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https://www.readbyqxmd.com/read/29100097/monogenic-lupus-it-s-all-new
#1
REVIEW
Patricia Costa-Reis, Kathleen E Sullivan
Monogenic lupus is rare, but its study has contributed immensely to a better understanding of the pathogenesis of systemic lupus erythematosus. The first forms identified were inherited complement deficiencies, which predisposed to lupus due to impaired tolerance, and aberrant clearance of apoptotic bodies and immune complexes. In recent years, several new monogenic disorders with a lupus-like phenotype have been described. These include forms that affect nucleic acid repair, degradation and sensing (TREX1, DNASE1L3), the type I interferon (IFN) pathway (SAMHD1, RNASEH2ABC, ADAR1, IFIH1, ISG15, ACP5, TMEM173) and B cell development checkpoints (PRKCD; RAG2)...
October 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28978134/samhd1-acetylation-enhances-its-deoxynucleotide-triphosphohydrolase-activity-and-promotes-cancer-cell-proliferation
#2
Eun Ji Lee, Ji Hae Seo, Ji-Hyeon Park, Tam Thuy Lu Vo, Sunho An, Sung-Jin Bae, Hoang Le, Hye Shin Lee, Hee-Jun Wee, Danbi Lee, Young-Hwa Chung, Jeong A Kim, Myoung-Kuk Jang, Soo Hyung Ryu, Ensil Yu, Se Hwan Jang, Zee Yong Park, Kyu-Won Kim
SAM domain and HD domain containing protein 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase (dNTPase) that inhibits retroviruses by depleting intracellular deoxynucleotide triphosphates (dNTPs) in non-cycling myeloid cells. Although SAMHD1 is expressed ubiquitously throughout the human body, the molecular mechanisms regulating its enzymatic activity and function in non-immune cells are relatively unexplored. Here, we demonstrate that the dNTPase activity of SAMHD1 is regulated by acetylation, which promotes cell cycle progression in cancer cells...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977405/genome-scale-detection-of-positive-selection-in-nine-primates-predicts-human-virus-evolutionary-conflicts
#3
Robin van der Lee, Laurens Wiel, Teunis J P van Dam, Martijn A Huynen
Hotspots of rapid genome evolution hold clues about human adaptation. We present a comparative analysis of nine whole-genome sequenced primates to identify high-confidence targets of positive selection. We find strong statistical evidence for positive selection in 331 protein-coding genes (3%), pinpointing 934 adaptively evolving codons (0.014%). Our new procedure is stringent and reveals substantial artefacts (20% of initial predictions) that have inflated previous estimates. The final 331 positively selected genes (PSG) are strongly enriched for innate and adaptive immunity, secreted and cell membrane proteins (e...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28969870/samhd1-sheds-moonlight-on-dna-double-strand-break-repair
#4
Maria Jose Cabello-Lobato, Siyue Wang, Christine Katrin Schmidt
SAMHD1 (sterile α motif and histidine (H) aspartate (D) domain-containing protein 1) is known for its antiviral activity of hydrolysing deoxynucleotides required for virus replication. Daddacha et al. identify a hydrolase-independent, moonlighting function of SAMHD1 that facilitates homologous recombination of DNA double-strand breaks (DSBs) by promoting recruitment of C-terminal binding protein interacting protein (CTIP), a DNA-end resection factor, to damaged DNA. These findings could benefit anticancer treatment...
September 29, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28956603/allosteric-signal-transduction-in-hiv-1-restriction-factor-samhd1-proceeds-via-reciprocal-handshake-across-monomers
#5
Kajwal Kumar Patra, Akash Bhattacharya, Swati Bhattacharya
The sterile alpha motif and histidine-aspartate domain-containing protein 1 (or SAMHD1), a human dNTP-triphosphohydrolase, contributes to HIV-1 restriction in select terminally differentiated cells of the immune system. The catalytically active form of the protein is an allosterically triggered tetramer, whose HIV-1 restriction properties are attributed to its dNTP-triphosphohydrolase activity. The tetramer itself is assembled by a GTP/dNTP combination. This enzyme uses the strategy of deoxynucleotide starvation, which is thought to prevent effective reverse transcription of the retroviral genome-hence, restricting HIV-1 propagation...
October 23, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28953327/t-cells-with-low-cd2-levels-express-reduced-restriction-factors-and-are-preferentially-infected-in-therapy-na%C3%A3-ve-chronic-hiv-1-patients
#6
Sebastian Bolduan, Herwig Koppensteiner, Ramona Businger, Stephanie Rebensburg, Christine Kunze, Ruth Brack-Werner, Rika Draenert, Michael Schindler
INTRODUCTION: Restriction factors (RFs) suppress HIV-1 in cell lines and primary cell models. Hence, RFs might be attractive targets for novel antiviral strategies, but their importance for virus control in vivo is controversial. METHODS: We profiled the expression of RFs in primary blood-derived mononuclear cells (PBMC) from therapy-naïve HIV-1 patients and quantified infection. RESULTS: Overall, there was no correlation between individual RF expression and HIV-1 status in total PBMC...
September 19, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28935667/upregulation-of-human-endogenous-retrovirus-k-is-linked-to-immunity-and-inflammation-in-pulmonary-arterial-hypertension
#7
Toshie Saito, Kazuya Miyagawa, Shih-Yu Chen, Rasa Tamosiuniene, Lingli Wang, Orr Sharpe, Erik Samayoa, Daisuke Harada, Jan-Renier A J Moonen, Aiqin Cao, Pin-I Chen, Jan K Hennigs, Mingxia Gu, Caiyun G Li, Ryan D Leib, Dan Li, Christopher M Adams, Patricia A Del Rosario, Matthew Bill, Francois Haddad, Jose G Montoya, William H Robinson, Wendy J Fantl, Garry P Nolan, Roham T Zamanian, Mark R Nicolls, Charles Y Chiu, Maria E Ariza, Marlene Rabinovitch
BACKGROUND: Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, and connected in the progression of disease. We therefore set out to identify specific target antigens in PAH lung immune complexes as a starting point toward resolving these issues to better inform future application of immunomodulatory therapies...
November 14, 2017: Circulation
https://www.readbyqxmd.com/read/28931685/p21-restricts-hiv-1-in-monocyte-derived-dendritic-cells-through-the-reduction-of-deoxynucleoside-triphosphate-biosynthesis-and-regulation-of-samhd1-antiviral-activity
#8
Jose Carlos Valle-Casuso, Awatef Allouch, Annie David, Gina M Lenzi, Lydia Studdard, Françoise Barré-Sinoussi, Michaela Müller-Trutwin, Baek Kim, Gianfranco Pancino, Asier Sáez-Cirión
HIV-1 infection of noncycling cells, such as dendritic cells (DCs), is impaired due to limited availability of deoxynucleoside triphosphates (dNTPs), which are needed for HIV-1 reverse transcription. The levels of dNTPs are tightly regulated during the cell cycle and depend on the balance between dNTP biosynthesis and degradation. SAMHD1 potently blocks HIV-1 replication in DCs, although the underlying mechanism is still unclear. SAMHD1 has been reported to be able to degrade dNTPs and viral nucleic acids, which may both hamper HIV-1 reverse transcription...
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28884867/uncovering-allostery-and-regulation-in-samhd1-through-molecular-dynamics-simulations
#9
Kajwal Kumar Patra, Akash Bhattacharya, Swati Bhattacharya
No abstract text is available yet for this article.
October 2017: Proteins
https://www.readbyqxmd.com/read/28871089/cd81-association-with-samhd1-enhances-hiv-1-reverse-transcription-by-increasing-dntp-levels
#10
Vera Rocha-Perugini, Henar Suárez, Susana Álvarez, Soraya López-Martín, Gina M Lenzi, Felipe Vences-Catalán, Shoshana Levy, Baek Kim, María A Muñoz-Fernández, Francisco Sánchez-Madrid, Maria Yáñez-Mó
In this study, we report that the tetraspanin CD81 enhances human immunodeficiency virus (HIV)-1 reverse transcription in HIV-1-infected cells. This is enabled by the direct interaction of CD81 with the deoxynucleoside triphosphate phosphohydrolase SAMHD1. This interaction prevents endosomal accumulation and favours the proteasome-dependent degradation of SAMHD1. Consequently, CD81 depletion results in SAMHD1 increased expression, decreasing the availability of deoxynucleoside triphosphates (dNTP) and thus HIV-1 reverse transcription...
November 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28851465/samhd1-mutations-are-also-responsible-for-aicardi-gouti%C3%A3-res-in-the-cree-population
#11
Ashraf Kharrat, Jennifer MacKenzie, Sunita Venkateswaran
No abstract text is available yet for this article.
August 30, 2017: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
https://www.readbyqxmd.com/read/28844088/familial-chilblain-lupus-what-can-we-learn-from-type-i-interferonopathies
#12
REVIEW
Christoph Fiehn
PURPOSE OF REVIEW: Familial chilblain lupus belongs to the group of type I interferonopathies and is characterized by typical skin manifestations and acral ischaemia. This review aims to give an overview of clinical signs and the pathophysiological mechanisms. RECENT FINDINGS: There are several mutations that can lead to this autosomal dominant disease. Most frequent is a mutation of the gene for TREX-1. However, as well cases of families with mutations in the SAMHD1 gene and, recently, with one for the gene that codes for the protein stimulator of interferon genes have been described...
August 26, 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28834754/samhd1-promotes-dna-end-resection-to-facilitate-dna-repair-by-homologous-recombination
#13
Waaqo Daddacha, Allyson E Koyen, Amanda J Bastien, PamelaSara E Head, Vishal R Dhere, Geraldine N Nabeta, Erin C Connolly, Erica Werner, Matthew Z Madden, Michele B Daly, Elizabeth V Minten, Donna R Whelan, Ashley J Schlafstein, Hui Zhang, Roopesh Anand, Christine Doronio, Allison E Withers, Caitlin Shepard, Ranjini K Sundaram, Xingming Deng, William S Dynan, Ya Wang, Ranjit S Bindra, Petr Cejka, Eli Rothenberg, Paul W Doetsch, Baek Kim, David S Yu
DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-inducing agents, and SAMHD1 is recruited to DSBs...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28814521/hiv-fusion-in-dendritic-cells-occurs-mainly-at-the-surface-and-is-limited-by-low-cd4-levels
#14
Lise Chauveau, Daniel Aaron Donahue, Blandine Monel, Francoise Porrot, Timothée Bruel, Lea Richard, Nicoletta Casartelli, Olivier Schwartz
HIV-1 poorly infects monocyte-derived dendritic cells (MDDCs). This is in large part due to SAMHD1, which restricts viral reverse transcription. Pseudotyping HIV-1 with vesicular stomatitis virus G protein (VSV-G) strongly enhances infection, suggesting that earlier steps of viral replication, including fusion, are also inefficient in MDDCs. The site of HIV-1 fusion remains controversial and may depend on the cell type, with reports indicating that it occurs at the plasma membrane or, conversely, in an endocytic compartment...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28803141/the-poly-proline-tail-of-sivmac-vpx-provides-gain-of-function-for-resistance-to-a-cryptic-proteasome-dependent-degradation-pathway
#15
Nannan Zhang, Haoran Guo, Jiaxin Yang, Guanchen Liu, Shuang Li, Siying Li, Dongyin Wang, Rui Li, Chang Shu, Hongmei Xu, Zhentong Wei, Honglan Huang, Songling Zhang, Pujun Gao, Shan Cen, Richard Markham, Yongsheng Wang, Xiao-Fang Yu, Wei Wei
The lentiviral accessory protein Vpx is critical for viral infection of myeloid cells and acts by hijacking CRL4(DCAF1) E3 ubiquitin ligase to induce the degradation of the host restriction factor SAMHD1. It has been observed that the sequences from HIV-2 and SIVsmm/SIVmac Vpx contain a poly-proline tail which is distinct from other SIV Vpx proteins. However, the role of this region in Vpx function is controversial. Herein, we found proteasome-dependent degradation of a Vpx mutant lacking the poly-proline tail in the nucleus in a CRL4(DCAF1) E3 ligase-independent fashion...
November 2017: Virology
https://www.readbyqxmd.com/read/28793904/the-impact-of-p53-on-the-early-stage-replication-of-retrovirus
#16
Michaela Kinnetz, Faris Alghamdi, Michael Racz, Wenwei Hu, Binshan Shi
BACKGROUND: The function of p53 in cancer biology has been studied extensively, but its role in anti-retrovirus infection has been elusive for many years. The restriction of retrovirus early stage replication by p53 was investigated in this study. METHOD: VSV-G pseudotyped retrovirus with GFP reporter gene was used to infect both HCT116 p53(+/+) cells and its isogenic p53 knockout HCT116 p53(-/-) cells. The infection was detected by flow cytometry. Reverse transcription products were quantified by real time PCR...
August 9, 2017: Virology Journal
https://www.readbyqxmd.com/read/28685292/role-of-innate-genes-in-hiv-replication
#17
Kerstin Schott, Maximilian Riess, Renate König
Cells use an elaborate innate immune surveillance and defense system against virus infections. Here, we discuss recent studies that reveal how HIV-1 is sensed by the innate immune system. Furthermore, we present mechanisms on the counteraction of HIV-1. We will provide an overview how HIV-1 actively utilizes host cellular factors to avoid sensing. Additionally, we will summarize effectors of the innate response that provide an antiviral cellular state. HIV-1 has evolved passive mechanism to avoid restriction and to regulate the innate response...
July 8, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28586337/corrigendum-samhd1-is-a-biomarker-for-cytarabine-response-and-a-therapeutic-target-in-acute-myeloid-leukemia
#18
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
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28584254/whole-genome-sequencing-of-chronic-lymphocytic-leukemia-reveals-distinct-differences-in-the-mutational-landscape-between-ighv-mut-and-ighv-unmut-subgroups
#19
A Burns, R Alsolami, J Becq, A Timbs, D Bruce, P Robbe, D Vavoulis, M Cabes, H Dreau, J Taylor, S J L Knight, R Mansson, D Bentley, R Beekman, J I Martín-Subero, E Campo, R S Houlston, K E Ridout, A Schuh
Chronic lymphocytic leukemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance of somatic hypermutation (SHM) affecting the Ig variable heavy chain locus (IgHV). The molecular mechanisms underlying these subtypes are incompletely understood. Here, we present a comprehensive whole genome sequencing (WGS) analysis of somatically acquired genetic events from 46 CLL patients, including a systematic comparison of coding and non-coding SNVs, CNVs and structural variants, regions of kataegis and mutation signatures between IgHV(mut) and IgHV(unmut) subtypes...
June 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28502830/with-me-or-against-me-tumor-suppressor-and-drug-resistance-activities-of-samhd1
#20
Nikolas Herold, Sean G Rudd, Kumar Sanjiv, Juliane Kutzner, Ida Hed Myrberg, Cynthia B J Paulin, Thale Kristin Olsen, Thomas Helleday, Jan-Inge Henter, Torsten Schaller
Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) is a (deoxy)guanosine triphosphate (dGTP/GTP)-activated deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase involved in cellular dNTP homoeostasis. Mutations in SAMHD1 have been associated with the hyperinflammatory disease Aicardi-Goutières syndrome (AGS). SAMHD1 also limits cells' permissiveness to infection with diverse viruses, including human immunodeficiency virus (HIV-1), and controls endogenous retroviruses...
August 2017: Experimental Hematology
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