReferencia Autores:
Sánchez-Jiménez C, Olivares I, de Ávila Lucas AI, Toledano V, Gutiérrez-Rivas M, Lorenzo-Redondo R, Grande-Pérez A, Domingo E, López-Galíndez CAutores pertenecientes a este Departamento: Ana Grande PérezRevista:
VirologyAño de publicación:
HIV-1; Lethal mutagenesis; Viral replication; HIV-1 persistent cell line; Nucleoside analogs; 5-hydroxy-2′-deoxycytidine (5-OHdC); 5-fluorouracil (5-FU); 2′,2′-difluoro-2′-deoxycytidine (gemcitabine)Artículo: [descargar archivo]Abstract:
Lethal mutagenesis, a new antiviral strategy to extinguish virus through elevated mutation rates, was explored in H61-D cells an HIV-1 persistently infected lymphoid cell line. Three mutagenic agents: 5-hydroxy-2′-deoxycytidine (5-OHdC), 5-fluorouracil (5-FU) and 2,2′-difluoro-2′-deoxycytidine (gemcitabine) were used. After 54 passages, treatments with 5-FU and gemcitabine reduced virus infectivity, p24 and RT activity. Treatment with the pyrimidine analog 5-OHdC resulted in increases of p24 production, RT activity and infectivity. Rise in viral replication by 5-OHdC during HIV-1 persistence is in contrast with its inhibitory effect in acute infections. Viral replication enhancement by 5-OHdC was associated with an increase in intracellular HIV-1 RNA mutations. Mechanisms of HIV-1 replication enhancement by 5-OHdC are unknown but some potential factors are discussed. Increase of HIV-1 replication by 5-OHdC cautions against the use, without previous analyses, of mutagenic nucleoside analogs for AIDS treatment.