A5049338002- HIV Research and Treatment
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Salivary Gland Disorders and Functions
- Caveolin-1 and cellular processes
- HIV/AIDS drug development and treatment
- CAR-T cell therapy research
- Advanced Fluorescence Microscopy Techniques
- COVID-19 Clinical Research Studies
- Cell Adhesion Molecules Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- Chronic Myeloid Leukemia Treatments
- Advanced Biosensing Techniques and Applications
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Cell Image Analysis Techniques
University Hospital Heidelberg
2011-2023
Heidelberg University
2011-2023
University of Bern
2012-2020
National Center for Infectious Diseases
2018
Abstract The overall composition of the mammalian intestinal microbiota varies between individuals: within each individual there are differences along length tract related to host nutrition, motility and secretions. Mucus is a highly regenerative protective lubricant glycoprotein sheet secreted by goblet cells; inner mucus layer nearly sterile. Here we show that outer large intestine forms unique microbial niche with distinct communities, including bacteria without specialized mucolytic...
SARS-CoV-2 variants of concern (VOCs) display enhanced transmissibility and resistance to antibody neutralization. Comparing the early 2020 isolate EU-1 VOCs Alpha, Beta, Gamma in mice transgenic for human ACE2 reveals that induce a broadened scope symptoms, expand systemic infection gastrointestinal tract, elicit depletion natural killer cells, trigger variant-specific cytokine production patterns. infections result accelerated disease progression associated with increased immune activation...
ABSTRACT HIV-1 Nef and Vpu are thought to optimize virus replication in the infected host, at least part via their ability interfere with vesicular host cell trafficking. Despite use of distinct molecular mechanisms, share specificity for some molecules such as CD4 major histocompatibility complex class I (MHC-I), while disruption intracellular transport restriction factor CD317/tetherin represents a specialized activity not exerted by Nef. To establish profile receptors whose is affected...
This study defines calcium-dependent actin polymerization by nuclear Arp2/3 complex as essential for CD4 + T cell help.
Salivary gland memory CD8 + T cells use distinct motility modes and cooperate with tissue macrophages for organ surveillance.
The lack of effective antiviral treatments against SARS-CoV-2 is a significant limitation in the fight COVID-19 pandemic. Single-drug regimens have so far yielded limited results, indicating that combinations antivirals might be required, as previously seen for other RNA viruses.
HIV-1 negative factor (Nef) elevates virus replication and contributes to immune evasion in vivo. As one of its established vitro activities, Nef interferes with T-lymphocyte chemotaxis by reducing host cell actin dynamics. To explore Nef’s influence on vivo recirculation T lymphocytes, we assessed lymph-node homing Nef-expressing primary murine lymphocytes found a drastic impairment peripheral lymph nodes. Intravital imaging 3D immunofluorescence reconstruction nodes revealed that potently...
SERINC3 (serine incorporator 3) and SERINC5 are recently identified host cell inhibitors of HIV-1 particle infectivity that counteracted by the viral pathogenesis factor Nef. Here we confirm Nef, but not Vpu, antagonizes restriction SERINC5. antagonism occurred in parallel with other Nef activities, including surface receptor downregulation, trans-Golgi network targeting Lck, inhibition actin dynamics. Interaction motifs endocytic machinery Nef-associated kinase complex, as well CD4...
<title>Abstract</title> Sensing of viral pathogens by RIG-I-like receptors (RLRs) requires their priming via dephosphorylation mediated the protein phosphatase 1 regulatory subunit 12C (R12C), which is activated upon virus-induced actin rearrangements. Here, we show that HIV-1 accessory Nef disrupts R12C-mediated RLR priming, thereby preventing efficient sensing. variants containing single point mutations in (F/R191A) ablate its ability to bind actin-modulating kinase PAK2 trigger increased...
Despite rapid development and deployment of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant modalities to curb the pandemic by directly attacking virus on a genetic level remain highly desirable are urgently needed. Here we comprehensively illustrate capacity adeno-associated (AAV) vectors co-expressing cocktail three short hairpin RNAs (shRNAs; RNAi triggers) directed SARS-CoV-2 RdRp N genes as versatile effective antiviral agents. In...
Nef is an accessory protein and pathogenicity factor of human immunodeficiency virus (HIV) simian (SIV) which elevates replication in vivo. We recently described for HIV type 1(SF2) (HIV-1(SF2)) the potent interference with T-lymphocyte chemotaxis via its association cellular kinase PAK2. Mechanistic analysis revealed that this interaction results deregulation actin-severing cofilin thus blocks chemokine-mediated actin remodeling required cell motility. However, efficiency PAK2 highly...
T cells are actively scanning pMHC-presenting in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies confinement. How the cell actomyosin cytoskeleton facilitates this task distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator small GTPase Rho, led to increased Rho-GTP levels surface stiffness primary cells. Nonetheless, intravital imaging revealed robust motility Myo9b-/- CD8+ tissue similar expansion...
Article4 November 2020Open Access Source DataTransparent process HIV-1 infection of CD4 T cells impairs antigen-specific B cell function Sheetal Kaw Department Infectious Diseases, Integrative Virology, University Hospital Heidelberg, Germany Search for more papers by this author Swetha Ananth German Centre Infection Research (DZIF), Partner Site Nikolaos Tsopoulidis Katharina Morath Bahar M Coban Ralph Hohenberger Otorhinolaryngology, Olcay C Bulut Head and Neck Surgery, SLK Klinikum Am...
HIV-1 Nef critically determines virus spread and disease progression in infected individuals by acting as a protein interaction adaptor via incompletely defined mechanisms ligands. Residues 12 to 39 near the N terminus of have been described an platform for Nef-associated kinase complex (NAKC) were recently identified essential determinants broad range activities. Here, we report systematic mapping this amino acid stretch that revealed presence three independent motifs with specific ligands...
Flotillin-1 (Flot1) is an evolutionary conserved, ubiquitously expressed lipid raft-associated scaffolding protein. Migration of Flot1-deficient neutrophils impaired because a decrease in myosin II-mediated contractility. Flot1 also accumulates the uropod polarized T cells, suggesting analogous role cell migration. In this study, we analyzed morphology and migration parameters murine wild-type Flot1-/- CD8+ cells using vitro assays intravital two-photon microscopy lymphoid nonlymphoid...
Abstract Background The Nef protein of HIV facilitates virus replication and disease progression in infected patients. This role as pathogenesis factor depends on several genetically separable functions that are mediated by interactions highly conserved protein-protein interaction motifs with different host cell proteins. By studying the functionality a series nef alleles from clinical isolates, we identified dysfunctional group O which valine-glycine-phenylalanine (VGF) region, links...
Abstract Immature dendritic cells (iDCs) migrate in microenvironments with distinct cell and extracellular matrix densities vivo contribute to HIV‐1 dissemination mounting of antiviral immune responses. Here, we find that, compared standard 2D suspension cultures, 3D collagen as tissue‐like environment alters iDC properties their response infection. iDCs adopt an elongated morphology increased deformability at unaltered activation, differentiation, cytokine secretion, or responsiveness LPS....
Tissue-resident CD8+ T cells (TRM) continuously scan peptide-MHC (pMHC) complexes in their organ of residence to intercept microbial invaders. Recent data showed that TRM lodged exocrine glands tissue the absence any chemoattractant or adhesion receptor signaling, thus bypassing requirement for canonical migration-promoting factors. The signals eliciting this noncanonical motility and its relevance surveillance have remained unknown. Using mouse models viral infections, we report gland...
Abstract HIV-1 Nef is a multifunctional protein that optimizes virus spread and promotes immune evasion of infected cells to accelerate disease progression in AIDS patients. As one its activities, reduces the motility CD4+ T lymphocytes confined space. In vivo, restricts lymphocyte homing lymph nodes as it ability for extravasation at diapedesis step. Effects on are typically mediated by reduce actin remodeling. However, interference with does not depend residues required inhibition host...
The submandibular salivary gland (SMG) is one of the three major glands, and interest for many different fields biological research, including cell biology, oncology, dentistry, immunology. SMG an exocrine comprised secretory epithelial cells, myofibroblasts, endothelial nerves, extracellular matrix. Dynamic cellular processes in rat mouse have previously been imaged, mostly using inverted multi-photon microscope systems. Here, we describe a straightforward protocol surgical preparation...