HIV-1 resistance to the gp41-dependent fusion inhibitor C-34

Mercedes Armand-Ugón, Arantxa Gutiérrez, Bonaventura Clotet, José A. Esté

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65 Citations (Scopus)

Abstract

The gp41 subunit of HIV-1 has been recently recognized as a target for antiviral therapy. C-34 is a peptide that mimics the heptad repeat 2 in the ectodomain of gp41. Here, we describe two HIV-1 strains selected after 5 and 17 passages in culture with increasing concentrations of C-34 (breakthrough concentration of 10μg/ml). The HXB2-derived strain was more than 1000-fold resistant and contained a V38E mutation in the gp41 coding DNA sequence. The NL4-3-derived strain was more than 500-fold resistant and contained a L33S mutation in gp41. No cross-resistance to the RT inhibitor AZT, the HIV binding inhibitor dextran sulfate (DS), or the chemokine receptor antagonist ALX-40-4C was detected. These data indicate that HIV-1 can overcome C-34 inhibition through mutations at residues not involved in the formation of the hydrophobic cavity of gp41. © 2003 Elsevier Science B.V. All rights reserved.
Original languageEnglish
Pages (from-to)137-142
JournalAntiviral Research
Volume59
Issue number2
DOIs
Publication statusPublished - 1 Jul 2003

Keywords

  • Fusion inhibitor
  • gp41
  • Heptad repeat
  • HIV-1
  • Resistance

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