Broadly Neutralizing Antibody VRC01 Prevents HIV-1 Transmission from Plasmacytoid Dendritic Cells to CD4 T Lymphocytes

Su, Bin; Lederle, Alexandre; Laumond, Géraldine; Ducloy, Camille; Schmidt, Sylvie; Decoville, Thomas; Moog, Christiane

doi:10.1128/jvi.01748-14

Cited by 14 publications

(12 citation statements)

References 65 publications

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“…To test how Vpr in HIV-1 particles affects activation of pDCs, we utilized the TLR7/8 agonist, R848, to activate pDCs in the presence of HIV-1 or HIV-1ΔVpr viruses. As shown in Figure 3A, cell-free HIV-1 alone at the used dose failed to activate pDCs as previously reported (Bloch et al, 2014;Su et al, 2014). However, wild type HIV-1 but not HIV-1ΔVpr viruses significantly reduced IFN-α induction by R848.…”

Section: Virion-associated Vpr Modulates Ifn-i Induction In Pdcs Via supporting

confidence: 84%

HIV-1 Vpr Degrades TET2 to Suppress IRF7 and Interferon Expression in Plasmacytoid Dendritic Cells

Wang

Tsao

et al. 2019

Preprint

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Plasmacytoid dendritic cells (pDCs) are the major source of type I interferons (IFN-I) in rapid response to viral infections, with constitutive expression of interferon regulatory factor 7 (IRF7). HIV-1 expresses several accessory proteins to counteract specific IFN-induced host restriction factors. As one abundant virion-associated protein, HIV-1 Vpr remains enigmatic in enhancing HIV-1 infection via unclear mechanisms. Here we report that Vpr impaired IFN-I induction in pDCs to enhance HIV-1 replication in CD4+ T cells. Blockade of IFN-I signaling abrogated the effect of Vpr on HIV-1 replication. Virion-associated Vpr suppressed IFN-I induction in pDC by TLR7 agonists. Modulation of IFN-I induction by Vpr was genetically dependent on its activity of TET2 degradation. We further demonstrate that Vpr-mediated TET2 degradation reduced expression of IRF7 in pDCs. Finally, degradation of TET2 in pDCs by Vpr reduced the demethylation level of the IRF7 promoter via CXXC5-dependent recruitment. We conclude that HIV-1 Vpr functions to promote HIV-1 replication by suppressing TET2-dependent IRF7 expression and IFN-I induction in pDCs. The Vpr-TET2-IRF7 axis provides a novel therapeutic target to control HIV-1 infection.

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Section: Virion-associated Vpr Modulates Ifn-i Induction In Pdcs Via supporting

confidence: 84%

HIV-1 Vpr Degrades TET2 to Suppress IRF7 and Interferon Expression in Plasmacytoid Dendritic Cells

Wang

Tsao

et al. 2019

Preprint

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“…GraphPad Prism 5.04 software (GraphPad, San Diego, CA) was used for all statistical analyses. found that the expression of CD83 and CD86 17 was increased in the presence of HIV-1 BaL and HIV-1 BX11 17 when DCs were cocultured with CD4 + T lymphocytes, and that these maturation markers were further increased by the addition of bNAb 4E10 (Fig. 1D).…”

Section: Fig 1 Inhibition Of Hiv-1 Cell-free and Cell-to-cell Transmentioning

confidence: 89%

“…A similar bNAb-mediated inhibition was also observed with HIV-1 BaL or a transmitted/founder (T/F) primary isolate HIV-1 Bx11 either transferred from pDCs or directly infecting CD4 + T cells. 17 Noteworthy, using the TZM-bl assay (NIH, Bethesda, MD), 18 a 10-fold more efficient inhibition of the cell-free HIV-1 BaL infection was measured for bNAb VRC01 whereas 4E10 performed poorly against this primary isolate on TZM-bl cells ( Fig. 1B and C, black column).…”

mentioning

confidence: 98%

Short Communication: Exploring Antibody Potential as Prophylactic/Therapeutic Strategies for Prevention of Early Mucosal HIV-1 Infection

SuBin

PeressinMaryse

DucloyCamille

et al. 2015

AIDS Research and Human Retroviruses

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Mucosal tissues are the predominant sites for genital HIV-1 transmission. We investigated the mechanisms by which broadly neutralizing antibodies (bNAbs) inhibit HIV-1 replication in a coculture model including primary mucosal dendritic cells (DCs), such as Langerhans cells, interstitial dendritic cells, and CD4+ T lymphocytes. We show that bNAbs efficiently prevent HIV-1 infection by inhibiting HIV-1 transmission to CD4 + T lymphocytes. This inhibition of cell-to-cell transmission was observed with equal potency as the inhibition of cell-free infection of primary CD4 + T lymphocytes. In addition, a decrease in HIV-1 replication in DCs and the induction of DC maturation were detected. This additional inhibition was Fc mediated as it was blocked by the use of specific anti-FccR monoclonal Abs. The DC maturation by bNAbs during HIV transmission may contribute to mucosal protection. Therefore, multiple antibody-mediated inhibitory functions should be combined for the improvement of future preventive/therapeutic strategies to cure HIV.

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“…Bin Su et al (Inserm, France) reported that VRC01 bNAb prevented HIV-1 transmission from plasmacytoid dendritic cells (pDCs) to autologous CD4 + T cells in culture as well as cell-free viral transmission to CD4 + T cells. 41 As pDCs link innate and adaptive immunity and transmit HIV to CD4 + T cells, VRC01 bNAb could be used to prevent viral transmission in patients. Additionally, this bNAb might also be useful as part of shock and kill eradication strategies to recognize HIV Env expression on reactivated infected cells to promote their clearance by antibody-dependent cellular cytotoxicity or other mechanisms 42 analogous to PGT121 above.…”

Section: New Approaches To Kill and Clear Reactivated Latently Infectmentioning

confidence: 99%

Progress Towards an HIV Cure: Update from the 2014 International AIDS Society Symposium

Anderson

Fromentin

Corbelli³

et al. 2015

AIDS Research and Human Retroviruses

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Biomedical research has led to profound advances in the treatment of HIV infection. Combination antiretroviral therapy (ART) now provides the means to readily control viral infection, and people living with HIV who receive timely and effective ART can expect to benefit from a life expectancy comparable to uninfected individuals. Nevertheless, despite effective treatment, ART does not fully restore the immune system and importantly HIV persists indefinitely in latent reservoirs, resulting in the need for life-long treatment. The challenges and limits of life-long treatment have spurred significant scientific interest and global investment into research towards an HIV cure. The International AIDS Society (IAS) 2014 Towards an HIV cure symposium brought together researchers and community to discuss the most recent advances in our understanding of latency and HIV reservoirs, and the clinical approaches towards an HIV cure under current investigation. This report summarizes and reviews some of the major findings discussed during the symposium.

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Broadly Neutralizing Antibody VRC01 Prevents HIV-1 Transmission from Plasmacytoid Dendritic Cells to CD4 T Lymphocytes

Cited by 14 publications

References 65 publications

HIV-1 Vpr Degrades TET2 to Suppress IRF7 and Interferon Expression in Plasmacytoid Dendritic Cells

HIV-1 Vpr Degrades TET2 to Suppress IRF7 and Interferon Expression in Plasmacytoid Dendritic Cells

Short Communication: Exploring Antibody Potential as Prophylactic/Therapeutic Strategies for Prevention of Early Mucosal HIV-1 Infection

Progress Towards an HIV Cure: Update from the 2014 International AIDS Society Symposium

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