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

AuthorsSánchez-Jiménez, Carmen ; Olivares, Isabel; Ávila Lucas, Ana Isabel de ; Toledano, Víctor; Gutiérrez-Rivas, Mónica; Lorenzo-Redondo, Ramón; Grande-Pérez, Ana ; Domingo, Esteban ; López-Galíndez, Cecilio
KeywordsLethal 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)
Issue Date2012
PublisherAcademic Press
CitationVirology 424: 147- 153 (2012)
AbstractLethal 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. © 2011 Elsevier Inc.
Identifiersdoi: 10.1016/j.virol.2011.12.016
issn: 0042-6822
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