CpG Oligodeoxynucleotides Activate HIV Replication in Latently Infected Human T Cells

Scheller, Carsten; Ullrich, Anett; McPherson, Kirsty; Hefele, Barbara; Knöferle, Johanna; Lamla, Stefan; Olbrich, Anke R. M.; Stocker, Hartmut; Arastéh, Keikawus; Meulen, Volker ter; Rethwilm, Axel; Koutsilieri, Eleni; Dittmer, Ulf

doi:10.1074/jbc.m311609200

Cited by 50 publications

(36 citation statements)

References 49 publications

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“…There are a number of potential explanations for the inability of CpG-A to prevent SIV transmission, including the possibility that a suboptimal dose or administration schedule was have on viral replication, CpG ODN can directly increase HIV replication in latently infected TLR9 ϩ human T-cell lines by stimulating NF-B activity and viral gene expression (70).…”

Section: Discussionmentioning

confidence: 99%

The Toll-Like Receptor 7 (TLR7) Agonist, Imiquimod, and the TLR9 Agonist, CpG ODN, Induce Antiviral Cytokines and Chemokines but Do Not Prevent Vaginal Transmission of Simian Immunodeficiency Virus When Applied Intravaginally to Rhesus Macaques

Wang

Abel²,

Lantz³

et al. 2005

J Virol

120

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The initial host response to viral infection occurs after؉ T cells, DC, and beta-chemokine-secreting cells. After vaginal SIV inoculation, all TLR agonist-treated animals became infected and had plasma vRNA levels that were higher than those of control monkeys. We conclude that induction of mucosal innate immunity including an IFN-␣ response is not sufficient to prevent sexual transmission of human immunodeficiency virus.

show abstract

Section: Discussionmentioning

confidence: 99%

The Toll-Like Receptor 7 (TLR7) Agonist, Imiquimod, and the TLR9 Agonist, CpG ODN, Induce Antiviral Cytokines and Chemokines but Do Not Prevent Vaginal Transmission of Simian Immunodeficiency Virus When Applied Intravaginally to Rhesus Macaques

Wang

Abel²,

Lantz³

et al. 2005

J Virol

120

View full text Add to dashboard Cite

show abstract

“…Notably, other TLR agonists, such as TLR2, 4, and 9 agonists, may be beneficial for activation of latently infected cells (51)(52)(53). Combination of TLR agonists that target distinct cellular lymphoid subsets, based on their TLR-expression pattern, might even be superior for eradicating latently infected cells to one TLR agonist alone.…”

Section: Discussionmentioning

confidence: 99%

TLR8 Activates HIV from Latently Infected Cells of Myeloid-Monocytic Origin Directly via the MAPK Pathway and from Latently Infected CD4+ T Cells Indirectly via TNF-α

Schlaepfer

Speck

2011

The Journal of Immunology

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We previously showed that the TLR7/8 agonist, R-848, activated HIV from cells of myeloid-monocytic origin. In this work, we show that this effect was solely due to triggering TLR8 and that NF-κB was involved in the TLR8-mediated activation of HIV from latently infected cells of myeloid-monocytic origin. Inhibition of Erk1/2 or p38α resulted in attenuation of TLR8-mediated activation of NF-κB. Western blots confirmed that TLR8 triggering activated Erk1/2 and p38α but, surprisingly, not JNK. Although the Erk1/2 inhibitors resulted in a less attenuated TLR8-mediated NF-κB response than did p38α inhibitors, they had a more pronounced effect on blocking TLR8-mediated HIV replication, indicating that other transcription factors controlled by Erk1/2 are involved in TLR8-mediated HIV activation from latently infected cells. TNF-α, which was secreted subsequent to TLR8 triggering, contributed to the activation of HIV from the latently infected cells in an autocrine manner, revealing a bimodal mechanism by which the effect of TLR8 triggering can be sustained. We also found that TNF-α secreted by myeloid dendritic cells acted in a paracrine manner in the activation of HIV from neighboring latently infected CD4+ T cells, which do not express TLR8. Notably, monocytes from highly active antiretroviral therapy-treated HIV+ patients with suppressed HIV RNA showed a robust TNF-α secretion in response to TLR8 agonists, pointing to a functional TLR8 signaling axis in HIV infection. Thus, triggering TLR8 represents a very promising strategy for attacking the silent HIV from its reservoir in HIV+ patients treated successfully with highly active antiretroviral therapy.

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“…The data are the means (ϮSD) from four independent experiments using different donors. 134,139,161). Therefore, the use of the synthetic TLR2 ligand PAM3CSK4 recapitulates the contribution of other STI cofactors on HIV-1 replication in macrophages.…”

Section: Nr Ligands Inhibit Hiv-1 Replication In Primary Macrophagesmentioning

confidence: 99%

“…Second, STIs cause inflammation that leads to the recruitment of immune cells to the site of inflammation, thereby increasing the size of the HIV-1 target cell population (88,128,136). Third, STIs promote a favorable local environment for HIV-1 replication both by directly activating HIV-1 target cells and by inducing the release of cytokines that favor virus replication through the engagement of Toll-like receptors (TLRs) and other innate immune sensors in cells present in the mucosa (9,10,37,57,75,122,134,145,146,161).…”

mentioning

confidence: 99%

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

Hanley

Viglianti

2011

J Virol

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CpG Oligodeoxynucleotides Activate HIV Replication in Latently Infected Human T Cells

Abstract: CpG oligodeoxynucleotides (CpG ODNs)

Cited by 50 publications

References 49 publications

The Toll-Like Receptor 7 (TLR7) Agonist, Imiquimod, and the TLR9 Agonist, CpG ODN, Induce Antiviral Cytokines and Chemokines but Do Not Prevent Vaginal Transmission of Simian Immunodeficiency Virus When Applied Intravaginally to Rhesus Macaques

The Toll-Like Receptor 7 (TLR7) Agonist, Imiquimod, and the TLR9 Agonist, CpG ODN, Induce Antiviral Cytokines and Chemokines but Do Not Prevent Vaginal Transmission of Simian Immunodeficiency Virus When Applied Intravaginally to Rhesus Macaques

TLR8 Activates HIV from Latently Infected Cells of Myeloid-Monocytic Origin Directly via the MAPK Pathway and from Latently Infected CD4+ T Cells Indirectly via TNF-α

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

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