keyword
MENU ▼
Read by QxMD icon Read
search

SAMHD1

keyword
https://www.readbyqxmd.com/read/28321930/uncovering-allostery-and-regulation-in-samhd1-through-molecular-dynamics-simulations
#1
Kajwal Kumar Patra, Akash Bhattacharya, Swati Bhattacharya
The human sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a retroviral restriction factor in myeloid cells and non-cycling CD4+ T cells, a feature imputed to its phosphohydrolase activity - the enzyme depletes the cellular dNTP levels inhibiting reverse transcription. The functionally active form of SAMHD1 is an allosterically triggered tetramer which utilizes GTP-Mg(+2) -dNTP cross bridges to link and stabilize adjacent monomers. However, very little is known about how it assembles into a tetramer and how long the tetramer stays intact...
March 21, 2017: Proteins
https://www.readbyqxmd.com/read/28289923/tocilizumab-reverses-cerebral-vasculopathy-in-a-patient-with-homozygous-samhd1-mutation
#2
REVIEW
Michael Henrickson, Heng Wang
An auto-inflammatory syndrome consequent to SAMHD1 mutations involves cerebral vasculopathy characterized by multifocal stenosis and aneurysms within large arteries, moyamoya, chronic ischemia, and early-onset strokes (SAMS). While this condition involves the innate immune system, additional clinical features mimic systemic lupus erythematosus. Mutations in this gene can also cause a subset of the rare genetic condition Aicardi-Goutières syndrome. To date, no established therapy successfully prevents disease progression...
March 13, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28284276/zinc-binding-site-of-human-immunodeficiency-virus-2-vpx-prevents-instability-and-dysfunction-of-the-protein
#3
Minami Yamamoto, Ryoko Koga, Haruna Fujino, Kazunori Shimagaki, Halil Ibrahim Ciftci, Masahiro Kamo, Hiroshi Tateishi, Masami Otsuka, Mikako Fujita
Human immunodeficiency virus 2 Vpx coordinates zinc through residues H39, H82, C87 and C89. We reported previously that H39, H82 and C87 mutants maintain Vpx activity to facilitate the degradation of SAMHD1. Herein, the expression of Vpx mutants in cells was examined in detail. We demonstrated that the zinc-binding site stabilizes the protein to keep its function in virus growth when low levels of Vpx are expressed. At higher levels of expression, Vpx aggregation could occur, and zinc binding would suppress such aggregation...
February 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28251415/a-molecular-dynamics-simulation-study-decodes-the-early-stage-of-the-disassembly-process-abolishing-the-human-samhd1-function
#4
Francesca Cardamone, Federico Iacovelli, Giovanni Chillemi, Mattia Falconi, Alessandro Desideri
The human sterile alpha motif SAM and HD domain-containing protein 1 (SAMHD1) restricts in non-cycling cells type the infection of a large range of retroviruses including HIV-1, reducing the intracellular pool concentration of deoxynucleoside triphosphates (dNTPs) required for the reverse transcription of the viral genome. The enzyme is in equilibrium between different forms depending on bound cofactors and substrate. In this work, two SAMHD1 three-dimensional models have been investigated through classical molecular dynamics simulation, to define the role of cofactors and metal ions in the association of the tetrameric active form...
March 1, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28250118/imaging-hiv-1-genomic-dna-from-entry-through-productive-infection
#5
Ryan D Stultz, Jennifer J Cenker, David McDonald
In order to track the fate of HIV-1 particles from early entry events through productive infection, we developed a method to visualize HIV-1 DNA reverse transcription complexes by incorporation and fluorescent labeling of the thymidine analog 5-ethynyl-2' -deoxyuridine (EdU) into nascent viral DNA during cellular entry. Monocyte-derived macrophages were chosen as natural targets of HIV-1 which do not divide and therefore do not incorporate the EdU into chromosomal DNA, which would obscure detection of intranuclear HIV-1 genomes...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28229507/a-samhd1-mutation-associated-with-aicardi-gouti%C3%A3-res-syndrome-uncouples-the-ability-of-samhd1-to-restrict-hiv-1-from-its-ability-to-downmodulate-type-i-interferon-in-humans
#6
Tommy E White, Alberto Brandariz-Nuñez, Alicia Martinez-Lopez, Caitlin Knowlton, Gina Lenzi, Baek Kim, Dmitri Ivanov, Felipe Diaz-Griffero
Mutations in the human SAMHD1 gene are known to correlate with the development of the Aicardi-Goutières Syndrome (AGS), which is an inflammatory encephalopathy that exhibits neurological dysfunction characterized by increased production of type I interferon (IFN); this evidence has lead to the concept that the SAMHD1 protein negatively regulates the type I IFN response. Additionally, the SAMHD1 protein has been shown to prevent efficient HIV-1 infection of macrophages, dendritic cells and resting CD4+ T cells...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28228523/vpx-overcomes-a-samhd1-independent-block-to-hiv-reverse-transcription-that-is-specific-to-resting-cd4-t-cells
#7
Hanna-Mari Baldauf, Lena Stegmann, Sarah-Marie Schwarz, Ina Ambiel, Maud Trotard, Margarethe Martin, Manja Burggraf, Gina M Lenzi, Helena Lejk, Xiaoyu Pan, Oliver I Fregoso, Efrem S Lim, Libin Abraham, Laura A Nguyen, Frank Rutsch, Renate König, Baek Kim, Michael Emerman, Oliver T Fackler, Oliver T Keppler
Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28220857/samhd1-enhances-nucleoside-analogue-efficacy-against-hiv-1-in-myeloid-cells
#8
Paula Ordonez, Simone Kunzelmann, Harriet C T Groom, Melvyn W Yap, Simon Weising, Chris Meier, Kate N Bishop, Ian A Taylor, Jonathan P Stoye
SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcription. We now show that, in addition to this direct effect on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203649/increased-iron-export-by-ferroportin-induces-restriction-of-hiv-1-infection-in-sickle-cell-disease
#9
Namita Kumari, Tatiana Ammosova, Sharmin Diaz, Xionghao Lin, Xiaomei Niu, Andrey Ivanov, Marina Jerebtsova, Subhash Dhawan, Patricia Oneal, Sergei Nekhai
The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1)...
December 27, 2016: Blood Adv
https://www.readbyqxmd.com/read/28202763/inhibition-of-vpx-mediated-samhd1-and-vpr-mediated-hltf-degradation-by-selective-disruption-of-viral-crl4-dcaf1-e3-ubiquitin-ligase-assembly
#10
Hong Wang, Haoran Guo, Jiaming Su, Yajuan Rui, Wenwen Zheng, Wenying Gao, Wenyan Zhang, Zhaolong Li, Guanchen Liu, Wei Wei, Xiao-Fang Yu
The lentiviral accessory proteins Vpx and Vpr are known to utilize CRL4 (DCAF1) E3 ligase to induce the degradation of the host restriction factor SAMHD1 or transcriptional factor HLTF, respectively. Selective disruption of viral CRL4 (DCAF1) E3 ligase could be a promising antiviral strategy. Recently, we have determined that post-translational modification (neddylation) of Cullin-4 is required for the activation of Vpx-CRL4 (DCAF1) E3 ligase. However, the mechanism of Vpx/Vpr-CRL4 (DCAF1) E3 ligase assembly is still poorly understood...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28148784/different-expression-of-interferon-stimulated-genes-in-response-to-hiv-1-infection-in-dendritic-cells-according-to-their-maturation-state
#11
Esther Calonge, Mercedes Bermejo, Francisco Diez-Fuertes, Isabelle Mangeot, Nuria Gonzalez, Mayte Coiras, Laura Jimenez Tormo, Javier García-Perez, Nathalie Dereuddre-Bosquet, Roger Le Grand, José Alcamí
Dendritic cells (DCs) are professional antigen presenting cells whose functions are dependent on their degree of differentiation. In their immature state, DCs, capture pathogens and migrate to the lymph nodes. During this process DCs become resident mature cells specialized in antigen presentation. DCs are characterized by a highly limiting environment to HIV-1 replication due to the expression of restriction factors as SAMHD1 and APOBEC3G. However, uninfected DCs capture and transfer viral particles to CD4 lymphocytes through a trans-enhancement mechanism in which chemokines are involved...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28122869/a-g1-like-state-allows-hiv-1-to-bypass-samhd1-restriction-in-macrophages
#12
Petra Mlcochova, Katherine A Sutherland, Sarah A Watters, Cosetta Bertoli, Rob Am de Bruin, Jan Rehwinkel, Stuart J Neil, Gina M Lenzi, Baek Kim, Asim Khwaja, Matthew C Gage, Christiana Georgiou, Alexandra Chittka, Simon Yona, Mahdad Noursadeghi, Greg J Towers, Ravindra K Gupta
An unresolved question is how HIV-1 achieves efficient replication in terminally differentiated macrophages despite the restriction factor SAMHD1. We reveal inducible changes in expression of cell cycle-associated proteins including MCM2 and cyclins A, E, D1/D3 in macrophages, without evidence for DNA synthesis or mitosis. These changes are induced by activation of the Raf/MEK/ERK kinase cascade, culminating in upregulation of CDK1 with subsequent SAMHD1 T592 phosphorylation and deactivation of its antiviral activity...
March 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28113112/interplay-between-hiv-1-innate-sensing-and-restriction-in-mucosal-dendritic-cells-balancing-defense-and-viral-transmission
#13
REVIEW
Nina Hertoghs, Teunis B H Geijtenbeek, Carla M S Ribeiro
Innate sensing of HIV-1 by dendritic cells (DCs) initiates cell-intrinsic signalling programs that direct virus restriction and antiviral defenses. These responses include the production of type I interferon (IFN) and a large number of IFN-stimulated genes (ISGs) with a broad spectrum of antiviral effector functions. Initial interactions of HIV-1 at the mucosal surfaces with DC-expressed innate immune factors including cGAS, TRIM5α and SAMHD1 are predictive of viraemia, inflammation and disease pathogenesis...
January 20, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28067901/targeting-samhd1-with-the-vpx-protein-to-improve-cytarabine-therapy-for-hematological-malignancies
#14
Nikolas Herold, Sean G Rudd, Linda Ljungblad, Kumar Sanjiv, Ida Hed Myrberg, Cynthia B J Paulin, Yaser Heshmati, Anna Hagenkort, Juliane Kutzner, Brent D G Page, José M Calderón-Montaño, Olga Loseva, Ann-Sofie Jemth, Lorenzo Bulli, Hanna Axelsson, Bianca Tesi, Nicholas C K Valerie, Andreas Höglund, Julia Bladh, Elisée Wiita, Mikael Sundin, Michael Uhlin, Georgios Rassidakis, Mats Heyman, Katja Pokrovskaja Tamm, Ulrika Warpman-Berglund, Julian Walfridsson, Sören Lehmann, Dan Grandér, Thomas Lundbäck, Per Kogner, Jan-Inge Henter, Thomas Helleday, Torsten Schaller
The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP), which causes DNA damage through perturbation of DNA synthesis. Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/28062478/samhd1-limits-the-effectiveness-of-cytarabine-in-aml
#15
(no author information available yet)
The dNTP triphosphohydrolase SAMHD1 decreases cytarabine (Ara-C) cytotoxicity in AML cells.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28061811/the-nature-and-nurture-of-cell-heterogeneity-accounting-for-macrophage-gene-environment-interactions-with-single-cell-rna-seq
#16
Quin F Wills, Esther Mellado-Gomez, Rory Nolan, Damien Warner, Eshita Sharma, John Broxholme, Benjamin Wright, Helen Lockstone, William James, Mark Lynch, Michael Gonzales, Jay West, Anne Leyrat, Sergi Padilla-Parra, Sarah Filippi, Chris Holmes, Michael D Moore, Rory Bowden
BACKGROUND: Single-cell RNA-Seq can be a valuable and unbiased tool to dissect cellular heterogeneity, despite the transcriptome's limitations in describing higher functional phenotypes and protein events. Perhaps the most important shortfall with transcriptomic 'snapshots' of cell populations is that they risk being descriptive, only cataloging heterogeneity at one point in time, and without microenvironmental context. Studying the genetic ('nature') and environmental ('nurture') modifiers of heterogeneity, and how cell population dynamics unfold over time in response to these modifiers is key when studying highly plastic cells such as macrophages...
January 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28056217/zinc-binding-site-of-hiv-2-vpx-prevents-instability-and-dysfunction-of-the-protein
#17
Minami Yamamoto, Ryoko Koga, Haruna Fujino, Kazunori Shimagaki, Halil Ibrahim Ciftci, Masahiro Kamo, Hiroshi Tateishi, Masami Otsuka, Mikako Fujita
HIV-2 Vpx coordinates zinc through residues H39, H82, C87 and C89. We reported previously that H39, H82 and C87 mutants maintain Vpx activity to facilitate the degradation of SAMHD1. Herein, the expression of Vpx mutants in cells was examined in detail. We demonstrated that the zinc-binding site stabilizes the protein to keep its function in virus growth when low levels of Vpx are expressed. At higher levels of expression, Vpx aggregation can occur, and zinc binding would suppress such aggregation. Among the amino acids involved in zinc coordination, H39 plays the most critical role...
January 5, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28053103/cytokines-elevated-in-hiv-elite-controllers-reduce-hiv-replication-in-vitro-and-modulate-hiv-restriction-factor-expression
#18
Evan S Jacobs, Sheila M Keating, Mohamed Abdel-Mohsen, Stuart L Gibb, John W Heitman, Heather C Inglis, Jeffrey N Martin, Jinbing Zhang, Zhanna Kaidarova, Xutao Deng, Shiquan Wu, Kathryn Anastos, Howard Crystal, Maria C Villacres, Mary Young, Ruth M Greenblatt, Alan L Landay, Stephen J Gange, Steven G Deeks, Elizabeth T Golub, Satish K Pillai, Philip J Norris
A subset of HIV-infected individuals termed elite controllers (ECs) maintain CD4(+) T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28046007/substrates-and-inhibitors-of-samhd1
#19
Joseph A Hollenbaugh, Jadd Shelton, Sijia Tao, Sheida Amiralaei, Peng Liu, Xiao Lu, Russell W Goetze, Longhu Zhou, James H Nettles, Raymond F Schinazi, Baek Kim
SAMHD1 hydrolyzes 2'-deoxynucleoside-5'-triphosphates (dNTPs) into 2'-deoxynucleosides and inorganic triphosphate products. In this paper, we evaluated the impact of 2' sugar moiety substitution for different nucleotides on being substrates for SAMHD1 and mechanisms of actions for the results. We found that dNTPs ((2'R)-2'-H) are only permissive in the catalytic site of SAMHD1 due to L150 exclusion of (2'R)-2'-F and (2'R)-2'-OH nucleotides. However, arabinose ((2'S)-2'-OH) nucleoside-5'-triphosphates analogs are permissive to bind in the catalytic site and be hydrolyzed by SAMHD1...
2017: PloS One
https://www.readbyqxmd.com/read/27991919/samhd1-is-a-biomarker-for-cytarabine-response-and-a-therapeutic-target-in-acute-myeloid-leukemia
#20
Constanze Schneider, Thomas Oellerich, Hanna-Mari Baldauf, Sarah-Marie Schwarz, Dominique Thomas, Robert Flick, Hanibal Bohnenberger, Lars Kaderali, Lena Stegmann, Anjali Cremer, Margarethe Martin, Julian Lohmeyer, Martin Michaelis, Veit Hornung, Christoph Schliemann, Wolfgang E Berdel, Wolfgang Hartmann, Eva Wardelmann, Federico Comoglio, Martin-Leo Hansmann, Alexander F Yakunin, Gerd Geisslinger, Philipp Ströbel, Nerea Ferreirós, Hubert Serve, Oliver T Keppler, Jindrich Cinatl
The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking...
February 2017: Nature Medicine
keyword
keyword
71266
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"