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STING agonists activate latently infected cells and enhance SIV-specific responses ex vivo in naturally SIV controlled cynomolgus macaques
- Source :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group UK, 2019.
-
Abstract
- To achieve a functional cure for HIV, treatment regimens that eradicate latently HIV-infected cells must be established. For this, many groups have attempted to reactivate latently-infected cells to induce cytopathic effects and/or elicit cytotoxic T lymphocyte (CTL)/NK cell-mediated immune responses to kill these cells. We believe that not only the reactivation of latently-infected cells, but also the induction of strong CTL responses, would be required for this. Here, we used typical immune activators that target pattern recognition receptors (PRRs). For our experimental model, we identified eight SIV-infected cynomolgus monkeys that became natural controllers of viremia. Although plasma viral loads were undetectable, we could measure SIV-DNA by qPCR in peripheral blood mononuclear cells (PBMCs). Using these PBMCs, we screened 10 distinct PRR ligands to measure IFN-α and IFN-γ production. Among these, STING ligands, cGAMP and c-di-AMP, and the TLR7/8 agonist R848 markedly increased cytokine levels. Both R848 and STING ligands could reactivate latently-infected cells in both cynomolgus monkeys and human PBMCs in vitro. Furthermore, c-di-AMP increased the frequency of SIV Gag-specific CD8+ T cells including polyfunctional CD8+ T cells, as compared to that in untreated control or R848-treated cells. Together, STING ligands might be candidates for HIV treatment.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_treatment
Simian Acquired Immunodeficiency Syndrome
lcsh:Medicine
Biology
CD8-Positive T-Lymphocytes
Peripheral blood mononuclear cell
Article
03 medical and health sciences
0302 clinical medicine
Immune system
medicine
Cytotoxic T cell
Animals
lcsh:Science
Multidisciplinary
lcsh:R
Toll-Like Receptors
Imidazoles
virus diseases
Membrane Proteins
Viral Load
Virology
Virus Latency
Sting
CTL
Macaca fascicularis
030104 developmental biology
Cytokine
Leukocytes, Mononuclear
lcsh:Q
Simian Immunodeficiency Virus
Virus Activation
Nucleotides, Cyclic
030217 neurology & neurosurgery
CD8
Ex vivo
Dinucleoside Phosphates
T-Lymphocytes, Cytotoxic
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....d1e470a012539103e4621d753fd79a35