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:HIV infection produces a chronic inflammation which leads to early aging of people living with HIV. Even though antiretroviral treatments (ART) have significantly increased HIV patient survival, an underlying chronic inflammation persists leading to HIV-related comorbidities. In this context, changes in microRNAs (miRNAs) expression may contribute to this inflammatory response. This study aims to detect differential expression of circulating miRNAs in treatment-naïve HIV individuals compared to uninfected controls and evaluation of altered miRNAs after one year of ART. Serum miRNAs from patients and controls were analysed using next generation sequencing.
Project description:Chronic liver disease is becoming a leading cause of illness and mortality in people living with human immunodeficiency virus (HIV) (PLWH) undergoing suppressive anti-retroviral therapy. Its main etiology has been reported to be coinfection with hepatitis B (HBV) and C (HCV) viruses. Accumulating evidence indicate chronic liver inflammation and fibrosis can potentially lead to the development of hepatocellular carcinoma (HCC). Therefore, monitoring of the disease progression in PLWH is required. The present study aimed to explore the plasma protein profiles of patients with HIV infection and those coinfected with HBV and HCV using shotgun proteomics.
Project description:Throughout HIV-1 replication cycle, a complex interplay of host-pathogen interactions takes place in the infected cell, leading to production of new virions. The virus modulates the host cellular machinery in order to support its life cycle, while controlling intracellular defense. We have investigated the dynamic host response to HIV-1 infection by systematically measuring transcriptome, proteome and phosphoproteome expression changes in infected and uninfected SupT1 CD4+ T cells at 5 time-points throughout the HIV-1 replication cycle. Genome-wide transcript levels were assessed by RNA-Seq, while protein and phosphoprotein relative abundances were obtained using SILAC mass spectrometry. By the means of a Gaussian mixed-effects model, we stratified host genes based on their gene expression temporal patterns at the three levels, showing how HIV may affect regulation of certain host genes. The results of the implemented integrative analysis of time-series omics data offers a catalogue of dynamic host response to HIV infection allowing a more comprehensive understanding of host-virus interactions. Furthermore, it facilitates identifying novel host factors potentially promoting or restricting HIV replication.
Project description:Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short FG peptides to isolated capsid hexamers have been characterized, how these proteins engage biologically relevant extended HIV-1 capsid lattices is unknown. We have identified that prion-like low complexity regions (LCR) enable avid binding of CPSF6, NUP153 and SEC24C to curved hexameric capsid lattices. Structural studies reveal that LCR-LCR interactions mediate multivalent CPSF6 assembly, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. CPSF6 LCR mediated avid binding to HIV-1 cores is essential for functional virus-host interactions in infected cells. Investigational drug lenacapavir can access unoccupied hydrophobic pockets in the CPSF6-HIV-1 complex and potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results elucidate previously undescribed mechanisms of virus-host interactions and potent inhibition of HIV-1.
Project description:This SuperSeries is composed of the following subset Series: GSE24037: Salivary cytokine alterations in HIV infection part 1 GSE24064: Salivary cytokine alterations in HIV infection part 2 Refer to individual Series
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: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.
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.