Homeostatically maintained resting naive CD4+ T cells resist latent HIV reactivation

Yasuko Tsunetsugu-Yokota, Mie Kobayahi-Ishihara, Yamato Wada, Kazutaka Terahara, Haruko Takeyama, Ai Kawana-Tachikawa, Kenzo Tokunaga, Makoto Yamagishi, Javier P. Martinez, Andreas Meyerhans

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Homeostatic proliferation (HSP) is a major mechanism by which long-lived naïve and memory CD4+ T cells are maintained in vivo and suggested to contribute to the persistence of the latent HIV-1 reservoir. However, while many in vitro latency models rely on CD4+ T cells that were initially differentiated via T-cell receptor (TCR) stimulation into memory/effector cells, latent infection of naïve resting CD4+ T cells maintained under HSP conditions has not been fully addressed. Here, we describe an in vitro HSP culture system utilizing the cytokines IL-7 and IL-15 that allows studying latency in naïve resting CD4+ T cells. CD4+ T cells isolated from several healthy donors were infected with HIV pseudotypes expressing GFP and cultured under HSP conditions or TCR conditions as control. Cell proliferation, phenotype, and GFP expression were analyzed by flow cytometry. RNA expression was quantified by qRT-PCR. Under HSP culture conditions, latently HIV-1 infected naïve cells are in part maintained in the non-dividing (= resting) state. Although a few HIV-1 provirus+ cells were present in these resting GFP negative cells, the estimated level of GFP transcripts per infected cell seems to indicate a block at the post-transcriptional level. Interestingly, neither TCR nor the prototypic HDAC inhibitor SAHA were able to reactivate HIV-1 provirus from these cells. This lack of reactivation was not due to methylation of the HIV LTR. These results point to a mechanism of HIV control in HSP-cultured resting naïve CD4+ T cells that may be distinct from that in TCR-stimulated memory/effector T cells.

    Original languageEnglish
    Article number1944
    JournalFrontiers in Microbiology
    Volume7
    Issue numberDEC
    DOIs
    Publication statusPublished - 2016

    Fingerprint

    HIV
    T-Lymphocytes
    T-Cell Antigen Receptor
    HIV-1
    Proviruses
    Interleukin-15
    Interleukin-7
    Histone Deacetylase Inhibitors
    Methylation
    Flow Cytometry
    Cell Proliferation
    RNA
    Cytokines
    Phenotype
    Polymerase Chain Reaction
    Infection
    In Vitro Techniques

    Keywords

    • Cytokines
    • HIV
    • Homeostatic proliferation
    • Latency
    • Naïve CD4 T cells

    ASJC Scopus subject areas

    • Microbiology
    • Microbiology (medical)

    Cite this

    Tsunetsugu-Yokota, Y., Kobayahi-Ishihara, M., Wada, Y., Terahara, K., Takeyama, H., Kawana-Tachikawa, A., ... Meyerhans, A. (2016). Homeostatically maintained resting naive CD4+ T cells resist latent HIV reactivation. Frontiers in Microbiology, 7(DEC), [1944]. https://doi.org/10.3389/fmicb.2016.01944

    Homeostatically maintained resting naive CD4+ T cells resist latent HIV reactivation. / Tsunetsugu-Yokota, Yasuko; Kobayahi-Ishihara, Mie; Wada, Yamato; Terahara, Kazutaka; Takeyama, Haruko; Kawana-Tachikawa, Ai; Tokunaga, Kenzo; Yamagishi, Makoto; Martinez, Javier P.; Meyerhans, Andreas.

    In: Frontiers in Microbiology, Vol. 7, No. DEC, 1944, 2016.

    Research output: Contribution to journalArticle

    Tsunetsugu-Yokota, Y, Kobayahi-Ishihara, M, Wada, Y, Terahara, K, Takeyama, H, Kawana-Tachikawa, A, Tokunaga, K, Yamagishi, M, Martinez, JP & Meyerhans, A 2016, 'Homeostatically maintained resting naive CD4+ T cells resist latent HIV reactivation', Frontiers in Microbiology, vol. 7, no. DEC, 1944. https://doi.org/10.3389/fmicb.2016.01944
    Tsunetsugu-Yokota Y, Kobayahi-Ishihara M, Wada Y, Terahara K, Takeyama H, Kawana-Tachikawa A et al. Homeostatically maintained resting naive CD4+ T cells resist latent HIV reactivation. Frontiers in Microbiology. 2016;7(DEC). 1944. https://doi.org/10.3389/fmicb.2016.01944
    Tsunetsugu-Yokota, Yasuko ; Kobayahi-Ishihara, Mie ; Wada, Yamato ; Terahara, Kazutaka ; Takeyama, Haruko ; Kawana-Tachikawa, Ai ; Tokunaga, Kenzo ; Yamagishi, Makoto ; Martinez, Javier P. ; Meyerhans, Andreas. / Homeostatically maintained resting naive CD4+ T cells resist latent HIV reactivation. In: Frontiers in Microbiology. 2016 ; Vol. 7, No. DEC.
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    AU - Wada, Yamato

    AU - Terahara, Kazutaka

    AU - Takeyama, Haruko

    AU - Kawana-Tachikawa, Ai

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    AU - Yamagishi, Makoto

    AU - Martinez, Javier P.

    AU - Meyerhans, Andreas

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