A5045754024- HIV Research and Treatment
- interferon and immune responses
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- Herpesvirus Infections and Treatments
- RNA Research and Splicing
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Animal Virus Infections Studies
- Hepatitis B Virus Studies
- Advanced biosensing and bioanalysis techniques
- Influenza Virus Research Studies
- Pluripotent Stem Cells Research
- Cancer Immunotherapy and Biomarkers
- Systemic Lupus Erythematosus Research
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
Paul Ehrlich Institut
2015-2024
Discovery Institute
2015-2020
Sanford Burnham Prebys Medical Discovery Institute
2009-2020
German Center for Infection Research
2015-2020
Goethe University Frankfurt
1995-2014
Genomics Institute of the Novartis Research Foundation
2007
Salk Institute for Biological Studies
2003-2005
Johannes Gutenberg University Mainz
1990
University of Göttingen
1984
Myeloid blood cells are largely resistant to infection with human immunodeficiency virus type 1 (HIV-1). Recently, it was reported that Vpx from HIV-2/SIVsm facilitates of these by counteracting the host restriction factor SAMHD1. Here, we independently confirmed interacts SAMHD1 and targets for ubiquitin-mediated degradation. We found Vpx-mediated degradation rendered primary monocytes highly susceptible HIV-1 infection; a T17A mutation, defective binding degradation, did not show this...
In the human genome apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC)3 gene has expanded into a tandem array of genes termed APOBEC3A-G. Two members this family, APOBEC3G and APOBEC3F, have been found to potent activity against virion infectivity factor deficient (Deltavif) immunodeficiency virus 1 (HIV-1). These enzymes become encapsidated in Deltavif HIV-1 virions next round infection deaminate newly synthesized reverse transcripts. The lentiviral Vif protein prevents...
Genome-wide siRNA screens have identified host cell factors important for efficient HIV infection, among which are nuclear pore proteins such as RanBP2/Nup358 and the karyopherin Transportin-3/TNPO3. Analysis of roles these in replication cycle suggested that correct trafficking through may facilitate subsequent integration step. Here we present data coupling between steps by demonstrating depletion Transportin-3 or RanBP2 altered terminal step early replication, selection chromosomal sites...
The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as the causative agent of a severe disease with fatality rate approximately 30%. high virulence and mortality prompted us to analyze aspects MERS-CoV pathogenesis, especially its interaction innate immune cells such antigen-presenting (APCs). Particularly, we analyzed secretion type I III interferons (IFNs) by APCs, i.e., B cells, macrophages, monocyte-derived/myeloid dendritic (MDDCs/mDCs), plasmacytoid (pDCs) human...
Sensing of human immunodeficiency virus type 1 (HIV-1) DNA is mediated by the cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) signaling axis. Signal transduction and regulation this cascade achieved post-translational modifications. Here we show that cGAS-STING-dependent HIV-1 sensing requires interferon-stimulated gene 15 (ISG15). ISG15 deficiency inhibits STING-dependent STING agonist-induced antiviral response. Upon external stimuli, undergoes ISGylation at residues K224,...
Abstract Deoxynucleotide triphosphates (dNTPs) are essential for efficient hepatitis B virus (HBV) replication. Here, we investigated the influence of restriction factor SAMHD1, a dNTP hydrolase (dNTPase) and RNase, on HBV We demonstrated that silencing SAMHD1 in hepatic cells increased replication, while overexpression had opposite effect. significantly affected levels extracellular viral DNA as well intracellular reverse transcription products, without affecting RNAs or cccDNA. mutations...
Abstract SAMHD1 is a critical restriction factor for HIV-1 in non-cycling cells and its antiviral activity regulated by T592 phosphorylation. Here, we show that dephosphorylation at controlled during the cell cycle, occurring M/G 1 transition proliferating cells. Using several complementary proteomics biochemical approaches, identify phosphatase PP2A-B55α responsible rendering antivirally active. specifically targeted holoenzymes mitotic exit, line with observations key exit mammalian...
Significance HIV infection can be restricted by different host cell proteins. One such restriction factor is SAM domain and HD domain-containing protein 1 (SAMHD1), a triphosphohydrolase that cleaves dNTPs, which are required for reverse transcription. The accessory lentiviral X (Vpx) from simian immunodeficiency viruses (SIV) of sooty mangabeys rhesus macaques or HIV-2 degrade SAMHD1. Here we show Vpx proteins SIVs red-capped mandrills enhance resting CD4 T cells, but not macrophages,...
Hepatitis B virus (HBV) chronic infection is a critical risk factor for hepatocellular carcinoma. The innate immune response to HBV matter of debate. In particular, viral escape mechanisms are poorly understood. Our study reveals that RNAs not immunostimulatory in immunocompetent myeloid cells. contrast, DNA from particles and replication intermediates sensed by cyclic GMP-AMP Synthase (cGAS) Stimulator Interferon Genes (STING). We show primary human hepatocytes express sensors reduced...
Large polyglutamine expansions in Ataxin-2 (ATXN2) cause multi-system nervous atrophy Spinocerebellar Ataxia type 2 (SCA2). Intermediate size carry a risk for selective motor neuron degeneration, known as Amyotrophic Lateral Sclerosis (ALS). Conversely, the depletion of ATXN2 prevents disease progression ALS. Although interacts directly with RNA, and ALS pathogenesis there is crucial role RNA toxicity, affected functional pathways remain ill defined. Here, we examined an authentic SCA2 mouse...