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https://www.readbyqxmd.com/read/29345375/understanding-the-regulation-of-apobec3-expression-current-evidence-and-much-to-learn
#1
REVIEW
Daniela Angela Covino, Maria Cristina Gauzzi, Laura Fantuzzi
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytosine deaminases plays crucial roles in innate immunity through the ability of restricting viral replication by deamination and mutation of viral genomes. The antiviral function of these proteins was first discovered when research in the field of HIV infection revealed that one member of the family, namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral infectivity factor protein drives the proteosomal degradation of this enzyme, thus overriding its antiviral function...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29343743/expression-and-subcellular-localisation-of-aid-and-apobec3-in-adenoid-and-palatine-tonsils
#2
Noriko Seishima, Satoru Kondo, Kousho Wakae, Naohiro Wakisaka, Eiji Kobayashi, Makoto Kano, Makiko Moriyama-Kita, Yosuke Nakanishi, Kazuhira Endo, Tomoko Imoto, Kazuya Ishikawa, Hisashi Sugimoto, Miyako Hatano, Takayoshi Ueno, Miki Koura, Koichi Kitamura, Masamichi Muramatsu, Tomokazu Yoshizaki
Activation-induced cytidine deaminase (AID) and apolipoprotein B mRNA-editing catalytic polypeptide 3 (A3) family are cytidine deaminases that play critical roles in B-cell maturation, antiviral immunity and carcinogenesis. Adenoids and palatine tonsils are secondary lymphoid immune organs, in which AID and A3s are thought to have several physiological or pathological roles. However, the expression of AID or A3s in these organs has not been investigated. Therefore, we investigated the expression profiles of AID and A3s, using 67 samples of adenoids and palatine tonsils from patients, with reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analyses...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29324878/the-curious-case-of-apobec3-activation-by-cancer-associated-human-papillomaviruses
#3
Nicholas A Wallace, Karl Münger
No abstract text is available yet for this article.
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29323274/apobec3-induces-mutations-during-repair-of-crispr-cas9-generated-dna-breaks
#4
Liqun Lei, Hongquan Chen, Wei Xue, Bei Yang, Bian Hu, Jia Wei, Lijie Wang, Yiqiang Cui, Wei Li, Jianying Wang, Lei Yan, Wanjing Shang, Jimin Gao, Jiahao Sha, Min Zhuang, Xingxu Huang, Bin Shen, Li Yang, Jia Chen
The APOBEC-AID family of cytidine deaminase prefers single-stranded nucleic acids for cytidine-to-uridine deamination. Single-stranded nucleic acids are commonly involved in the DNA repair system for breaks generated by CRISPR-Cas9. Here, we show in human cells that APOBEC3 can trigger cytidine deamination of single-stranded oligodeoxynucleotides, which ultimately results in base substitution mutations in genomic DNA through homology-directed repair (HDR) of Cas9-generated double-strand breaks. In addition, the APOBEC3-catalyzed deamination in genomic single-stranded DNA formed during the repair of Cas9 nickase-generated single-strand breaks in human cells can be further processed to yield mutations mainly involving insertions or deletions (indels)...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29304101/fab-based-inhibitors-reveal-ubiquitin-independent-functions-for-hiv-vif-neutralization-of-apobec3-restriction-factors
#5
Jennifer M Binning, Amber M Smith, Judd F Hultquist, Charles S Craik, Nathalie Caretta, Melody G Campbell, Lily Burton, Florencia La Greca, Michael J McGregor, Hai M Ta, Koen Bartholomeeusen, B Matija Peterlin, Nevan J Krogan, Natalia Sevillano, Yifan Cheng, John D Gross
The lentiviral protein Viral Infectivity Factor (Vif) counteracts the antiviral effects of host APOBEC3 (A3) proteins and contributes to persistent HIV infection. Vif targets A3 restriction factors for ubiquitination and proteasomal degradation by recruiting them to a multi-protein ubiquitin E3 ligase complex. Here, we describe a degradation-independent mechanism of Vif-mediated antagonism that was revealed through detailed structure-function studies of antibody antigen-binding fragments (Fabs) to the Vif complex...
January 5, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29298890/full-length-glycosylated-gag-of-murine-leukemia-virus-can-associate-with-the-viral-envelope-as-a-type-i-integral-membrane-protein
#6
Tyler Milston Renner, Kasandra Bélanger, Cindy Lam, Maria Rosales Gerpe, Joanne Eileen McBane, Marc-André Langlois
The glycosylated Gag protein (gPr80) of murine leukemia viruses (MLVs) has been shown to exhibit multiple roles in facilitating retrovirus release, infection and resistance to host-encoded retroviral restriction factors such as APOBEC3, SERINC3 and SERINC5. One way gPr80 helps MLVs escape host innate immune restriction is by increasing capsid stability, a feature that protects viral replication intermediates from being detected by cytosolic DNA sensors. gPr80 also increases the resistance of MLVs against deamination and restriction by mouse APOBEC3 (mA3)...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29211501/viral-subversion-of-apobec3s-lessons-for-anti-tumor-immunity-and-tumor-immunotherapy
#7
Faezeh Borzooee, Mahdi Asgharpour, Emma Quinlan, Michael D Grant, Mani Larijani
APOBEC3s (A3) are endogenous DNA-editing enzymes that are expressed in immune cells including T lymphocytes. A3s target and mutate the genomes of retroviruses that infect immune tissues such as the human immunodeficiency virus (HIV). Therefore, A3s were classically defined as host anti-viral innate immune factors. In contrast, we and others showed that A3s can also benefit the virus by mediating escape from adaptive immune recognition and drugs. Crucially, whether A3-mediated mutations help or hinder HIV, is not up to chance...
December 6, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/29166639/apobec3a-expression-in-penile-squamous-cell-carcinoma
#8
Martina Heller, Elena-Sophie Prigge, Adam Kaczorowski, Magnus von Knebel Doeberitz, Markus Hohenfellner, Stefan Duensing
BACKGROUND: APOBECs (apolipoprotein B mRNA-editing catalytic polypeptides) are cytidine deaminases that have been implicated in the host defense against viruses by blocking viral replication. They have also been shown to play a role in genome hypermutation in several human cancers. An APOBEC3 hypermutation signature has been discovered in cervical cancer, which is intimately associated with infection by high-risk human papillomaviruses (HPVs). At the same time, HPV genomes themselves are subject to DNA editing by APOBECs...
November 23, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29153851/apobec-enzymes-as-targets-for-virus-and-cancer-therapy
#9
REVIEW
Margaret E Olson, Reuben S Harris, Daniel A Harki
Human DNA cytosine-to-uracil deaminases catalyze mutations in both pathogen and cellular genomes. APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H restrict human immunodeficiency virus 1 (HIV-1) infection in cells deficient in the viral infectivity factor (Vif), and have the potential to catalyze sublethal levels of mutation in viral genomes in Vif-proficient cells. At least two APOBEC3 enzymes, and in particular APOBEC3B, are sources of somatic mutagenesis in cancer cells that drive tumor evolution and may manifest clinically as recurrence, metastasis, and/or therapy resistance...
November 14, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29149056/characterization-of-ovine-a3z1-restriction-properties-against-small-ruminant-lentiviruses-srlvs
#10
Lorena de Pablo-Maiso, Idoia Glaria, Helena Crespo, Estanislao Nistal-Villán, Valgerdur Andrésdóttir, Damián de Andrés, Beatriz Amorena, Ramsés Reina
Intrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible to small ruminant lentivirus (SRLVs) infection and contain three APOBEC3 genes encoding four proteins (A3Z1, Z2, Z3 and Z2-Z3) with yet not deeply described antiviral properties...
November 17, 2017: Viruses
https://www.readbyqxmd.com/read/29100527/hpv11-e6-mutation-by-overexpression-of-apobec3a-and-effects-of-interferon-%C3%AF-on-apobec3s-and-hpv11-e6-expression-in-hpv11-hacat-cells
#11
Yongfang Wang, Xinyu Li, Shasha Song, Yang Sun, Jiafen Zhang, Changming Yu, Wei Chen
BACKGROUND: Condyloma acuminatum, infected by low-risk human papillomaviruses (e.g., HPV6 and HPV11), is one of the most widespread sexually transmitted diseases. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 proteins (APOBEC3s, A3s) are cellular cytidine deaminases acting as antiviral factors through hypermutation of viral genome. However, it remains unknown whether A3s results in HPV11 gene mutations and interferon-ω (IFN-ω) exhibits antiviral activities through the A3s system...
November 3, 2017: Virology Journal
https://www.readbyqxmd.com/read/29100317/the-30-kb-deletion-in-the-apobec3-cluster-decreases-apobec3a-and-apobec3b-expression-and-creates-a-transcriptionally-active-hybrid-gene-but-does-not-associate-with-breast-cancer-in-the-european-population
#12
Katarzyna Klonowska, Wojciech Kluzniak, Bogna Rusak, Anna Jakubowska, Magdalena Ratajska, Natalia Krawczynska, Danuta Vasilevska, Karol Czubak, Marzena Wojciechowska, Cezary Cybulski, Jan Lubinski, Piotr Kozlowski
APOBEC3B, in addition to other members of the APOBEC3 gene family, has recently been intensively studied due to its identification as a gene whose activation in cancer is responsible for a specific pattern of massively occurring somatic mutations. It was recently shown that a common large deletion in the APOBEC3 cluster (the APOBEC3B deletion) may increase the risk of breast cancer. However, conflicting evidence regarding this association was also reported. In the first step of our study, using different approaches, including an in-house designed multiplex ligation-dependent probe amplification assay, we analyzed the structure of the deletion and showed that although the breakpoints are located in highly homologous regions, which may generate recurrent occurrence of similar but not identical deletions, there is no sign of deletion heterogeneity...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29064351/mechanisms-and-factors-that-drive-extensive-human-immunodeficiency-virus-type-1-hypervariability-an-overview
#13
Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Mohammad Ali Alqudah, Mohammad Mahmoud Yaseen
The extensive hypervariability of human immunodeficiency virus type-1 (HIV-1) populations represents a major barrier against the success of currently available antiretroviral therapy. Moreover, it is still the most important obstacle that faces the development of an effective preventive vaccine against this infectious virus. Indeed, several factors can drive such hypervariability within and between HIV-1 patients. These factors include: first, the very low fidelity nature of HIV-1 reverse transcriptase; second, the extremely high HIV-1 replication rate; and third, the high genomic recombination rate that the virus has...
October 24, 2017: Viral Immunology
https://www.readbyqxmd.com/read/29057505/ductal-cells-of-minor-salivary-glands-in-sj%C3%A3-gren-s-syndrome-patients-express-line-1-orf2p-and-apobec3b
#14
Eleni-Marina Kalogirou, Evangelia P Piperi, Konstantinos I Tosios, Evangelos Tsiambas, Galinos Fanourakis, Alexandra Sklavounou
BACKGROUND: Type I interferon activation is a hallmark event in Sjögren's syndrome. L1 retroelements stimulate plasmacytoid dendritic cells, activating the type I interferons, and are regulated by various mechanisms, including the APOBEC3 deaminases. As L1s are potential trigger factors in autoimmunity, we aimed to investigate the immunohistochemical localization of L1 ORF2 and its inhibitor APOBEC3B protein in minor salivary glands of Sjögren's syndrome patients. METHODS: Twenty minor salivary gland-tissue samples from 20 Sjögren's syndrome patients, classified according to Tarpley's histological criteria, and 10 controls were evaluated for L1 ORF2p and APOBEC3B expression via immunohistochemistry...
October 23, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29044109/apobec3h-structure-reveals-an-unusual-mechanism-of-interaction-with-duplex-rna
#15
Jennifer A Bohn, Keyur Thummar, Ashley York, Alice Raymond, W Clay Brown, Paul D Bieniasz, Theodora Hatziioannou, Janet L Smith
The APOBEC3 family of cytidine deaminases cause lethal hypermutation of retroviruses via deamination of newly reverse-transcribed viral DNA. Their ability to bind RNA is essential for virion infiltration and antiviral activity, yet the mechanisms of viral RNA recognition are unknown. By screening naturally occurring, polymorphic, non-human primate APOBEC3H variants for biological and crystallization properties, we obtained a 2.24-Å crystal structure of pig-tailed macaque APOBEC3H with bound RNA. Here, we report that APOBEC3H forms a dimer around a short RNA duplex and, despite the bound RNA, has potent cytidine deaminase activity...
October 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28983111/ifn-%C3%AE-mediated-base-excision-repair-pathway-correlates-with-antiviral-response-against-hepatitis-b-virus-infection
#16
Yong Li, Yuchen Xia, Meifang Han, Guang Chen, Dake Zhang, Wolfgang E Thasler, Ulrike Protzer, Qin Ning
Previous studies identified APOBEC deaminases as enzymes targeting hepatitis B virus (HBV) DNA in the nucleus thus affecting its persistence. Interferon (IFN)-α treated chimpanzees and hepatitis C patients showed elevated APOBEC expression. We thus hypothesized that the responses to IFN-α treatment of chronic hepatitis B (CHB) patients is influenced by IFN-induced base excision repair (BER). CHB-treatment naïve patients, patients treated with PEGylated IFN-α, and patients with sequential treatment of Entecavior and PEGylated IFN-α were recruited...
October 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28981865/enzyme-cycling-contributes-to-efficient-induction-of-genome-mutagenesis-by-the-cytidine-deaminase-apobec3b
#17
Madison B Adolph, Robin P Love, Yuqing Feng, Linda Chelico
The single-stranded DNA cytidine deaminases APOBEC3B, APOBEC3H haplotype I, and APOBEC3A can contribute to cancer through deamination of cytosine to form promutagenic uracil in genomic DNA. The enzymes must access single-stranded DNA during the dynamic processes of DNA replication or transcription, but the enzymatic mechanisms enabling this activity are not known. To study this, we developed a method to purify full length APOBEC3B and characterized it in comparison to APOBEC3A and APOBEC3H on substrates relevant to cancer mutagenesis...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28963223/complete-genome-sequences-of-human-immunodeficiency-type-1-viruses-genetically-engineered-to-be-tropic-for-rhesus-macaques
#18
Masako Nomaguchi, Naoya Doi, Takaaki Koma, Akio Adachi
We have constructed two human immunodeficiency type 1 (HIV-1) derivatives, CXCR4 tropic and CCR5 tropic, that replicate in rhesus macaques. They are genetically engineered to be resistant to macaque restriction factors against HIV-1, including TRIM5α, APOBEC3, and tetherin proteins. The two HIV-1 variants described here are fundamental clones aiming for rhesus infection studies of HIV-1.
September 28, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28958921/ifna2-p-ala120thr-impairs-the-inhibitory-activity-of-interferon-%C3%AE-2-against-the-hepatitis-b-virus-through-altering-its-binding-to-the-receptor
#19
Chuming Chen, Xiang Zhu, Wenxiong Xu, Fangji Yang, Genglin Zhang, Lina Wu, Yongyuan Zheng, Zhiliang Gao, Chan Xie, Liang Peng
BACKGROUND: Our previous study found that a rare genetic mutation IFNA2p.Ala120Thr affects the structure of IFN-α2 and contributes to increased host susceptibility to CHB. However, the way in which the single amino acid residue mutation affects IFN-α2 activity is unclear. The purpose of this research was to investigate the effects and mechanisms of IFNA2p.Ala120Thr on IFN-α2 activity. METHODS: Plasmid transfection of BL-21 was used to construct both wild type IFNA2 (wt) and p...
September 25, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28900073/-molecular-mechanisms-of-hiv-1-genetic-diversity
#20
D V Sosin, N A Tchurikov
High genetic diversity of HIV-1 is the main factor behind the fact that HIV infection is widespread and difficult to treat. Although a limited number (or only one) of virus particles enters the blood upon infection, the particles are replicated in infected cells and rapidly produce new genetic variants that are resistant to the host immune system and antiretroviral drugs. This circumstance hampers the development of anti-HIV-1 vaccines and requires new antiretroviral drugs to be designed. The cause of the high variation of HIV-1 is related to the properties of its reverse transcriptase, which is error prone and often makes mistakes when transcribing virus RNA...
July 2017: Molekuliarnaia Biologiia
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