Summary Although dendritic cells are among the human cell population best equipped for cell-intrinsic antiviral immune defense, they seem highly susceptible to infection with Zika Virus (ZIKV). Using highly-purified myeloid dendritic cells isolated from individuals with naturally-acquired acute infection, we here show that ZIKV induces profound perturbations of transcriptional signatures relative to healthy donors. Interestingly, we noted a remarkable downregulation of antiviral Interferon-stimulated genes and innate immune sensors, suggesting that ZIKV can actively suppress Interferon-dependent immune responses. In contrast, several host factors known to support ZIKV infection were strongly upregulated during natural ZIKV infection; these transcripts included AXL, the main entry receptor for ZIKV, SOCS3, a negative regulator of ISG expression, and IDO-1, a recognized inducer of regulatory T cell responses. Thus, during in vivo infection, ZIKV can transform the transcriptome of dendritic cells in favor of the virus to render these cells highly conducive to ZIKV infection.

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV – RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

These data suggest that the reduction of viral reservoir cells during treatment with IFN-α is primarily attributable to antiviral activities of NK cells.

Objective(s) To assess the frequency and function of HIV-1-specific HLA-G+ CD8 T cells in HIV-1 controllers and progressors. Design We performed an observational cross-sectional cohort analysis in untreated (n=47) and treated (n=17) HIV-1 patients with different rates of disease progression and n=14 healthy individuals. Methods We evaluated the frequency, the proportion and the function of total and virus-specific HLA-G+ CD8 T cells by tetramer or intracellular cytokine staining, followed by flow cytometric analysis. Cytokine secretion of sorted CD8 T cell subsets was evaluated by Luminex assays. Results The proportion and the absolute frequency of HLA-G+ HIV-1-specific CD8 T cells were directly associated with CD4 T cell counts and inversely correlated with viral loads, while total or HLA-G-negative HIV-1-specific CD8 T cells were not. In functional assays, HLA-G+ CD8 T cells from HIV-1-negative individuals had higher abilities to produce the antiviral CCR5 ligands MIP-1β, MIP-1α and Rantes. Conclusions HLA-G+ HIV-1-specific CD8 T cells may represent a previously-unrecognized correlate of HIV-1 immune control.

No abstract