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https://www.readbyqxmd.com/read/29764952/samhd1-phosphorylation-coordinates-the-anti-hiv-1-response-by-diverse-interferons-and-tyrosine-kinase-inhibition
#1
Matthew A Szaniawski, Adam M Spivak, James E Cox, Jonathan L Catrow, Timothy Hanley, Elizabeth S C P Williams, Michel J Tremblay, Alberto Bosque, Vicente Planelles
Macrophages are susceptible to human immunodeficiency virus type 1 (HIV-1) infection despite abundant expression of antiviral proteins. Perhaps the most important antiviral protein is the restriction factor sterile alpha motif domain and histidine/aspartic acid domain-containing protein 1 (SAMHD1). We investigated the role of SAMHD1 and its phospho-dependent regulation in the context of HIV-1 infection in primary human monocyte-derived macrophages and the ability of various interferons (IFNs) and pharmacologic agents to modulate SAMHD1...
May 15, 2018: MBio
https://www.readbyqxmd.com/read/29753769/fish-samhd1-performs-as-an-activator-for-ifn-expression
#2
Meifeng Li, Xiaowen Xu, Zeyin Jiang, Changxin Liu, Xiao Shi, Guoqin Qi, Yinping Li, Xin Chen, Qingli Huang, Huiling Mao, Chengyu Hu
As a host limiting factor, Sterile Alpha Motif and Histidine-Aspartate Domain 1 protein (SAMHD1) is associated with IRF3-mediated antiviral and apoptotic responses in mammals. However, the antiviral mechanism of SAMHD1 remains indistinct in fish. In this study, we found the expression of Ctenopharyngodon idella SAMHD1 (MF326081) was up-regulated after transfection with poly I:C (dsRNA analog), B-DNA or Z-DNA into C. idella kidney cells (CIKs), but these expression profiles had no obvious change when the cells were incubated with these nucleic acids...
May 10, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29745378/correction-to-the-samhd1-mediated-block-of-line-1-retroelements-is-regulated-by-phosphorylation
#3
A Herrmann, S Wittmann, D Thomas, C N Shepard, B Kim, N Ferreirós, T Gramberg
[This corrects the article DOI: 10.1186/s13100-018-0116-5.].
2018: Mobile DNA
https://www.readbyqxmd.com/read/29740948/astrocytes-an-active-player-in-aicardi-gouti%C3%A3-res-syndrome
#4
Sunetra Sase, Asako Takanohashi, Adeline Vanderver, Akshata Almad
Aicardi-Goutières syndrome (AGS) is an early-onset, autoimmune and genetically heterogeneous disorder with severe neurologic injury. Molecular studies have established that autosomal recessive mutations in one of the following genes are causative: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 and IFIH1/MDA5. The phenotypic presentation and pathophysiology of AGS is associated with over-production of the cytokine Interferon-alpha (IFN-α) and its downstream signaling, characterized as type I interferonopathy...
May 2018: Brain Pathology
https://www.readbyqxmd.com/read/29722257/graphene-oxide-facilitated-comprehensive-analysis-of-cellular-nucleic-acid-binding-proteins-for-lung-cancer
#5
Zhi Shang, Liqiang Qian, Sha Liu, Xiaomin Niu, Zhi Qiao, Yan Sun, Yan Zhang, Liu-Yin Fan, Xin Guan, Cheng-Xi Cao, Hua Xiao
Nucleic acid binding proteins (NABPs) mediate a broad range of essential cellular functions. However, it is very challenging to comprehensively extract whole cellular NABPs due to the lack of approaches with high efficiency. To this end, carbon nanomaterials, including Graphene Oxide (GO), Carboxylated Graphene (cG), and Carboxylated Carbon Nanotube (cCNT), were utilized to extract cellular NABPs in this study through a new strategy. Our data demonstrated that GO, cG, and cCNT could extract nearly 100% cellular DNA in vitro...
May 3, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29703825/-samhd1-mutations-disrupt-replication-fork-progression-to-induce-ifn
#6
(no author information available yet)
SAMHD1 activates MRE11 exonuclease activity to prevent release of ssDNA from stalled replication forks.
April 27, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29698322/lentiviral-infection-of-proliferating-brain-macrophages-in-hiv-and-simian-immunodeficiency-virus-encephalitis-despite-sterile-alpha-motif-and-histidine-aspartate-domain-containing-protein-1-expression
#7
Allison A Lindgren, Adam R Filipowicz, Julian B Hattler, Soon Ok Kim, Hye Kyung Chung, Marcelo J Kuroda, Edward M Johnson, Woong-Ki Kim
OBJECTIVE: HIV-1 infection of the brain and related cognitive impairment remain prevalent in HIV-1-infected individuals despite combination antiretroviral therapy. Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a newly identified host restriction factor that blocks the replication of HIV-1 and other retroviruses in myeloid cells. Cell cycle-regulated phosphorylation at residue Thr592 and viral protein X (Vpx)-mediated degradation of SAMHD1 have been shown to bypass SAMHD1 restriction in vitro...
May 15, 2018: AIDS
https://www.readbyqxmd.com/read/29670289/samhd1-acts-at-stalled-replication-forks-to-prevent-interferon-induction
#8
Flavie Coquel, Maria-Joao Silva, Hervé Técher, Karina Zadorozhny, Sushma Sharma, Jadwiga Nieminuszczy, Clément Mettling, Elodie Dardillac, Antoine Barthe, Anne-Lyne Schmitz, Alexy Promonet, Alexandra Cribier, Amélie Sarrazin, Wojciech Niedzwiedz, Bernard Lopez, Vincenzo Costanzo, Lumir Krejci, Andrei Chabes, Monsef Benkirane, Yea-Lih Lin, Philippe Pasero
SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi-Goutières syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR-CHK1 checkpoint and allows the forks to restart replication...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29669924/samhd1-enhances-immunoglobulin-hypermutation-by-promoting-transversion-mutation
#9
Eddy Sanchai Thientosapol, Daniel Bosnjak, Timothy Durack, Igor Stevanovski, Michelle van Geldermalsen, Jeff Holst, Zeenat Jahan, Caitlin Shepard, Wolfgang Weninger, Baek Kim, Robert Brink, Christopher J Jolly
Activation-induced deaminase (AID) initiates hypermutation of Ig genes in activated B cells by converting C:G into U:G base pairs. G1 -phase variants of uracil base excision repair (BER) and mismatch repair (MMR) then deploy translesion polymerases including REV1 and Pol η, which exacerbates mutation. dNTP paucity may contribute to hypermutation, because dNTP levels are reduced in G1 phase to inhibit viral replication. To derestrict G1 -phase dNTP supply, we CRISPR-inactivated SAMHD1 (which degrades dNTPs) in germinal center B cells...
April 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29614270/dna-damage-response-signaling-does-not-trigger-redistribution-of-samhd1-to-nuclear-foci
#10
Ana Carla Medeiros, Claudia S Soares, Priscila O Coelho, Nichelle A Vieira, Munira M A Baqui, Felipe R Teixeira, Marcelo D Gomes
SAMHD1 (Sterile alpha motif and histidine-aspartic acid (HD) domain containing protein 1) is a deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase (dNTPase) that restricts viral replication in infected cells. This protein is also involved in DNA repair by assisting in DNA end resection by homologous recombination (HR) after DNA double-strand break (DSB) induction with camptothecin (CPT) or etoposide (ETO). We showed that a monoclonal anti-SAMHD1 antibody produced against the full-length protein detected an unspecific 50 kDa protein that colocalized with dot-like structures after CPT treatment in HeLa cells...
March 31, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29610582/the-samhd1-mediated-block-of-line-1-retroelements-is-regulated-by-phosphorylation
#11
Alexandra Herrmann, Sabine Wittmann, Dominique Thomas, Caitlin N Shepard, Baek Kim, Nerea Ferreirós, Thomas Gramberg
Background: The restriction factor SAMHD1 regulates intracellular nucleotide level by degrading dNTPs and blocks the replication of retroviruses and DNA viruses in non-cycling cells, like macrophages or dendritic cells. In patients, inactivating mutations in samhd1 are associated with the autoimmune disease Aicardi-Goutières Syndrome (AGS). The accumulation of intracellular nucleic acids derived from endogenous retroelements thriving in the absence of SAMHD1 has been discussed as potential trigger of the autoimmune reaction...
2018: Mobile DNA
https://www.readbyqxmd.com/read/29610295/samhd1-suppresses-innate-immune-responses-to-viral-infections-and-inflammatory-stimuli-by-inhibiting-the-nf-%C3%AE%C2%BAb-and-interferon-pathways
#12
Shuliang Chen, Serena Bonifati, Zhihua Qin, Corine St Gelais, Karthik M Kodigepalli, Bradley S Barrett, Sun Hee Kim, Jenna M Antonucci, Katherine J Ladner, Olga Buzovetsky, Kirsten M Knecht, Yong Xiong, Jacob S Yount, Denis C Guttridge, Mario L Santiago, Li Wu
Sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) blocks replication of retroviruses and certain DNA viruses by reducing the intracellular dNTP pool. SAMHD1 has been suggested to down-regulate IFN and inflammatory responses to viral infections, although the functions and mechanisms of SAMHD1 in modulating innate immunity remain unclear. Here, we show that SAMHD1 suppresses the innate immune responses to viral infections and inflammatory stimuli by inhibiting nuclear factor-κB (NF-κB) activation and type I interferon (IFN-I) induction...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29594836/molecular-dynamics-characterization-of-the-samhd1-aicardi-gouti%C3%A3-res-arg145gln-mutant-structural-determinants-for-the-impaired-tetramerization
#13
Francesca Cardamone, Mattia Falconi, Alessandro Desideri
Aicardi-Goutières syndrome, a rare genetic disorder characterized by calcification of basal ganglia, results in psychomotor delays and epilepsy states from the early months of children life. This disease is caused by mutations in seven different genes encoding proteins implicated in the metabolism of nucleic acids, including SAMHD1. Twenty SAMHD1 gene variants have been discovered and in this work, a structural characterization of the SAMHD1 Aicardi-Goutières Arg145Gln mutant is reported by classical molecular dynamics simulation...
March 28, 2018: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29587790/inhibition-of-hiv-early-replication-by-the-p53-and-its-downstream-gene-p21
#14
Binshan Shi, Hamayun J Sharifi, Sara DiGrigoli, Michaela Kinnetz, Katie Mellon, Wenwei Hu, Carlos M C de Noronha
BACKGROUND: The tumor suppressor gene p53 has been found to suppress HIV infection by various mechanisms, but the inhibition of HIV at an early stage of replication by host cell p53 and its downstream gene p21 has not been well studied. METHOD: VSV-G pseudotyped HIV-1 or HIV-2 viruses with GFP or luciferase reporter gene were used to infect HCT116 p53+/+ cells, HCT116 p53-/- cells and hMDMs. The infections were detected by flow cytometry or measured by luciferase assay...
March 27, 2018: Virology Journal
https://www.readbyqxmd.com/read/29583030/samhd1-recurring-roles-in-cell-cycle-viral-restriction-cancer-and-innate-immunity
#15
Christopher H Mauney, Thomas Hollis
Sterile alpha motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) is a deoxynucleotide triphosphate (dNTP) hydrolase that plays an important role in the homeostatic balance of cellular dNTPs. Its emerging role as an effector of innate immunity is affirmed by mutations in the SAMHD1 gene that cause the severe autoimmune disease, Aicardi-Goutieres syndrome (AGS) and that are linked to cancer. Additionally, SAMHD1 functions as a restriction factor for retroviruses, such as HIV. Here, we review the current biochemical and biological properties of the enzyme including its structure, activity, and regulation by post-translational modifications in the context of its cellular function...
March 27, 2018: Autoimmunity
https://www.readbyqxmd.com/read/29554922/a-crispr-screen-for-factors-regulating-samhd1-degradation-identifies-ifitms-as-potent-inhibitors-of-lentiviral-particle-delivery
#16
Ferdinand Roesch, Molly OhAinle, Michael Emerman
The InterFeron Induced TransMembrane (IFITM) proteins are interferon stimulated genes that restrict many viruses, including HIV-1. SAMHD1 is another restriction factor blocking replication of HIV-1 and other viruses. Some lentiviruses evolved Vpx/Vpr proteins to degrade SAMHD1. However, this viral antagonism can be perturbed by host mechanisms: a recent study showed that in interferon (IFN) treated THP1 cells, Vpx is unable to degrade SAMHD1. In the present work, we designed an Interferon Stimulated Genes (ISGs)-targeted CRISPR knockout screen in order to identify ISGs regulating this phenotype...
March 20, 2018: Retrovirology
https://www.readbyqxmd.com/read/29547435/lentiviral-infection-of-proliferating-brain-macrophages-in-siv-and-hiv-encephalitis-despite-samhd1-expression
#17
Allison A Lindgren, Adam R Filipowicz, Julian B Hattler, Soon Ok Kim, Hye Kyung Chung, Marcelo J Kuroda, Edward M Johnson, Woong-Ki Kim
OBJECTIVE: HIV-1 infection of the brain and related cognitive impairment remain prevalent in HIV-1-infected subjects despite combination antiretroviral therapy. Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is a newly identified host restriction factor that blocks the replication of HIV-1 and other retroviruses in myeloid cells. Cell-cycle-regulated phosphorylation at residue Thr592 and viral protein X (Vpx)-mediated degradation of SAMHD1 have been shown to bypass SAMHD1 restriction in vitro...
March 15, 2018: AIDS
https://www.readbyqxmd.com/read/29515139/dna-damage-induces-a-samhd1-mediated-block-to-the-infection-of-macrophages-by-hiv-1
#18
Paula Jáuregui, Nathaniel R Landau
Monocyte-derived macrophages (MDMs) are an important target for HIV-1 despite SAMHD1, a myeloid restriction factor for which HIV-1 lacks a counteracting accessory protein. The antiviral activity of SAMHD1 is modulated by phosphorylation of T592 by cyclin-dependent kinases (CDK). We show that treatment of MDMs with neocarzinostatin, a compound that introduces double strand breaks (DBS) in genomic DNA, results in the decrease of phosphorylated SAMHD1, activating its antiviral activity and blocking HIV-1 infection...
March 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29465030/novel-host-restriction-factors-implicated-in-hiv-1-replication
#19
Dibya Ghimire, Madhu Rai, Ritu Gaur
Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction...
April 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29379009/the-sam-domain-of-mouse-samhd1-is-critical-for-its-activation-and-regulation
#20
Olga Buzovetsky, Chenxiang Tang, Kirsten M Knecht, Jenna M Antonucci, Li Wu, Xiaoyun Ji, Yong Xiong
Human SAMHD1 (hSAMHD1) is a retroviral restriction factor that blocks HIV-1 infection by depleting the cellular nucleotides required for viral reverse transcription. SAMHD1 is allosterically activated by nucleotides that induce assembly of the active tetramer. Although the catalytic core of hSAMHD1 has been studied extensively, previous structures have not captured the regulatory SAM domain. Here we report the crystal structure of full-length SAMHD1 by capturing mouse SAMHD1 (mSAMHD1) structures in three different nucleotide bound states...
January 29, 2018: Nature Communications
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