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Activation induced cytidine deaminase

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https://read.qxmd.com/read/30701532/hiv-1-tat-protein-induces-aberrant-activation-of-aicda-in-human-b-lymphocytes-from-peripheral-blood
#1
Fatimata Bintou Sall, Rawan El Amine, Diana Markozashvili, Tatyana Tsfasman, Eric Oksenhendler, Marc Lipinski, Yegor Vassetzky, Diego Germini
Individuals infected with human immunodeficiency virus (HIV) are at increased risk for Burkitt lymphoma, a B-cell malignancy which occurs after a chromosomal translocation rearranging the MYC oncogene with an immunoglobulin gene locus, usually the IGH heavy chain gene locus. We have previously reported that the HIV protein Tat which circulates in all HIV-positive individuals whatever their immune status caused an increased rate of colocalization between IGH and MYC in B-cells nuclei. We here present in vitro evidence that Tat activates the expression of the AICDA gene that encodes the activation-induced cytidine deaminase whose physiological function is to create double-strand breaks for immunoglobulin gene maturation...
January 31, 2019: Journal of Cellular Physiology
https://read.qxmd.com/read/30679751/up-regulation-of-activation-induced-cytidine-deaminase-and-its-strong-expression-in-extra-germinal-centres-in-igg4-related-disease
#2
Yuka Gion, Mai Takeuchi, Rei Shibata, Katsuyoshi Takata, Tomoko Miyata-Takata, Yorihisa Orita, Tomoyasu Tachibana, Tadashi Yoshino, Yasuharu Sato
Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic disorder involving benign mass formation due to fibrosis and intense lymphoplasmacytosis; the chronic inflammation associated with the disease might also contribute to oncogenesis. Activation-induced cytidine deaminase (AID), normally expressed in germinal centre activated B-cells, is an enzyme that edits DNA/RNA and induces somatic hypermutation and Ig class switching. AID expression is strictly controlled under physiological conditions; however, chronic inflammation and some infectious agents induce its up-regulation...
January 24, 2019: Scientific Reports
https://read.qxmd.com/read/30679716/elephant-apobec3a-cytidine-deaminase-induces-massive-double-stranded-dna-breaks-and-apoptosis
#3
Xiongxiong Li, Vincent Caval, Simon Wain-Hobson, Jean-Pierre Vartanian
The incidence of developing cancer should increase with the body mass, yet is not the case, a conundrum referred to as Peto's paradox. Elephants have a lower incidence of cancer suggesting that these animals have probably evolved different ways to protect themselves against the disease. The paradox is worth revisiting with the realization that most mammals encode an endogenous APOBEC3 cytidine deaminase capable of mutating single stranded DNA. Indeed, the mutagenic activity of some APOBEC3 enzymes has been shown to introduce somatic mutations into genomic DNA...
January 24, 2019: Scientific Reports
https://read.qxmd.com/read/30648968/reprogramming-the-antigen-specificity-of-b-cells-using-genome-editing-technologies
#4
James E Voss, Alicia Gonzalez-Martin, Raiees Andrabi, Roberta P Fuller, Ben Murrell, Laura E McCoy, Katelyn Porter, Deli Huang, Wenjuan Li, Devin Sok, Khoa Le, Bryan Briney, Morgan Chateau, Geoffrey Rogers, Lars Hangartner, Ann J Feeney, David Nemazee, Paula Cannon, Dennis R Burton
We have developed a method to introduce novel paratopes into the human antibody repertoire by modifying the immunoglobulin (Ig) genes of mature B cells directly using genome editing technologies. We used CRISPR-Cas9 in a homology directed repair strategy, to replace the heavy chain (HC) variable region in B cell lines with that from an HIV broadly neutralizing antibody (bnAb), PG9. Our strategy is designed to function in cells that have undergone VDJ recombination using any combination of variable (V), diversity (D) and joining (J) genes...
January 17, 2019: ELife
https://read.qxmd.com/read/30621148/kdelr2-competes-with-measles-virus-envelope-proteins-for-cellular-chaperones-reducing-their-chaperone-mediated-cell-surface-transport
#5
Vishakha Tiwarekar, Markus Fehrholz, Jürgen Schneider-Schaulies
Recently, we found that the cytidine deaminase APOBEC3G (A3G) inhibits measles (MV) replication. Using a microarray, we identified differential regulation of several host genes upon ectopic expression of A3G. One of the up-regulated genes, the endoplasmic reticulum (ER) protein retention receptor KDELR2, reduced MV replication ~5 fold when it was over-expressed individually in Vero and CEM-SS T cells. Silencing of KDELR2 in A3G-expressing Vero cells abrogated the antiviral activity induced by A3G, confirming its role as an A3G-regulated antiviral host factor...
January 4, 2019: Viruses
https://read.qxmd.com/read/30573564/safety-and-efficacy-of-an-oncolytic-viral-strategy-using-bortezomib-with-ice-r-in-relapsed-refractory-hiv-positive-lymphomas
#6
Erin G Reid, David Looney, Frank Maldarelli, Ariela Noy, David Henry, David Aboulafia, Juan Carlos Ramos, Joseph Sparano, Richard F Ambinder, Jeannette Lee, Ethel Cesarman, Sara Yahyaei, Ronald Mitsuyasu, William Wachsman
HIV-associated lymphomas (HALs) have high rates of latent infection by gammaherpesviruses (GHVs). We hypothesized that proteasome inhibition would induce lytic activation of GHVs and inhibit HIV infectivity via preservation of cytidine deaminase APOBEC3G, improving lymphoma control. We tested this oncolytic and antiviral strategy by using bortezomib combined with ifosfamide, carboplatin, and etoposide (ICE) alone or with rituximab (ICE/R) in relapsed/refractory HAL. A 3+3 dose-escalation design was used with a 7-day lead-in period of single-agent bortezomib...
December 26, 2018: Blood Advances
https://read.qxmd.com/read/30535046/cytidine-deaminase-enables-toll-like-receptor-8-activation-by-cytidine-or-its-analogs
#7
Katsuhiro Furusho, Takuma Shibata, Ryota Sato, Ryutaro Fukui, Yuji Motoi, Yun Zhang, Shin-Ichiroh Saitoh, Takeshi Ichinohe, Masafumi Moriyama, Seiji Nakamura, Kensuke Miyake
Toll-like receptor 8 (TLR8), a sensor for pathogen-derived single-stranded RNA (ssRNA), binds to uridine (Uri) and ssRNA to induce defense responses. We here show that cytidine (Cyd) with ssRNA also activated TLR8 in peripheral blood leukocytes (PBLs) and a myeloid cell line U937, but not in an embryonic kidney cell line 293T. Cyd deaminase (CDA), an enzyme highly expressed in leukocytes, deaminates Cyd to Uri. CDA expression enabled TLR8 response to Cyd and ssRNA in 293T cells. CDA deficiency and a CDA inhibitor both reduced TLR8 responses to Cyd and ssRNA in U937...
December 10, 2018: International Immunology
https://read.qxmd.com/read/30530594/the-mtorc1-4e-bp-eif4e-axis-promotes-antibody-class-switching-in-b-lymphocytes
#8
Honyin Chiu, Leandra V Jackson, Kwon Ik Oh, Annie Mai, Ze'ev A Ronai, Davide Ruggero, David A Fruman
During an adaptive immune response, activated mature B cells give rise to Ab-secreting plasma cells to fight infection. B cells undergo Ab class switching to produce different classes of Abs with varying effector functions. The mammalian/mechanistic target of rapamycin (mTOR) signaling pathway is activated during this process, and disrupting mTOR complex 1 (mTORC1) in B cells impairs class switching by a poorly understood mechanism. In particular, it is unclear which mTORC1 downstream substrates control this process...
December 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30515165/dysregulated-mir-155-and-mir-125b-are-related-to-impaired-b-cell-responses-in-down-syndrome
#9
Chiara Farroni, Emiliano Marasco, Valentina Marcellini, Ezio Giorda, Diletta Valentini, Stefania Petrini, Valentina D'Oria, Marco Pezzullo, Simona Cascioli, Marco Scarsella, Alberto G Ugazio, Giovanni C De Vincentiis, Ola Grimsholm, Rita Carsetti
Children with Down Syndrome (DS) suffer from immune deficiency with a severe reduction in switched memory B cells (MBCs) and poor response to vaccination. Chromosome 21 (HSA21) encodes two microRNAs (miRs), miR-125b, and miR-155, that regulate B-cell responses. We studied B- and T- cell subpopulations in tonsils of DS and age-matched healthy donors (HD) and found that the germinal center (GC) reaction was impaired in DS. GC size, numbers of GC B cells and Follicular Helper T cells (TFH ) expressing BCL6 cells were severely reduced...
2018: Frontiers in Immunology
https://read.qxmd.com/read/30456840/recent-progress-in-follicular-lymphoma-in-japan-and-characteristics-of-the-duodenal-type
#10
REVIEW
Tadashi Yoshino, Katsuyoshi Takata, Takehiro Tanaka, Yasuharu Sato, Akira Tari, Hiroyuki Okada
The incidence of lymphoma has rapidly increased over the last 40 years in Japan, following a trend that is very similar to that of breast cancer. In particular, the relative frequency of follicular lymphoma (FL) has reached that in Western countries. Given its indolence, a "watch-and-wait" approach is often applied to FL patients. We have shown that FL is often detected in the second portion of the duodenum and has a distinct follicular dendritic cell distribution and heavy chain variable usage similar to mucosa-associated lymphoid tissue (MALT) lymphoma...
November 20, 2018: Pathology International
https://read.qxmd.com/read/30452740/exposure-to-1-2-dichloropropane-upregulates-the-expression-of-activation-induced-cytidine-deaminase-aid-in-human-cholangiocytes-co-cultured-with-macrophages
#11
Cai Zong, Yusuke Kimura, Kazuo Kinoshita, Shigetada Takasu, Xiao Zhang, Toshihiro Sakurai, Yoshitaka Sekido, Sahoko Ichihara, Ginji Endo, Gaku Ichihara
Background: 1,2-dichloropropane (1,2-DCP) was reclassified recently by IARC as a Group 1 carcinogen based on epidemiological studies on an outbreak of cholangiocarcinoma in offset-printing workers exposed to 1,2-DCP in Japan. However, the underlying mechanism of 1,2-DCP-induced cholangiocarcinoma remains obscure. A previous whole-genome mutation analysis of cholangiocarcinoma of four cases exposed to 1,2-DCP suggested the involvement of activation-induced cytidine deaminase (AID), based on specific signatures of mutation patterns...
November 19, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://read.qxmd.com/read/30448640/polymorphisms-of-the-cytidine-deaminase-apobec3f-have-different-hiv-1-restriction-efficiencies
#12
Nazanin Mohammadzadeh, Tyson B Follack, Robin P Love, Kris Stewart, Stephen Sanche, Linda Chelico
The APOBEC3 enzyme family are host restriction factors that induce mutagenesis of HIV-1 proviral genomes through the deamination of cytosine to form uracil in nascent single-stranded (-)DNA. HIV-1 suppresses APOBEC3 activity through the HIV-1 protein Vif that induces APOBEC3 degradation. Here we compared two common polymorphisms of APOBEC3F. We found that although both polymorphisms have HIV-1 restriction activity, APOBEC3F 108 A/231V can restrict HIV-1 ΔVif up to 4-fold more than APOBEC3F 108 S/231I and is partially protected from Vif-mediated degradation...
November 15, 2018: Virology
https://read.qxmd.com/read/30368590/activation-induced-deaminase-and-its-splice-variants-associate-with-trisomy-12-in-chronic-lymphocytic-leukemia
#13
Kristina Zaprazna, Kamila Reblova, Veronika Svobodova, Lenka Radova, Vojtech Bystry, Jiri Baloun, Kristina Durechova, Nikola Tom, Tomas Loja, Martina Buresova, Kamila Stranska, Alexandra Oltova, Michael Doubek, Michael L Atchison, Martin Trbusek, Jitka Malcikova, Sarka Pospisilova
Activation-induced cytidine deaminase (AID) is a mutator enzyme essential for somatic hypermutation (SHM) and class switch recombination (CSR) during effective adaptive immune responses. Its aberrant expression and activity have been detected in lymphomas, leukemias, and solid tumors. In chronic lymphocytic leukemia (CLL) increased expression of alternatively spliced AID variants has been documented. We used real-time RT-PCR to quantify the expression of AID and its alternatively spliced transcripts (AIDΔE4a, AIDΔE4, AIDivs3, and AIDΔE3E4) in 149 CLL patients and correlated this expression to prognostic markers including recurrent chromosomal aberrations, the presence of complex karyotype, mutation status of the immunoglobulin heavy chain variable gene, and recurrent mutations...
October 27, 2018: Annals of Hematology
https://read.qxmd.com/read/30357811/aid-and-tet2-co-operation-modulates-fanca-expression-by-active-demethylation-in-diffuse-large-b-cell-lymphoma
#14
J Jiao, Y Jin, M Zheng, H Zhang, M Yuan, Z Lv, W Odhiambo, X Yu, P Zhang, C Li, Y Ma, Y Ji
Diffuse large B cell lymphoma (DLBCL) is traced to a mature B malignance carrying abnormal activation-induced cytidine deaminase (AID) expression. AID activity initially focuses on deamination of cytidine to uracil to generate somatic hypermutation and class-switch recombination of the immunoglobulin (Ig), but recently it has been implicated in DNA demethylation of genes required for B cell development and proliferation in the germinal centre (GC). However, whether AID activity on mutation or demethylation of genes involves oncogenesis of DLBCL has not been well characterized...
October 25, 2018: Clinical and Experimental Immunology
https://read.qxmd.com/read/30348658/pillars-article-class-switch-recombination-and-hypermutation-require-activation-induced-cytidine-deaminase-aid-a-potential-rna-editing-enzyme-cell-2000-102-553-563
#15
Masamichi Muramatsu, Kazuo Kinoshita, Sidonia Fagarasan, Shuichi Yamada, Yoichi Shinkai, Tasuku Honjo
No abstract text is available yet for this article.
November 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30341187/traf2-deficiency-in-b-cells-impairs-cd40-induced-isotype-switching-that-can-be-rescued-by-restoring-nf-%C3%AE%C2%BAb1-activation
#16
Rachel A Woolaver, Xiaoguang Wang, Yonatan Dollin, Ping Xie, Jing H Wang, Zhangguo Chen
Effective humoral immunity requires class switch recombination (CSR) catalyzed by activation-induced cytidine deaminase (AID). In response to T cell-dependent (TD) Ags, CSR can be induced by CD40 signaling in B cells. TNFR-associated factors 2 and 3 (TRAF2/TRAF3) function as adaptors of the CD40 signaling pathway. B cell-intrinsic TRAF2 or TRAF3 (B-TRAF2 or B-TRAF3) knockout mice were previously reported to have indistinguishable phenotypes in gene expression, B cell survival and development, and enlarged peripheral lymphoid organs...
December 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30333176/dynamics-of-virus-specific-memory-b-cells-and-plasmablasts-following-cns-viral-infection
#17
Jeffrey R Atkinson, Mihyun Hwang, Angel Reyes-Rodriguez, Cornelia C Bergmann
Humoral responses within the central nervous system (CNS) are common to many neurotropic viral infections, with antibody (Ab) secreting cells (ASC) contributing to local protection. However, a role for virus-specific memory B cells (Bmem) within the CNS is poorly explored due to lack of robust phenotypic or functional identification in mice. This study takes advantage of mice expressing tamoxifen-inducible Cre recombinase (Cre-ERT2) under the Aicda promoter crossed with Rosa26-loxP-tdTomato reporter mice (AIDCre -Rosa26tdTomato ) to monitor B cells having undergone activation-induced cytidine deaminase (AID)-mediated somatic hypermutation (SHM) following neurotropic coronavirus infection...
October 17, 2018: Journal of Virology
https://read.qxmd.com/read/30333118/the-egfr-t790m-mutation-is-acquired-through-aicda-mediated-deamination-of-5-methylcytosine-following-tki-treatment-in-lung-cancer
#18
Najwa El Kadi, Luo Wang, April Davis, Hasan Korkaya, Alexander Cooke, Varun Vadnala, Noah A Brown, Bryan L Betz, Marilia Cascalho, Gregory P Kalemkerian, Khaled A Hassan
Almost all patients with EGFR-driven lung cancer who are treated with EGFR tyrosine kinase inhibitors (TKI) develop resistance to treatment. A single base (c.2369C>T) transition mutation, EGFR T790M, is the most frequent resistance event after first-generation exposure to EGFR TKIs. Whether T790M mutation is acquired or is selected from a preexisting clone has been a matter of significant debate. In this study, we show that treatment with EGFR TKIs leads to activation of the NFκB pathway, which in turn induces expression of activation-induced cytidine deaminase (AICDA)...
October 17, 2018: Cancer Research
https://read.qxmd.com/read/30293785/the-chromatin-reader-zmynd8-regulates-igh-enhancers-to-promote-immunoglobulin-class-switch-recombination
#19
Verónica Delgado-Benito, Daniel B Rosen, Qiao Wang, Anna Gazumyan, Joy A Pai, Thiago Y Oliveira, Devakumar Sundaravinayagam, Wenzhu Zhang, Matteo Andreani, Lisa Keller, Kyong-Rim Kieffer-Kwon, Aleksandra Pękowska, Seolkyoung Jung, Madlen Driesner, Roman I Subbotin, Rafael Casellas, Brian T Chait, Michel C Nussenzweig, Michela Di Virgilio
Class switch recombination (CSR) is a DNA recombination reaction that diversifies the effector component of antibody responses. CSR is initiated by activation-induced cytidine deaminase (AID), which targets transcriptionally active immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3' Igh super-enhancer, 3' regulatory region (3'RR), is essential for acceptor region transcription, but how this function is regulated is unknown. Here, we identify the chromatin reader ZMYND8 as an essential regulator of the 3'RR...
November 15, 2018: Molecular Cell
https://read.qxmd.com/read/30293782/genetic-modulation-of-rna-splicing-with-a-crispr-guided-cytidine-deaminase
#20
Juanjuan Yuan, Yunqing Ma, Tao Huang, Yanhao Chen, Yuanzheng Peng, Bing Li, Jia Li, Yuchen Zhang, Bing Song, Xiaofang Sun, Qiurong Ding, Yan Song, Xing Chang
RNA splicing is a critical mechanism by which to modify transcriptome, and its dysregulation is the underlying cause of many human diseases. It remains challenging, however, to genetically modulate a splicing event in its native context. Here, we demonstrate that a CRISPR-guided cytidine deaminase (i.e., targeted-AID mediated mutagenesis [TAM]) can efficiently modulate various forms of mRNA splicing. By converting invariant guanines to adenines at either 5' or 3' splice sites (SS), TAM induces exon skipping, activation of alternative SS, switching between mutually exclusive exons, or targeted intron retention...
October 18, 2018: Molecular Cell
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