Indirubin 3′-Monoxime, from a Chinese Traditional Herbal Formula, Suppresses Viremia in Humanized Mice Infected with Multidrug-Resistant HIV

Heredia, Alonso; Natesan, Senthilkumar; Le, Nhut; Medina‐Moreno, Sandra; Zapata, Juan Carlos; Reitz, Marvin S.; Bryant, Joseph; Redfield, Robert

doi:10.1089/aid.2013.0249

Cited by 10 publications

(17 citation statements)

References 27 publications

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“…There were no improvements in frequency of this subset in animals inoculated with expanded cells and/or antibody compared with untreated groups by day 24, which was the last day of our experiments. Along with depletion of target cells, the CD4:CD8 ratio [21] was inverted in all infected groups irrespective of treatment (Figure 2). The levels of viral replication measured by detecting p24 antigen in plasma samples showed comparable p24 in all infected groups at most time points, with a peak replication observed in most animals at day 7.…”

Section: Resultsmentioning

confidence: 93%

Adoptive Transfer of Aminobisphonate-Expanded Vγ9Vδ2+ T Cells does not Control HIV Replication in a Humanized Mouse Model

Poonia

2016

Immunotherapy

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Aim: Vγ9Vδ2 γδ T cells have effector potential against several cancers and infectious agents. Whether these cells control HIV replication was tested in humanized mouse model. Methods: NOD SCID gamma mice engrafted with human peripheral blood mononuclear cells (PBMCs) and infected with HIVBAL were treated with zoledronate-expanded Vγ9Vδ2 T cells either alone or in combination with an anti-HIV envelope antibody b12. Results: Severe depletion of CD4+CCR5+ T cells was observed in PBMCs of all infected mice. HIV plasma p24 levels were comparable in all infected groups with no decrease in plasma viremia achieved by adoptive transfer of cells. Conclusion: Autologous transfer of ex vivo expanded Vγ9Vδ2 T cells may not be a successful treatment choice for controlling HIV replication in vivo.

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Section: Resultsmentioning

confidence: 93%

Adoptive Transfer of Aminobisphonate-Expanded Vγ9Vδ2+ T Cells does not Control HIV Replication in a Humanized Mouse Model

Poonia

2016

Immunotherapy

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“…More recently, IM was shown to reduce viral replication of two multidrug-resistant HIV reverse transcriptase (RT) molecular clones in humanized mice (Heredia et al 2014). …”

Section: Inhibition Of P-tefb An Essential Cellular Complex For Himentioning

confidence: 99%

Targeting HIV Transcription: The Quest for a Functional Cure

Mousseau

Mediouni

Valente

2015

The Future of HIV-1 Therapeutics

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Antiretroviral therapy (ART) potently suppresses HIV-1 replication, but the virus persists in quiescent infected CD4+T cells as a latent integrated provirus, and patients must indefinitely remain on therapy. If ART is terminated, these integrated proviruses can reactivate, driving new rounds of infection. A functional cure for HIV requires eliminating low-level ongoing viral replication that persists in certain tissue sanctuaries and preventing viral reactivation. The HIV Tat protein plays an essential role in HIV transcription by recruiting the kinase activity of the P-TEFb complex to the viral mRNA’s stem–bulge–loop structure, TAR, activating transcriptional elongation. Because the Tat-mediated transactivation cascade is critical for robust HIV replication, the Tat/TAR/P-TEFb complex is one of the most attractive targets for drug development. Importantly, compounds that interfere with transcription could impair viral reactivation, low-level ongoing replication, and replenishment of the latent reservoir, thereby reducing the size of the latent reservoir pool. Here, we discuss the potential importance of transcriptional inhibitors in the treatment of latent HIV-1 disease and review recent findings on targeting Tat, TAR, and P-TEFb individually or as part of a complex. Finally, we discuss the impact of extracellular Tat in HIV-associated neurocognitive disorders and cancers.

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“…Figure 4 presents results from two representative experiments. By standard quantitative RT-PCR, 32,43 there was clear evidence of productive infection. HIV-1 RNA was not detectable in noninfected mice (n = 5).…”

Section: (Flsc) Igg1 Inhibition Of Hiv-1 Entry Into Macrophages Is Grmentioning

confidence: 99%

“…Figure 4 shows data from days 0, 7, 12, 18, 24, and 28 in both noninfected and infected mice, obtained by flow cytometry. 32,43 Both CD4 + (Fig. 4A) and CCR5 + cells from within the CD4 + T cell population (Fig.…”

Section: (Flsc) Igg1 Inhibition Of Hiv-1 Entry Into Macrophages Is Grmentioning

confidence: 99%

Full Length Single Chain Fc Protein (FLSC IgG1) as a Potent Antiviral Therapy Candidate: Implications forIn VivoStudies

Latinovic

Medina‐Moreno

Schneider

et al. 2016

AIDS Research and Human Retroviruses

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We have previously shown that FLSC, a chimeric protein containing HIV-1 BAL gp120 and the D1 and D2 domains of human CD4, blocks the binding and entry of HIV-1 into target cells by occluding CCR5, the major HIV-1 coreceptor. In an effort to improve the antiviral potential of FLSC, we fused it with the hinge-C H 2-C H 3 region of human IgG1. The IgG moiety should increase both the affinity and stability in vivo of FLSC, due to the resultant bivalency and an extended serum half-life, thereby increasing its antiviral potency. We previously showed that (FLSC) IgG1 indeed had greater antiviral activity against T cell infections. Here we extend these results to macrophages, for which (FLSC) IgG1 has a more potent antiviral activity than FLSC alone, due in part to its higher binding affinity for CCR5. We also test both compounds in a relevant humanized mouse model and show that, as anticipated, the IgG1 moiety confers a greatly extended half-life. These data, taken together with previous results, suggest potential clinical utility for (FLSC) IgG1 and support further developmental work toward eventual clinical trials.

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Indirubin 3′-Monoxime, from a Chinese Traditional Herbal Formula, Suppresses Viremia in Humanized Mice Infected with Multidrug-Resistant HIV

Cited by 10 publications

References 27 publications

Adoptive Transfer of Aminobisphonate-Expanded Vγ9Vδ2+ T Cells does not Control HIV Replication in a Humanized Mouse Model

Adoptive Transfer of Aminobisphonate-Expanded Vγ9Vδ2+ T Cells does not Control HIV Replication in a Humanized Mouse Model

Targeting HIV Transcription: The Quest for a Functional Cure

Full Length Single Chain Fc Protein (FLSC IgG1) as a Potent Antiviral Therapy Candidate: Implications forIn VivoStudies

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