A Mechanistic Overview of Dendritic Cell-Mediated HIV-1
            <i>Trans</i>
            Infection: The Story So Far

Kijewski, Suzanne D. G.; Gummuluru, Suryaram

doi:10.2217/fvl.15.2

Cited by 22 publications

(27 citation statements)

References 121 publications

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“…This passive transfer, also known as “trans-infection” (for a review see [31]), results from transmission of captured viral particles without productive infection, and is the main route used by HIV-1 for spreading to T-cells [32]. Since viral capture is around three-fold higher in LPS-matured DCs (see Fig 4E) and six-fold higher in IFN-α DCs (see Fig 2D) than in IL-4 DCs, we hypothesized that trans-infection might occur preferentially with mature DCs compared to IL-4 DCs.…”

Section: Resultsmentioning

confidence: 99%

Dendritic cell maturation, but not type I interferon exposure, restricts infection by HTLV-1, and viral transmission to T-cells

et al. 2017

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Human T lymphotropic Virus type 1 (HTLV-1) is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Both CD4+ T-cells and dendritic cells (DCs) infected with HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1 infection than autologous primary T-cells, suggesting that DC infection precedes T-cell infection. However, during blood transmission, breast-feeding or sexual transmission, HTLV-1 may encounter different DC subsets present in the blood, the intestinal or genital mucosa respectively. These different contacts may impact HTLV-1 ability to infect DCs and its subsequent transfer to T-cells. Using in vitro monocyte-derived IL-4 DCs, TGF-β DCs and IFN-α DCs that mimic DCs contacting HTLV-1 in vivo, we show here that despite their increased ability to capture HTLV-1 virions, IFN-α DCs restrict HTLV-1 productive infection. Surprisingly, we then demonstrate that it is not due to the antiviral activity of type–I interferon produced by IFN-α DCs, but that it is likely to be linked to a distinct trafficking route of HTLV-1 in IL-4 DCs vs. IFN-α DCs. Finally, we demonstrate that, in contrast to IL-4 DCs, IFN-α DCs are impaired in their capacity to transfer HTLV-1 to CD4 T-cells, both after viral capture and trans-infection and after their productive infection. In conclusion, the nature of the DCs encountered by HTLV-1 upon primo-infection and the viral trafficking route through the vesicular pathway of these cells determine the efficiency of viral transmission to T-cells, which may condition the fate of infection.

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Section: Resultsmentioning

confidence: 99%

Dendritic cell maturation, but not type I interferon exposure, restricts infection by HTLV-1, and viral transmission to T-cells

et al. 2017

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“…We have previously postulated that mature DCs in an inflammatory microenvironment are critical cellular vectors for mediating HIV-1 dissemination by capturing virus, trafficking to lymph nodes and efficiently transferring captured virus to CD4 + T cells (Izquierdo-Useros et al, 2014; Kijewski and Gummuluru, 2015). CD169 is a myeloid cell specific antigen (Crocker et al, 2007) whose expression is positively correlated with viral loads in HIV-1 infected individuals (Rempel et al, 2008; van der Kuyl et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Access of HIV-2 to CD169-dependent dendritic cell-mediated trans infection pathway is attenuated

et al. 2016

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The mechanisms behind the low viral loads and lower mortality rates of HIV-2+ individuals remain unknown. We hypothesized that reduced interaction of HIV-2 with CD169, the primary HIV-1 attachment factor on monocyte-derived dendritic cells (DCs) that targets captured virus particles to the trans infection pathway, contributes to its diminished pathogenic phenotype in vivo. We observed a significant decrease in capture of HIV-2 Gag-eGFP virus-like particles (VLPs) and infectious GFP-containing HIV-2 particles compared to corresponding HIV-1 particles by CD169+ mature DCs. Interestingly, there was decreased co-localization of HIV-2 with HIV-1 Gag at plasma membrane microdomains in virus producer cells which correlated with reduced incorporation of GM3, the CD169 ligand, in HIV-2 virions, and reduction in mature DC-mediated HIV-2 trans infection compared to HIV-1. We conclude that limited interaction of HIV-2 with CD169 diminishes virus access to the mature DC-mediated trans infection pathway and might result in attenuated HIV-2 dissemination in vivo.

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“…These cells seem intrinsically involved in many aspects of HIV-1 pathogenesis and immune defense and can simultaneously act as target cells for HIV-1 replication, as sites for antigen recognition, presentation and immune induction, and as mobile vehicles for HIV-1 particle capture and dissemination [10–12, 13••, 14]. Due to the exquisite rarity of these cells in the peripheral circulation, analyzing primary mDC from HIV-1 controllers tends to be remarkably complex and requires large amounts of available cell samples.…”

Section: Introductionmentioning

confidence: 99%

Dendritic Cell Immune Responses in HIV-1 Controllers

Martín‐Gayo

2017

Curr HIV/AIDS Rep

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Purpose of Review Robust HIV-1-specific CD8 T cell responses are currently regarded as the main correlate of immune defense in rare individuals who achieve natural, drug-free control of HIV-1; however, the mechanisms that support evolution of such powerful immune responses are not well understood. Dendritic cells (DCs) are specialized innate immune cells critical for immune recognition, immune regulation, and immune induction, but their possible contribution to HIV-1 immune defense in controllers remains ill-defined. Recent Findings Recent studies suggest that myeloid DCs from controllers have improved abilities to recognize HIV-1 through cytoplasmic immune sensors, resulting in more potent, cell-intrinsic type I interferon secretion in response to viral infection. This innate immune response may facilitate DC-mediated induction of highly potent antiviral HIV-1-specific T cells. Moreover, protective HLA class I isotypes restricting HIV-1-specific CD8 T cells may influence DC function through specific interactions with innate myelomonocytic MHC class I receptors from the leukocyte immunoglobulin-like receptor family. Summary Bi-directional interactions between dendritic cells and HIV-1-specific T cells may contribute to natural HIV-1 immune control, highlighting the importance of a fine-tuned interplay between innate and adaptive immune activities for effective antiviral immune defense.

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A Mechanistic Overview of Dendritic Cell-Mediated HIV-1 Trans Infection: The Story So Far

Cited by 22 publications

References 121 publications

Dendritic cell maturation, but not type I interferon exposure, restricts infection by HTLV-1, and viral transmission to T-cells

Dendritic cell maturation, but not type I interferon exposure, restricts infection by HTLV-1, and viral transmission to T-cells

Access of HIV-2 to CD169-dependent dendritic cell-mediated trans infection pathway is attenuated

Dendritic Cell Immune Responses in HIV-1 Controllers

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