A5078727888- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cytomegalovirus and herpesvirus research
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- Peroxisome Proliferator-Activated Receptors
- Angiogenesis and VEGF in Cancer
- Protein Degradation and Inhibitors
- Congenital heart defects research
- RNA modifications and cancer
- Herpesvirus Infections and Treatments
- Animal Disease Management and Epidemiology
- Carbohydrate Chemistry and Synthesis
- Cholesterol and Lipid Metabolism
- Bacteriophages and microbial interactions
- PI3K/AKT/mTOR signaling in cancer
- Apelin-related biomedical research
- Endoplasmic Reticulum Stress and Disease
- Protein Structure and Dynamics
- T-cell and Retrovirus Studies
Innsbruck Medical University
2014-2025
Universität Innsbruck
2016-2025
Université de Strasbourg
2015-2023
Centre National de la Recherche Scientifique
2015-2023
Architecture et Réactivité de l'arN
2015-2023
Institut de Biologie Moléculaire et Cellulaire
2013-2021
Centre de Recherches sur les Macromolécules Végétales
2021
Institut de Génétique Moléculaire de Montpellier
2013
National Institutes of Health
2002-2008
Frederick National Laboratory for Cancer Research
2002-2008
ABSTRACT Nucleocapsid protein (NCp7) of human immunodeficiency virus type 1 is found covering the genomic RNA in interior viral particle. It a highly basic with two zinc fingers form CX2CX4HX4C which exhibit strong affinity for cation. To study structure-function relationship N-terminal finger NCp7, this domain was either deleted or changed to CX2CX4 C X4C. We examined formation and structure as well proviral DNA synthesis. Our data show that these NC mutations result particles an abnormal...
Abstract Aims Imbalances of iron metabolism have been linked to the development atherosclerosis. However, subjects with hereditary haemochromatosis a lower prevalence cardiovascular disease. The aim our study was understand underlying mechanisms by combining data from genome-wide association analyses in humans, CRISPR/Cas9 genome editing, and loss-of-function studies mice. Methods results Our analysis Global Lipids Genetics Consortium (GLGC) dataset revealed that single nucleotide...
Abstract Aims Cardiac shockwave therapy (SWT) improves left ventricular (LV) function in patients with ischaemic cardiomyopathy. Shockwave activates Toll-like receptor 3 (TLR3), a receptor-inducing chromatin remodelling and nuclear reprogramming of cardiac cells. We hypothesized that mechanical activation TLR3 facilitates fibroblasts towards endothelial cells restoring myocardial perfusion function. Methods results Human were treated by stimulation via SWT or agonist Poly(I:C) the presence...
Recent crystallographic data suggest that conserved residues in the connection subdomain and C-terminal ribonuclease H (RNase H) domain of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) contact nascent DNA primer modulate trajectory template relative to RNase catalytic center. Within domain, these include Thr473, Glu475, Lys476, Tyr501, Ile505, while His539 Asn474 interact with scissile phosphate RNA template. Amino acid substitutions at several positions were evaluated...
Recent evidence indicates that the HIV-1 Integrase (IN) binds viral genomic RNA (gRNA), playing a critical role in morphogenesis of particle and stability gRNA once host cell. By combining biophysical, molecular biology, biochemical approaches, we found 18-residues flexible C-terminal tail IN acts as sensor peculiar apical structure trans-activation response element (TAR), interacting with its hexaloop. We show binding whole domain modifies TAR structure, exposing nucleotides. These...
The reverse transcriptase-associated ribonuclease H (RT/RNase H) domains from the gypsy group of retrotransposons, which Ty3 is a member, share considerable sequence homology with their retroviral counterparts. However, thegypsy elements have conserved tyrosine (position 459 in RT) instead histidine catalytic center RTs such as at position 539 HIV-1. In addition, shows conservation adjacent to third metal-chelating carboxylate residues, Asp-426 RT. role these and additional residues was...
Introduction . DPP4 inhibitors (gliptins) are commonly used antidiabetic drugs for the treatment of type 2 diabetes. Gliptins also act in a glucose-independent manner and show vasoregenerative effects. We have shown that gliptins can remarkably accelerate vascular healing after injury. However, underlying mechanisms remain unclear. Here, we examined potential signaling pathways linking to enhanced endothelial regeneration. Methods Results wild-type GLP1 receptor knockout ( Glp1r −/− ) mice...
To probe structural features of a polypurine tract (PPT) that mediate its specific recognition and processing, model 20 bp RNA/DNA hybrid duplex, which includes the full PPT sequence Saccharomyces cerevisiae LTR-retrotransposon Ty3, has been investigated using solution NMR spectroscopy. While homonuclear NOESY DQF-COSY analyses indicate this PPT-containing adopts an overall A-form-like helical geometry, unexpected sugar pucker switch detected for ribose at position +1, relative to cleavage...
Amino acid sequence alignment was used to identify the putative thumb subdomain of reverse transcriptase (RT) from Saccharomyces cerevisiae long terminal repeat-containing retrotransposon Ty3. The counterpart helix alphaH human immunodeficiency virus type 1 (HIV-1) RT, which mediates important interactions with a duplex nucleic approximately 3-6 bp behind DNA polymerase catalytic center, identified between amino acids 290 and 298 Ty3 enzyme. consequences substituting RT Gln290, Phe292,...
Intensive studies of HIV-1 have revealed its extraordinary ability to adapt environmental and immunological challenges, an that is also at the basis antiviral treatment escape. Here, by deconvoluting different roles viral integrase in various steps infectious cycle, we report how existence alternative equally efficient structural arrangements for carrying out one function opens up possibility adapting optimization further functionalities exerted same protein. Such a property provides asset...
It has been shown that peptide libraries are powerful tools for the identification of peptides showing new binding specificity. This technology was applied to isolation HIV-1 nucleocapsid protein (NCp7). Three different prolin reach sequences, interacting with NCp7, were isolated, from a constrained phage displayed-peptide library 10(8) independent clones. The three isolated library, bind NCp7 in region 30-52. Moreover, two them share PP-(D/E)R consensus sequence.
ABSTRACT Recent evidence indicated that HIV-1 Integrase (IN) binds genomic viral RNA (gRNA) playing a critical role in particle morphogenesis and gRNA stability host cells. Combining biophysical biochemical approaches we show the C-terminal flexible 18-residues tail of IN acts as sensor peculiar apical structure trans-activation response element (TAR), directly interacting with its hexaloop. We highlighted how whole domain, once bound to TAR, can change assisting binding Tat, HIV...
Identifying enzymes that, once introduced in cancer cells, lead to an increased efficiency of treatment constitutes important goal for biomedical applications. Using original procedure whereby mutant genes are generated based on the use conditional lentivector genome mobilisation, we recently described, first time, identification a human deoxycytidine kinase (dCK) (G12) that sensitises panel cell lines with dCK analogue gemcitabine. Here, starting from G12 variant itself, new library and...
Transmissions of simian viruses to humans has originated the different groups HIV-1. We recently identified a functional motif (CLA), in C-terminal domain integrase, essential for integration HIV-1 group M. Here, we found that is instead dispensable O isolates, because presence, N-terminal specific sequence, Q7G27P41H44, define as NOG motif. Alterations reverse transcription and 3' processing observed by mutating CLA IN M are fully rescued wt levels inserting sequence N-ter protein. These...
Generating chimerical integrases between isolates of the HIV-1 group responsible for AIDS pandemic (group M) and minor O, we identify a new functional motif, in C-terminal domain M, constituted two lysines asparagines (NKNK). Removing these residues abolishes catalysis vitro generation proviral DNA tissue culture. A decrease reverse transcription nuclear import products is also observed. Remarkably, motif shows potential genetic flexibility with respect to integration. Indeed, despite its...