A5080716335- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Computational Drug Discovery Methods
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- interferon and immune responses
- Microbial Natural Products and Biosynthesis
- Immune Response and Inflammation
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Advanced biosensing and bioanalysis techniques
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Immune cells in cancer
- Alzheimer's disease research and treatments
- Metabolomics and Mass Spectrometry Studies
- Immunodeficiency and Autoimmune Disorders
- COVID-19 Clinical Research Studies
- Bioinformatics and Genomic Networks
- Synthesis and biological activity
- Blood groups and transfusion
- Mosquito-borne diseases and control
- Cholinesterase and Neurodegenerative Diseases
Universitat Politècnica de Catalunya
2017-2021
Institute for Research in Biomedicine
2017-2021
Universitat Autònoma de Barcelona
2006-2017
IrsiCaixa
2007-2017
Hospital Universitari Germans Trias i Pujol
2005-2015
University of Dundee
2012-2014
MRC Protein Phosphorylation and Ubiquitylation Unit
2013-2014
Medical Research Council
2013
Abstract Proliferating cells are preferentially susceptible to infection by retroviruses. Sterile α motif and HD domain–containing protein-1 (SAMHD1) is a recently described deoxynucleotide phosphohydrolase controlling the size of intracellular triphosphate (dNTP) pool, limiting factor for retroviral reverse transcription in noncycling cells. (Ki67+) primary CD4+ T or macrophages express phosphorylated form SAMHD1 that corresponds with susceptibility cell culture. We identified...
Abstract Chemical descriptors encode the physicochemical and structural properties of small molecules, they are at core chemoinformatics. The broad release bioactivity data has prompted enriched representations compounds, reaching beyond chemical structures capturing their known biological properties. Unfortunately, not available for most which limits applicability to a few thousand well characterized compounds. Here we present collection deep neural networks able infer signatures any...
The roles of IL-1R-associated kinase (IRAK)2 and IRAK1 in cytokine production were investigated using immune cells from knock-in mice expressing the TNFR-associated factor 6 (TRAF6) binding-defective mutant IRAK2[E525A] or catalytically inactive IRAK1[D359A] mutant. In bone marrow-derived macrophages (BMDMs), IRAK2-TRAF6 interaction was required for late (2-8 h) but not early phase (0-2 il6 tnfa mRNA production, hence IL-6 TNF-α secretion by TLR agonists that signal via MyD88. Loss had...
We developed a pharmacophore model for type II inhibitors that was used to guide the construction of library kinase inhibitors. Kinome-wide selectivity profiling resulted in identification series 4-substituted 1H-pyrrolo[2,3-b]pyridines exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well pharmacologically interrogated such p38α (MAPK14) ABL. Further investigation structure-activity relationship (SAR) dual MAP4K2 1...
Monocyte-derived macrophages (MDM) can polarize into different subsets depending on the environment and activation signal to which they are submitted. Differentiation allows HIV-1 strains infect cells of monocytic lineage. In this study, we show that culture monocytes with a combination IL-12 IL-18 led macrophage differentiation was resistant infection. contrast, M-CSF-derived MDM were readily infected by HIV-1. When differentiated in presence M-CSF then further treated IL-12/IL-18, became...
Background: Sterile α motif and HD domain-containing protein-1 (SAMHD1) inhibits HIV-1 reverse transcription by decreasing the pool of intracellular deoxynucleotides. SAMHD1 is controlled cyclin-dependent kinase (CDK)-mediated phosphorylation. However, exact mechanism regulation in primary cells unclear. We explore effect palbociclib, a CDK6 inhibitor, replication. Methods: Human monocytes were differentiated into macrophages with monocyte-colony stimulating factor CD4+ T lymphocytes...
ObjectivesSterile α motif and histidine–aspartate domain-containing protein 1 (SAMHD1) has been shown to restrict retroviruses DNA viruses by decreasing the pool of intracellular deoxynucleotides. In turn, SAMHD1 is controlled cyclin-dependent kinases (CDK) that regulate cell cycle proliferation. Here, we explore effect CDK6 inhibitors on replication herpes simplex virus type (HSV-1) in primary monocyte-derived macrophages (MDM).
Cyclins control the activation of cyclin-dependent kinases (CDK), which in turn, cell cycle and division. Intracellular availability deoxynucleotides (dNTP) plays a fundamental role progression. SAM domain HD domain-containing protein 1 (SAMHD1) degrades nucleotide triphosphates controls size dNTP pool. SAMHD1 activity appears to be controlled by CDK. Here, we show that knockdown cyclin D3 partner CDK6 E2 CDK2 had major impact phosphorylation inactivation led decreased levels inhibition...
Background: HIV-1 coreceptor switch from CCR5 to CXCR4 is associated with disease progression and AIDS. Selection of resistant agents in cell culture has often occurred the absence switch. With antagonists currently clinical trials, their impact on use still doubt. Methods: Six R5 strains were passaged lymphoid cells expressing high low CCR5, or presence inhibitors (TAK-779, mAb 2D7 CCL5). AMD3100, zidovudine lamivudine used as controls. Phenotype genotype changes well virus evaluated....
We have studied the mechanism of action Arg<sup>*</sup>-Arg-Nal<sup>2</sup>-Cys(1×)-Tyr-Gln-Lys-(d-Pro)-Pro-Tyr-Arg-Cit-Cys(1×)-Arg-Gly-(d-Pro)<sup>*</sup> (POL3026), a novel specific β-hairpin mimetic CXC chemokine receptor (CXCR)4 antagonist. POL3026 specifically blocked binding anti-CXCR4 monoclonal antibody 12G5 and intracellular Ca<sup>2+</sup> signal induced by ligand 12. consistently replication human immunodeficiency virus (HIV), including wide panel X4 dualtropic strains subtypes in...
BackgroundHuman immunodeficiency virus (HIV) takes advantage of multiple host proteins to support its own replication. The gene ZNRD1 (zinc ribbon domain-containing 1) has been identified as encoding a potential factor that influenced disease progression in HIV-positive individuals genomewide association study and also significantly affected HIV replication large-scale vitro short interfering RNA (siRNA) screen. Genes polymorphisms by analysis need be followed up means functional assays...
Plasmacytoid dendritic cells (pDCs) are characterized by their ability to produce high levels of type 1 interferons in response ligands that activate TLR7 and TLR9, but the signaling pathways required for IFN production incompletely understood. Here we exploit human pDC cell line Gen2.2 improved pharmacological inhibitors protein kinases address this issue. We demonstrate TLR9 require TAK1-IKKβ pathway induce IFNβ via a is independent degradation IκBα. also show IKKβ activity, as well...
ABSTRACT Sterile alpha motif and histidine-aspartic domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase recently recognized as an antiviral factor that acts by depleting dNTP availability for viral reverse transcriptase (RT). SAMHD1 restriction counteracted the human immunodeficiency virus type 2 (HIV-2) accessory Vpx, which targets proteosomal degradation, resulting in increased of dNTPs consequently enhanced replication. Nucleoside inhibitors...
SAMHD1 and the CDKN1A (p21) cyclin-dependent kinase inhibitor have been postulated to mediate HIV-1 restriction in CD4+ cells. We shown that p21 affects HIV replication through its effect on SAMHD1. Thus, we aimed at evaluating expression of different HIV+ phenotypic groups. evaluated mRNA T cells from individuals including elite controllers (n = 12), who control without need for antiretroviral treatment, viraemic progressors 10) seronegative healthy donors 14). Immunological variables were...
Abstract Monocytes and macrophages are targets of HIV-1 infection play critical roles in multiple aspects viral pathogenesis. During the differentiation monocytes to macrophages, adhesion molecules such as integrins upregulated; therefore, they provide signals that control process subsequently may render more susceptible infection. Previous work demonstrated blocking αv-containing triggered a signal transduction pathway leading inhibition NF-κB–dependent transcription. In this paper, we show...
Abstract Background In spite of many years research, our understanding the molecular bases Alzheimer’s disease (AD) is still incomplete, and medical treatments available mainly target symptoms are hardly effective. Indeed, modulation a single (e.g., β-secretase) has proven to be insufficient significantly alter physiopathology disease, we should therefore move from gene-centric systemic therapeutic strategies, where AD-related changes modulated globally. Methods Here present complete...
Abstract p53 expression and activation have been associated to faster human immunodeficiency virus (HIV) disease progression, most probably by inducing CD4+ T cell death but also through its cooperative effect in the control of viral gene transcription regulatory proteins. Here, we show that RNA interference HIV-1 reporter (HeLa P4-R5 MAGI) lymphoid (SupT1) lines blocked Tat-induced from promoter replication acutely infected cells, suggesting a role transcription. Contrary SupT1 which encoe...