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Endogenous retrovirus

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https://www.readbyqxmd.com/read/29774579/integrative-epigenetic-analysis-reveals-therapeutic-targets-to-the-dna-methyltransferase-inhibitor-sgi-110-in-hepatocellular-carcinoma
#1
Minmin Liu, Lian Zhang, Hongtao Li, Toshinori Hinoue, Wanding Zhou, Hitoshi Ohtani, Anthony El-Khoueiry, John Daniels, Casey O'Connell, Tanya B Dorff, Qianjin Lu, Daniel J Weisenberger, Gangning Liang
There is an urgent need for developing more effective therapies for hepatocellular carcinoma (HCC) because of its aggressiveness. Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi) currently in clinical trials for HCC and shows greater stability and performance over first generation DNMTis. In order to identify potential therapeutic targets of SGI-110 for clinical trials, HCC cell lines (SNU398, HepG2 and SNU475) were used to evaluate effects of transient SGI-110 treatment by an integrative analysis of DNA methylation, nucleosome accessibility, gene expression profiles and its clinical relevance by comparisons to TCGA HCC clinical data...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774123/the-association-of-human-endogenous-retrovirus-h-long-terminal-repeat-associating-protein-2-hhla2-expression-with-gastric-cancer-prognosis
#2
Masataka Shimonosono, Takaaki Arigami, Shigehiro Yanagita, Daisuke Matsushita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Yoshikazu Uenosono, Sumiya Ishigami, Shoji Natsugoe
Currently, immune checkpoint blockade against members of the B7/CD28 family is being used as a new molecular-targeted therapy, in patients with unresectable advanced or recurrent gastric cancer. Although human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel molecule of the B7/CD28 family, the clinical impact of its expression remains uncertain in gastric cancer. Consequently, we examined HHLA2 expression in blood specimens from patients with gastric cancer, and investigated the relationship between its expression and clinicopathological factors to assess its potential power as a prognostic blood predictor...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29772310/recombination-activity-of-human-rag2-mutations-and-correlation-with-the-clinical-phenotype
#3
Irit Tirosh, Yasuhiro Yamazaki, Francesco Frugoni, Francesca A Ververs, Eric J Allenspach, Yu Zhang, Siobhan Burns, Waleed Al-Herz, Lenora Noroski, Jolan E Walter, Andrew R Gennery, Mirjam van der Burg, Luigi D Notarangelo, Yu Nee Lee
BACKGROUND: Mutations in the Recombinase Activating Gene 1 and 2 (RAG1, RAG2) are associated with a broad range of clinical and immunological phenotypes in humans. OBJECTIVE: Using a flow cytometry-based assay, we aimed to measure the recombinase activity of naturally occurring RAG2 mutant proteins, and to correlate results with the severity of the clinical and immunological phenotype. METHODS: Abelson virus-transformed Rag2-/- pro-B cells engineered to contain an inverted GFP cassette flanked by recombination signal sequences (RSS) were transduced with retroviruses encoding either wild-type or 41 naturally occurring RAG2 variants...
May 14, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29760455/substrate-sequence-selectivity-of-apobec3a-implicates-intra-dna-interactions
#4
Tania V Silvas, Shurong Hou, Wazo Myint, Ellen Nalivaika, Mohan Somasundaran, Brian A Kelch, Hiroshi Matsuo, Nese Kurt Yilmaz, Celia A Schiffer
The APOBEC3 (A3) family of human cytidine deaminases is renowned for providing a first line of defense against many exogenous and endogenous retroviruses. However, the ability of these proteins to deaminate deoxycytidines in ssDNA makes A3s a double-edged sword. When overexpressed, A3s can mutate endogenous genomic DNA resulting in a variety of cancers. Although the sequence context for mutating DNA varies among A3s, the mechanism for substrate sequence specificity is not well understood. To characterize substrate specificity of A3A, a systematic approach was used to quantify the affinity for substrate as a function of sequence context, length, secondary structure, and solution pH...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29755432/murine-endogenous-retroviruses-are-detectable-in-patient-derived-xenografts-but-not-in-patient-individual-cell-lines-of-human-colorectal-cancer
#5
Stephanie Bock, Christina S Mullins, Ernst Klar, Philippe Pérot, Claudia Maletzki, Michael Linnebacher
Endogenous retroviruses are remnants of retroviral infections. In contrast to their human counterparts, murine endogenous retroviruses (mERV) still can synthesize infectious particles and retrotranspose. Xenotransplanted human cells have occasionally been described to be mERV infected. With genetic engineered mice and patient-derived xenografts (PDXs) on the rise as eminent research tools, we here systematically investigated, if different tumor models harbor mERV infections. Relevant mERV candidates were first preselected by next generation sequencing (NGS) analysis of spontaneous lymphomas triggered by colorectal cancer (CRC) PDX tissue...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29755422/porcine-endogenous-retrovirus-perv-molecular-structure-and-replication-strategy-in-the-context-of-retroviral-infection-risk-of-human-cells
#6
REVIEW
Krzysztof Łopata, Emilia Wojdas, Roman Nowak, Paweł Łopata, Urszula Mazurek
The xenotransplantation of porcine tissues may help overcome the shortage of human organs for transplantation. However, there are some concerns about recipient safety because the risk of porcine endogenous retrovirus (PERV) transmission to human cells remains unknown. Although, to date, no PERV infections have been noted in vivo , the possibility of such infections has been confirmed in vitro . Better understanding of the structure and replication cycle of PERVs is a prerequisite for determining the risk of infection and planning PERV-detection strategies...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29749030/a-new-therapeutic-approach-for-type-1-diabetes-rationale-for-gnbac1-an-anti-herv-w-env-monoclonal-antibody
#7
REVIEW
Francois Curtin, Corinne Bernard, Sandrine Levet, Hervé Perron, Hervé Porchet, Julie Médina, Sam Malpass, David Lloyd, Richard Simpson
We describe a newly identified therapeutic target for type 1 diabetes: an envelope protein of endogenous retroviral origin called Human Endogenous Retrovirus W Envelope (HERV-W-Env). HERV-W-Env was found to be detected in the blood of around 60% of type 1 diabetes (T1D) patients and is expressed in acinar pancreatic cells of 75% of T1D patients at post-mortem examination. Preclinical experiments showed that this protein displays direct cytotoxicity on human β-islet cells. In vivo HERV-W-Env impairs the insulin and glucose metabolism in transgenic mice expressing HERV-W-Env...
May 10, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29743957/the-case-for-not-masking-away-repetitive-dna
#8
EDITORIAL
R Keith Slotkin
In the course of analyzing whole-genome data, it is common practice to mask or filter out repetitive regions of a genome, such as transposable elements and endogenous retroviruses, in order to focus only on genes and thus simplify the results. This Commentary is a plea from one member of the Mobile DNA community to all gene-centric researchers: please do not ignore the repetitive fraction of the genome . Please stop narrowing your findings by only analyzing a minority of the genome, and instead broaden your analyses to include the rich biology of repetitive and mobile DNA...
2018: Mobile DNA
https://www.readbyqxmd.com/read/29743595/transactivation-of-human-endogenous-retrovirus-k-herv-k-by-kshv-promotes-kaposi-s-sarcoma-development
#9
Lu Dai, Luis Del Valle, Wendell Miley, Denise Whitby, Augusto C Ochoa, Erik K Flemington, Zhiqiang Qin
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of several human cancers such as Kaposi's sarcoma (KS), which represents the most common AIDS-associated malignancy that lacks effective treatment options. Despite its clear role in AIDS malignancies, the fact that only a small set of KSHV-infected patients will eventually develop these tumors implies that additional co-factors are required for the development of KSHV-related cancers. In the current study, we demonstrate for the first time that KSHV de novo infection or viral latent proteins are able to transactivate human endogenous retrovirus K (HERV-K) through a variety of cellular signaling pathways and transcriptional factors...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29728652/defective-germline-reprogramming-rewires-the-spermatogonial-transcriptome
#10
Lina Vasiliauskaitė, Rebecca V Berrens, Ivayla Ivanova, Claudia Carrieri, Wolf Reik, Anton J Enright, Dónal O'Carroll
Defective germline reprogramming in Piwil4 (Miwi2)- and Dnmt3l-deficient mice results in the failure to reestablish transposon silencing, meiotic arrest and progressive loss of spermatogonia. Here we sought to understand the molecular basis for this spermatogonial dysfunction. Through a combination of imaging, conditional genetics and transcriptome analysis, we demonstrate that germ cell elimination in the respective mutants arises as a result of defective de novo genome methylation during reprogramming rather than because of a function for the respective factors within spermatogonia...
May 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29728366/the-hush-complex-cooperates-with-trim28-to-repress-young-retrotransposons-and-new-genes
#11
Luisa Robbez-Masson, Christopher H C Tie, Lucia Conde, Hale Tunbak, Connor Husovsky, Iva A Tchasovnikarova, Richard T Timms, Javier Herrero, Paul J Lehner, Helen M Rowe
Retrotransposons encompass half of the human genome and contribute to the formation of heterochromatin, which provides nuclear structure and regulates gene expression. Here, we asked if the human silencing hub (HUSH) complex is necessary to silence retrotransposons and whether it collaborates with TRIM28 and the chromatin remodeler ATRX at specific genomic loci. We show that the HUSH complex contributes to de novo repression and DNA methylation of a SVA retrotransposon reporter. By using naïve vs. primed mouse pluripotent stem cells, we reveal a critical role for the HUSH complex in naïve cells, implicating it in programming epigenetic marks in development...
May 4, 2018: Genome Research
https://www.readbyqxmd.com/read/29716624/reconstruction-of-a-replication-competent-ancestral-murine-endogenous-retrovirus-l
#12
Daniel Blanco-Melo, Robert J Gifford, Paul D Bieniasz
BACKGROUND: About 10% of the mouse genome is composed of endogenous retroviruses (ERVs) that represent a molecular fossil record of past retroviral infections. One such retrovirus, murine ERV-L (MuERV-L) is an env-deficient ERV that has undergone episodic proliferation, with the most recent amplification occurring ~ 2 million years ago. MuERV-L related sequences have been co-opted by mice for antiretroviral defense, and possibly as promoters for some genes that regulate totipotency in early mouse embryos...
May 2, 2018: Retrovirology
https://www.readbyqxmd.com/read/29706951/transcriptional-modulation-of-human-endogenous-retroviruses-in-primary-cd4-t-cells-following-vorinostat-treatment
#13
Cory H White, Nadejda Beliakova-Bethell, Steven M Lada, Michael S Breen, Tara P Hurst, Celsa A Spina, Douglas D Richman, John Frater, Gkikas Magiorkinis, Christopher H Woelk
The greatest obstacle to a cure for HIV is the provirus that integrates into the genome of the infected cell and persists despite antiretroviral therapy. A "shock and kill" approach has been proposed as a strategy for an HIV cure whereby drugs and compounds referred to as latency-reversing agents (LRAs) are used to "shock" the silent provirus into active replication to permit "killing" by virus-induced pathology or immune recognition. The LRA most utilized to date in clinical trials has been the histone deacetylase (HDAC) inhibitor-vorinostat...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29703894/a-somatic-role-for-the-histone-methyltransferase-setdb1-in-endogenous-retrovirus-silencing
#14
Masaki Kato, Keiko Takemoto, Yoichi Shinkai
Subsets of endogenous retroviruses (ERVs) are derepressed in mouse embryonic stem cells (mESCs) deficient for Setdb1, which catalyzes histone H3 lysine 9 trimethylation (H3K9me3). Most of those ERVs, including IAPs, remain silent if Setdb1 is deleted in differentiated embryonic cells; however they are derepressed when deficient for Dnmt1, suggesting that Setdb1 is dispensable for ERV silencing in somatic cells. However, H3K9me3 enrichment on ERVs is maintained in differentiated cells and is mostly diminished in mouse embryonic fibroblasts (MEFs) lacking Setdb1...
April 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29669918/horizontal-transfer-of-retrotransposons-between-bivalves-and-other-aquatic-species-of-multiple-phyla
#15
Michael J Metzger, Ashley N Paynter, Mark E Siddall, Stephen P Goff
The LTR retrotransposon Steamer is a selfish endogenous element in the soft-shell clam genome that was first detected because of its dramatic amplification in bivalve transmissible neoplasia afflicting the species. We amplified and sequenced related retrotransposons from the genomic DNA of many other bivalve species, finding evidence of horizontal transfer of retrotransposons from the genome of one species to another. First, the phylogenetic tree of the Steamer -like elements from 19 bivalve species is markedly discordant with host phylogeny, suggesting frequent cross-species transfer throughout bivalve evolution...
April 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29656370/role-of-exosomes-in-human-retroviral-mediated-disorders
#16
REVIEW
Monique Anderson, Fatah Kashanchi, Steven Jacobson
Retroviruses comprise an ancient and varied group of viruses with the unique ability to integrate DNA from an RNA transcript into the genome, a subset of which are able to integrate in humans. The timing of these integrations during human history has dictated whether these viruses have remained exogenous and given rise to various human diseases or have become inseparable from the host genome (endogenous retroviruses). Given the ability of retroviruses to integrate into the host and subsequently co-opt host cellular process for viral propagation, retroviruses have been shown to be closely associated with several cellular processes including exosome formation...
April 14, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29642581/remnants-of-an-ancient-deltaretrovirus-in-the-genomes-of-horseshoe-bats-rhinolophidae
#17
Tomáš Hron, Helena Farkašová, Robert J Gifford, Petr Benda, Pavel Hulva, Tamás Görföl, Jan Pačes, Daniel Elleder
Endogenous retrovirus (ERV) sequences provide a rich source of information about the long-term interactions between retroviruses and their hosts. However, most ERVs are derived from a subset of retrovirus groups, while ERVs derived from certain other groups remain extremely rare. In particular, only a single ERV sequence has been identified that shows evidence of being related to an ancient Deltaretrovirus , despite the large number of vertebrate genome sequences now available. In this report, we identify a second example of an ERV sequence putatively derived from a past deltaretroviral infection, in the genomes of several species of horseshoe bats (Rhinolophidae)...
April 10, 2018: Viruses
https://www.readbyqxmd.com/read/29642384/tracking-the-continuous-evolutionary-processes-of-an-endogenous-retrovirus-of-the-domestic-cat-erv-dc
#18
REVIEW
Junna Kawasaki, Kazuo Nishigaki
An endogenous retrovirus (ERV) is a remnant of an ancient retroviral infection in the host genome. Although most ERVs have lost their viral productivity, a few ERVs retain their replication capacity. In addition, partially inactivated ERVs can present a potential risk to the host via their encoded virulence factors or the generation of novel viruses by viral recombination. ERVs can also eventually acquire a biological function, and this ability has been a driving force of host evolution. Therefore, the presence of an ERV can be harmful or beneficial to the host...
April 6, 2018: Viruses
https://www.readbyqxmd.com/read/29626931/who-needs-this-junk-or-genomic-dark-matter
#19
REVIEW
O I Podgornaya, D I Ostromyshenskii, N I Enukashvily
Centromeres (CEN), pericentromeric regions (periCEN), and subtelomeric regions (subTel) comprise the areas of constitutive heterochromatin (HChr). Tandem repeats (TRs or satellite DNA) are the main components of HChr forming no less than 10% of the mouse and human genome. HChr is assembled within distinct structures in the interphase nuclei of many species - chromocenters. In this review, the main classes of HChr repeat sequences are considered in the order of their number increase in the sequencing reads of the mouse chromocenters (ChrmC)...
April 2018: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29624743/absence-of-interaction-between-porcine-endogenous-retrovirus-and-porcine-cytomegalovirus-in-pig-to-baboon-renal-xenotransplantation-in-vivo
#20
Jay A Fishman, David H Sachs, Kazuhiko Yamada, Robert A Wilkinson
BACKGROUND: Studies of xenotransplantation from swine have identified porcine viruses as potential barriers to clinical trials. The biology of these viruses has not been extensively investigated in the in vivo xeno-environment. Enhancement of viral gene expression by viral and cellular factors acting in trans has been demonstrated for certain viruses, including bidirectional interactions between human herpesviruses and endogenous (HERV) and exogenous (HIV) retroviruses. Both porcine cytomegalovirus (PCMV) and porcine endogenous retrovirus (PERV) infections have been identified in xenografts from swine...
April 6, 2018: Xenotransplantation
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