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Mutagen-mediated enhancement of HIV-1 replication in persistently infected cells.

Tipo: Artículo de revista
Referencia 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 C
Autores pertenecientes a este Departamento: Ana Grande Pérez
Revista: Virology
Año de publicación: 2012
Volumen: 424
Páginas: 147-153
Editorial: Elsevier
Palabras clave: 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.

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