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Cyclophilin A enables specific HIV-1 Tat palmitoylation and accumulation in uninfected cells

Author

Listed:
  • Christophe Chopard

    (Université de Montpellier-CNRS)

  • Phuoc Bao Viet Tong

    (Université de Montpellier-CNRS)

  • Petra Tóth

    (5 rue Blaise Pascal)

  • Malvina Schatz

    (Université de Montpellier-CNRS)

  • Hocine Yezid

    (Université de Montpellier-CNRS)

  • Solène Debaisieux

    (Université de Montpellier-CNRS)

  • Clément Mettling

    (141 Rue de la Cardonille)

  • Antoine Gross

    (Université de Montpellier-CNRS)

  • Martine Pugnière

    (208 Rue des Apothicaires)

  • Annie Tu

    (5 rue Blaise Pascal)

  • Jean-Marc Strub

    (Université de Strasbourg)

  • Jean-Michel Mesnard

    (Université de Montpellier-CNRS)

  • Nicolas Vitale

    (5 rue Blaise Pascal
    INSERM)

  • Bruno Beaumelle

    (Université de Montpellier-CNRS)

Abstract

Most HIV-1 Tat is unconventionally secreted by infected cells following Tat interaction with phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2) at the plasma membrane. Extracellular Tat is endocytosed by uninfected cells before escaping from endosomes to reach the cytosol and bind PI(4,5)P2. It is not clear whether and how incoming Tat concentrates in uninfected cells. Here we show that, in uninfected cells, the S-acyl transferase DHHC-20 together with the prolylisomerases cyclophilin A (CypA) and FKBP12 palmitoylate Tat on Cys31 thereby increasing Tat affinity for PI(4,5)P2. In infected cells, CypA is bound by HIV-1 Gag, resulting in its encapsidation and CypA depletion from cells. Because of the lack of this essential cofactor, Tat is not palmitoylated in infected cells but strongly secreted. Hence, Tat palmitoylation specifically takes place in uninfected cells. Moreover, palmitoylation is required for Tat to accumulate at the plasma membrane and affect PI(4,5)P2-dependent membrane traffic such as phagocytosis and neurosecretion.

Suggested Citation

  • Christophe Chopard & Phuoc Bao Viet Tong & Petra Tóth & Malvina Schatz & Hocine Yezid & Solène Debaisieux & Clément Mettling & Antoine Gross & Martine Pugnière & Annie Tu & Jean-Marc Strub & Jean-Mich, 2018. "Cyclophilin A enables specific HIV-1 Tat palmitoylation and accumulation in uninfected cells," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04674-y
    DOI: 10.1038/s41467-018-04674-y
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