A5021055466- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- interferon and immune responses
- Hepatitis C virus research
- Biochemical and Molecular Research
- Chemical Reactions and Isotopes
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- T-cell and Retrovirus Studies
- Hormonal Regulation and Hypertension
- Hepatitis B Virus Studies
- Liver Disease Diagnosis and Treatment
- Receptor Mechanisms and Signaling
- Animal Disease Management and Epidemiology
- Mosquito-borne diseases and control
Paul Ehrlich Institut
2016-2024
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...
Macrophages and dendritic cells are usually the first point of contact with pathogens, including lentiviruses. Host restriction factors, SAMHD1, mediate innate immune response against these viruses. However, HIV-1 has evolved to circumvent establishes disseminated infection. The cyclin-dependent kinase inhibitor p21, which is involved in differentiation maturation monocytes, blocks replication at reverse transcription step. p21 thought suppress key enzymes dNTP biosynthesis activates SAMHD1...
We introduce BLaER1 cells as an alternative myeloid cell model in combination with CRISPR/Cas9-mediated gene editing to study the influence of sterile α motif and HD domain-containing protein 1 (SAMHD1) T592 phosphorylation on anti-viral restriction control cellular dNTP levels endogenous, physiologically relevant context. A proper understanding mechanism function SAMHD1 will provide attractive strategies aiming at selectively manipulating without affecting other functions. Even more, our...
ABSTRACT In humans, sterile alpha motif (SAM) domain- and histidine–aspartic acid (HD) domain-containing protein 1 (SAMHD1) is a dNTPase enzyme that prevents HIV-1 infection in non-cycling cells, such as differentiated THP-1 cells human primary macrophages. Although phosphorylation of threonine 592 (T592) SAMHD1 recognized the regulator ability to prevent infection, contributions acetylation this remain unknown. Mass spectrometry analysis proteins derived from cycling B macrophages revealed...
Abstract Sterile α motif (SAM) and HD domain-containing protein 1 (SAMHD1) is a potent restriction factor for immunodeficiency virus (HIV-1), active in myeloid resting CD4 + T cells. As dNTP triphosphate triphosphohydrolase (dNTPase), SAMHD1 proposed to limit cellular levels correlating with inhibition of HIV-1 reverse transcription. The anti-viral activity regulated by dephosphorylation the residue T592. However, impact T592 phosphorylation on dNTPase still under debate. Whether additional...
Sterile α motif (SAM) and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphate triphosphohydrolase (dNTPase) potent restriction factor for immunodeficiency virus (HIV-1), active in myeloid resting CD4+ T cells. The anti-viral activity of SAMHD1 regulated by dephosphorylation the residue T592. However, impact T592 phosphorylation on dNTPase still under debate. Whether additional cellular functions not completely understood. We report BLaER1 cells as novel human macrophage HIV-1...