Project description:Using microRNA array analyses of in vitro HIV-1-infected CD4+ cells, we find that several host microRNAs are significantly up- or downregulated around the time HIV-1 infection peaks in vitro. While microRNA-223 levels were significantly enriched in HIV-1-infected CD4+CD8? PBMCs, microRNA-29a/b, microRNA-155 and microRNA-21 levels were significantly reduced. Based on the potential for microRNA binding sites in a conserved sequence of the Nef-3?-LTR, several host microRNAs potentially could affect HIV-1 gene expression. Among those microRNAs, the microRNA-29 family has seed complementarity in the HIV-1 3?-UTR, but the potential suppressive effect of microRNA-29 on HIV-1 is severely blocked by the secondary structure of the target region. Our data support a possible regulatory circuit at the peak of HIV-1 replication which involves downregulation of microRNA-29, expression of Nef, the apoptosis of host CD4 cells and upregulation of microRNA-223. Time course of HIV infection on CD4 cells
Project description:Using microRNA array analyses of in vitro HIV-1-infected CD4+ cells, we find that several host microRNAs are significantly up- or downregulated around the time HIV-1 infection peaks in vitro. While microRNA-223 levels were significantly enriched in HIV-1-infected CD4+CD8− PBMCs, microRNA-29a/b, microRNA-155 and microRNA-21 levels were significantly reduced. Based on the potential for microRNA binding sites in a conserved sequence of the Nef-3′-LTR, several host microRNAs potentially could affect HIV-1 gene expression. Among those microRNAs, the microRNA-29 family has seed complementarity in the HIV-1 3′-UTR, but the potential suppressive effect of microRNA-29 on HIV-1 is severely blocked by the secondary structure of the target region. Our data support a possible regulatory circuit at the peak of HIV-1 replication which involves downregulation of microRNA-29, expression of Nef, the apoptosis of host CD4 cells and upregulation of microRNA-223.
Project description:We aimed to determine the association between extracellular miRs and HIV infection, and have demonstrated unique expression profile of 29 miRs in HIV+ subjects and 34 miRs in elite controllers as compared to HIV- subjects. Elite HIV+ subjects are those who are HIV+, not on antiretroviral therapy, and with HIV viral load <200 copies/mL.
Project description:To investigate whether and what miRNAs expression might be regulated by HIV-1 challenge, we analyzed the miRNA expression profile of MT4 cells inoculated with HIV-1-GFP for 48h using an array-based miRNA profiling and the infectivity was over 90% by analyzing with flow cytometer.
Project description:This phase I trial studies the side effects and best dose of ibrutinib in treating B-cell non-Hodgkin lymphoma that has returned or does not respond to treatment in patients with human immunodeficiency virus (HIV) infection. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether it is safe for patients with HIV infection to receive ibrutinib while also taking anti-HIV drugs.
Project description:We sought to determine how gene expression changes during the first two years of HIV-1 infection among participants from HIV-1 serodiscordant couple cohorts from sub-Saharan Africa. This study included whole blood samples from 26 participants who did not have HIV-1 at study enrollment, had a steady sexual relationship with a partner with HIV-1 and acquired HIV-1 during follow-up. Most participants had samples from before and after infection.
Project description:CD11c+ Myeloid Dendritic Cells (mDCs) were isolated from the peripheral blood mononuclear cells (PBMCs) of HIV uninfected and HIV infected subjects. The expression of CD11c+ mDCs was accessed to determine how HIV infection may play a role on the expression profiles of these cells. mDCs are known to play a role in antigen presentation, and thus are pivotal in immune sensing and priming of the adaptive immune response. We wanted to see if the change in immune system function during chronic HIV infection may be due to defects in this cell subtype. We used microarray analysis to detail the global program of gene expression underlying changes in mDC function during HIV infection.
Project description:Abstract Objectives: HIV infection dysregulates the innate immune system and alters leukocyte gene expression. The objectives were two fold: to characterize the impact of HIV infection on peripheral monocyte gene expression and to identify the predominant factor(s) responsible for altered gene expression. Design and methods: In a cross-sectional study, CD14+ monocytes were isolated from 11 HIV seronegative controls, 22 HIV seropositive subjects with low viral loads (LVL, <= 10,000 RNA copies/ml) and 22 HIV seropositive subjects with high viral loads (HVL, > 10,000 RNA/copies/ml). Total monocyte RNA was hybridized to 55K probes on high-density microarrays to obtained detailed gene expression profiles from control, LVL and HVL subjects. As potential candidates for immune disruption, we evaluated three HIV-related peripheral factors, interferon (IFN)-a, IFN-a and lipopolysaccharide (LPS) by treating HIV seronegative CD14+ monocytes for 48h and then analyzing gene expression. Plasma collected from the HIV subjects were quantified for LPS using a Pyrogene assay and for soluble (s) CD14 by ELISA. Results: In this cross-sectional study of HIV subjects (n=44), viral loads above 10,000 RNA copies/ml were associated with an activated phenotype. Characterization of the gene expression pattern by Gene Ontology reveals an ongoing immune response to viral infection including inflammation and chemotaxis. Gene expression analysis of in vitro treated HIV seronegative monocytes with IFN-a, IFN-g or LPS demonstrated that IFN-a most accurately recapitulated the HIV HVL profile. There was no detectable LPS signature even in those HIV subjects with the highest LPS and sCD14 levels. Conclusions: Monocyte gene expression in subjects with viremia is predominantly due to IFN-a, while subjects with LVL have a non-activated phenotype. In monocytes, there was no discernible expression profile linked to LPS exposure.
Project description:CD11c+ Myeloid Dendritic Cells (mDCs) were isolated from the peripheral blood mononuclear cells (PBMCs) of HIV uninfected and HIV infected subjects. The expression of CD11c+ mDCs was accessed to determine how HIV infection may play a role on the expression profiles of these cells. mDCs are known to play a role in antigen presentation, and thus are pivotal in immune sensing and priming of the adaptive immune response. We wanted to see if the change in immune system function during chronic HIV infection may be due to defects in this cell subtype. We used microarray analysis to detail the global program of gene expression underlying changes in mDC function during HIV infection. PBMCs were isolated from HIV uninfected and HIV infected blood samples. CD11c+ cells were sorted from the whole PBMC population by magnetic bead sorting (anti-CD11c antibody bound to a magnetic bead inclubated with whole PBMCs). RNA was isolated from this sorted population to get the gene expression of this subtype of cells.