Provirus activation plus CD59 blockage triggers antibody-dependent complement-mediated lysis of latently HIV-1-infected cells

Jie Lan, Kai Yang, Daniel Byrd, Ningjie Hu, Tohti Amet, Nicole Shepherd, Mona Desai, Jimin Gao, Samir Gupta, Yongtao Sun, Andy Yu

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Latently HIV-1-infected cells are recognized as the last barrier toward viral eradication and cure. To purge these cells, we combined a provirus stimulant with a blocker of human CD59, a key member of the regulators of complement activation, to trigger Ab-dependent complement-mediated lysis. Provirus stimulants including prostratin and histone deacetylase inhibitors such as romidepsin and suberoylanilide hydroxamic acid activated proviruses in the latently HIV-1-infected T cell line ACH-2 as virion production and viral protein expression on the cell surface were induced. Romidepsin was the most attractive provirus stimulant as it effectively activated proviruses at nanomolar concentrations that can be achieved clinically. Antiretroviral drugs including two protease inhibitors (atazanavir and darunavir) and an RT inhibitor (emtricitabine) did not affect the activity of provirus stimulants in the activation of proviruses. However, saquinavir (a protease inhibitor) markedly suppressed virus production, although it did not affect the percentage of cells expressing viral Env on the cell surface. Provirus-activated ACH-2 cells expressed HIV-1 Env that colocalized with CD59 in lipid rafts on the cell surface, facilitating direct interaction between them. Blockage of CD59 rendered provirus-activated ACH-2 cells and primary human CD4+T cells that were latently infected with HIV-1 sensitive to Ab-dependent complement-mediated lysis by anti-HIV-1 polyclonal Abs or plasma from HIV-1-infected patients. Therefore, a combination of provirus stimulants with regulators of complement activation blockers represents a novel approach to eliminate HIV-1.

Original languageEnglish
Pages (from-to)3577-3589
Number of pages13
JournalJournal of Immunology
Volume193
Issue number7
DOIs
StatePublished - Oct 1 2014

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Proviruses
HIV-1
Antibodies
Complement Activation
Protease Inhibitors
Saquinavir
T-Lymphocytes
Histone Deacetylase Inhibitors
Viral Proteins
Virion
Viruses
Lipids
Cell Line

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Provirus activation plus CD59 blockage triggers antibody-dependent complement-mediated lysis of latently HIV-1-infected cells. / Lan, Jie; Yang, Kai; Byrd, Daniel; Hu, Ningjie; Amet, Tohti; Shepherd, Nicole; Desai, Mona; Gao, Jimin; Gupta, Samir; Sun, Yongtao; Yu, Andy.

In: Journal of Immunology, Vol. 193, No. 7, 01.10.2014, p. 3577-3589.

Research output: Contribution to journalArticle

Lan, Jie ; Yang, Kai ; Byrd, Daniel ; Hu, Ningjie ; Amet, Tohti ; Shepherd, Nicole ; Desai, Mona ; Gao, Jimin ; Gupta, Samir ; Sun, Yongtao ; Yu, Andy. / Provirus activation plus CD59 blockage triggers antibody-dependent complement-mediated lysis of latently HIV-1-infected cells. In: Journal of Immunology. 2014 ; Vol. 193, No. 7. pp. 3577-3589.
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