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

Carmen Sánchez-Jiménez, Isabel Olivares, Ana Isabel de Ávila Lucas, Víctor Toledano, Mónica Gutiérrez-Rivas, Ramón Lorenzo-Redondo, Ana Grande-Pérez, Esteban Domingo, Cecilio López-Galíndez*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)147-153
Number of pages7
JournalVirology
Volume424
Issue number2
DOIs
StatePublished - Mar 15 2012

Keywords

  • 2 ,2 -difluoro-2 -deoxycytidine (gemcitabine)
  • 5-fluorouracil (5-FU)
  • 5-hydroxy-2 -deoxycytidine (5-OHdC)
  • HIV-1
  • HIV-1 persistent cell line
  • Lethal mutagenesis
  • Nucleoside analogs
  • Viral replication

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Sánchez-Jiménez, C., Olivares, I., de Ávila Lucas, A. I., Toledano, V., Gutiérrez-Rivas, M., Lorenzo-Redondo, R., Grande-Pérez, A., Domingo, E., & López-Galíndez, C. (2012). Mutagen-mediated enhancement of HIV-1 replication in persistently infected cells. Virology, 424(2), 147-153. https://doi.org/10.1016/j.virol.2011.12.016