XTT formazan widely used to detect cell viability inhibits HIV type 1 infectionin Vitro by targeting gp41

Qian Zhao, Justin T. Ernst, Andrew Hamilton, Asim K. Debnath, Shibo Jiang

Research output: Contribution to journalArticle

Abstract

XTT can be metabolically reduced by mitochondrial dehydrogenase in viable cells to a water-soluble formazan product. Thus XTT has been widely used to evaluate cell viability and to screen anti-HIV agents and the cytotoxicity of these agents. The present studies demonstrated that XTT formazan derived from XTT in cell culture significantly inhibits the fusion of HIV-1-infected cells with uninfected cells. Synthetic XTT formazan effectively inhibited the replication of laboratory-adapted and primary HIV-1 isolates and cell-to-cell fusion with low cytotoxicity. It blocks the six-helix bundle formation between peptides derived from the N- and C-terminal heptad repeat regions of the gp41 ectodomain (designated N- and C-peptides, respectively). Analysis by a computer-aided docking program indicates that XTT formazan may bind to the highly conserved hydrophobic pocket on the surface of the central trimeric coiled coil of gp41. These results suggest that XTT formazan inhibits HIV-1 entry by targeting the α-helical coiled-coil domain of gp41. This small molecular nonpeptide antiviral compound can be used as a lead for designing more effective HIV-1 entry inhibitors targeting the fusion stage of HIV-1 infection. But because XTT formazan itself has anti-HIV-1 activity, caution should be exercised when XTT is used to evaluate HIV-1 infectivity.

Original languageEnglish (US)
Pages (from-to)989-997
Number of pages9
JournalAIDS Research and Human Retroviruses
Volume18
Issue number14
DOIs
StatePublished - 2002

Fingerprint

HIV-1
Cell Survival
HIV Fusion Inhibitors
Formazans
Anti-HIV Agents
Terminal Repeat Sequences
Cell Fusion
C-Peptide
1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan
HIV Infections
Antiviral Agents
Oxidoreductases
Cell Culture Techniques
Peptides
Water

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

XTT formazan widely used to detect cell viability inhibits HIV type 1 infectionin Vitro by targeting gp41. / Zhao, Qian; Ernst, Justin T.; Hamilton, Andrew; Debnath, Asim K.; Jiang, Shibo.

In: AIDS Research and Human Retroviruses, Vol. 18, No. 14, 2002, p. 989-997.

Research output: Contribution to journalArticle

Zhao, Qian ; Ernst, Justin T. ; Hamilton, Andrew ; Debnath, Asim K. ; Jiang, Shibo. / XTT formazan widely used to detect cell viability inhibits HIV type 1 infectionin Vitro by targeting gp41. In: AIDS Research and Human Retroviruses. 2002 ; Vol. 18, No. 14. pp. 989-997.
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