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Yusuke Matsui, Keisuke Shindo, Kayoko Nagata, Noriyoshi Yoshinaga, Kotaro Shirakawa, Masayuki Kobayashi, Akifumi Takaori-Kondo
HIV type 1 overcomes the host restriction factor apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) proteins by organizing an E3 ubiquitin ligase complex together with viral infectivity factor (Vif) and a host transcription cofactor core binding factor β (CBFβ ). CBFβ is essential for Vif to counteract APOBEC3 by enabling the recruitment of cullin 5 to the complex and increasing steady-state level of Vif protein, however, the mechanisms by which CBFβ up-regulates Vif protein remains unclear...
October 7, 2016: Journal of Biological Chemistry
Cristina J Wittkopp, Madison B Adolph, Lily I Wu, Linda Chelico, Michael Emerman
Humans express seven human APOBEC3 proteins, which can inhibit viruses and endogenous retroelements through cytidine deaminase activity. The seven paralogs differ in the potency of their antiviral effects, as well as in their antiviral targets. One APOBEC3, APOBEC3C, is exceptional as it has been found to only weakly block viruses and endogenous retroelements compared to other APOBEC3s. However, our positive selection analyses suggest that APOBEC3C has played a role in pathogen defense during primate evolution...
October 2016: PLoS Pathogens
S Kondo, K Wakae, N Wakisaka, Y Nakanishi, K Ishikawa, T Komori, M Moriyama-Kita, K Endo, S Murono, Z Wang, K Kitamura, T Nishiyama, K Yamaguchi, S Shigenobu, M Muramatsu, T Yoshizaki
The prevalence of human papillomavirus (HPV)-related oropharyngeal cancers has been increasing in developed countries. We recently demonstrated that members of the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family, which are antiviral factors, can induce hypermutation of HPV DNA in vitro. In the present study, we found numerous C-to-T and G-to-A hypermutations in the HPV16 genome in oropharyngeal cancer (OPC) biopsy samples using differential DNA denaturation PCR and next-generation sequencing...
October 3, 2016: Oncogene
(no author information available yet)
SNPs in APOBEC3 alter expression of APOBEC3A/APOBEC3B to affect somatic APOBEC-signature mutations.
September 30, 2016: Cancer Discovery
Eri Yamada, Rokusuke Yoshikawa, Yusuke Nakano, Naoko Misawa, Tomoko Kobayashi, Fengrong Ren, Taisuke Izumi, Takayuki Miyazawa, Yoshio Koyanagi, Kei Sato
Mammals have co-evolved with lentiviruses for a long time. As evidence, viral infectivity factor (Vif), encoded by lentiviruses, antagonizes the anti-viral action of cellular APOBEC3 of their hosts. Here, we address the co-evolutionary dynamics of bovine APOBEC3 and the following two bovine lentiviruses: bovine immunodeficiency virus (BIV) and Jembrana disease virus (JDV). We determined the sequences of three APOBEC3 genes of bovids belonging to the genera Bos and Bison and showed that bovine APOBEC3Z3 is under a strong positive selection...
September 26, 2016: Scientific Reports
Candace D Middlebrooks, A Rouf Banday, Konichi Matsuda, Krizia-Ivana Udquim, Olusegun O Onabajo, Ashley Paquin, Jonine D Figueroa, Bin Zhu, Stella Koutros, Michiaki Kubo, Taro Shuin, Neal D Freedman, Manolis Kogevinas, Nuria Malats, Stephen J Chanock, Montserrat Garcia-Closas, Debra T Silverman, Nathaniel Rothman, Ludmila Prokunina-Olsson
High rates of APOBEC-signature mutations are found in many tumors, but factors affecting this mutation pattern are not well understood. Here we explored the contribution of two common germline variants in the APOBEC3 region. SNP rs1014971 was associated with bladder cancer risk, increased APOBEC3B expression, and enrichment with APOBEC-signature mutations in bladder tumors. In contrast, a 30-kb deletion that eliminates APOBEC3B and creates an APOBEC3A-APOBEC3B chimera was not important in bladder cancer, whereas it was associated with breast cancer risk and enrichment with APOBEC-signature mutations in breast tumors...
September 19, 2016: Nature Genetics
Nnennaya Kanu, Maria Antonietta Cerone, Gerald Goh, Lykourgos-Panagiotis Zalmas, Jirina Bartkova, Michelle Dietzen, Nicholas McGranahan, Rebecca Rogers, Emily K Law, Irina Gromova, Maik Kschischo, Michael I Walton, Olivia W Rossanese, Jiri Bartek, Reuben S Harris, Subramanian Venkatesan, Charles Swanton
BACKGROUND: The APOBEC3 family of cytidine deaminases mutate the cancer genome in a range of cancer types. Although many studies have documented the downstream effects of APOBEC3 activity through next-generation sequencing, less is known about their upstream regulation. In this study, we sought to identify a molecular basis for APOBEC3 expression and activation. RESULTS: HER2 amplification and PTEN loss promote DNA replication stress and APOBEC3B activity in vitro and correlate with APOBEC3 mutagenesis in vivo...
2016: Genome Biology
Qinyong Gu, Zeli Zhang, Lucía Cano Ortiz, Ana Cláudia Franco, Dieter Häussinger, Carsten Münk
: Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, A3Z3 and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s...
September 14, 2016: Journal of Virology
Yali Han, Qichao Qi, Qin He, Meili Sun, Shuyun Wang, Guanzhou Zhou, Yuping Sun
Recently, a deletion in the human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) gene cluster has been associated with a modest increased risk of breast cancer, but studies yielded inconsistent results. Therefore we performed a meta-analysis to derive a more precise conclusion. Six studies including 18241 subjects were identified by searching PubMed and Embase databases from inception to April 2016. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were evaluated under allele contrast, dominant, recessive, homozygous, and heterozygous models...
September 1, 2016: Oncotarget
Sachini U Siriwardena, Kang Chen, Ashok S Bhagwat
The AID/APOBEC family enzymes convert cytosines in single-stranded DNA to uracils, causing base substitutions and strand breaks. They are induced by cytokines produced during the body's inflammatory response to infections, and they help combat infections through diverse mechanisms. AID is essential for the maturation of antibodies and causes mutations and deletions in antibody genes through somatic hypermutation (SHM) and class-switch recombination (CSR) processes. One member of the APOBEC family, APOBEC1, edits mRNA for a protein involved in lipid transport...
September 1, 2016: Chemical Reviews
Zeli Zhang, Qinyong Gu, Ananda Ayyappan Jaguva Vasudevan, Manimehalai Jeyaraj, Stanislaw Schmidt, Jörg Zielonka, Mario Perković, Jens-Ove Heckel, Klaus Cichutek, Dieter Häussinger, Sander H J Smits, Carsten Münk
: Lentiviruses have evolved the Vif protein to counteract APOBEC3 (A3) restriction factors by targeting them for proteasomal degradation. Previous studies have identified important residues in the interface of HIV-1 Vif and human APOBEC3C (hA3C) or human APOBEC3F (hA3F). However, the interaction between primate A3C proteins with HIV-1 Vif or natural HIV-1 Vif variants is still poorly understood. Here, we report that HIV-1 Vif is inactive against A3Cs of rhesus macaques (rhA3C), sooty mangabey monkeys (smmA3C) and African green monkeys, while HIV-2, SIVagm and SIVmac Vif proteins efficiently mediate the depletion of all tested A3Cs...
August 31, 2016: Journal of Virology
Ashley York, Sebla B Kutluay, Manel Errando, Paul D Bieniasz
The APOBEC3 (A3) cytidine deaminases are antiretroviral proteins, whose targets include human immunodeficiency virus type-1 (HIV-1). Their incorporation into viral particles is critical for antiviral activity and is driven by interactions with the RNA molecules that are packaged into virions. However, it is unclear whether A3 proteins preferentially target RNA molecules that are destined to be packaged and if so, how. Using cross-linking immunoprecipitation sequencing (CLIP-seq), we determined the RNA binding preferences of the A3F, A3G and A3H proteins...
August 2016: PLoS Pathogens
Jiang Gu, Qihan Chen, Xiao Xiao, Fumiaki Ito, Aaron Wolfe, Xiaojiang S Chen
APOBEC3H (A3H) is the most polymorphic member in the APOBEC3 family. Seven haplotypes (hap I-VII) and four mRNA splicing variants (SV) of A3H have been identified. The various haplotypes differ in anti-HIV activity, which is attributed to differences in protein stability, sub-cellular distribution, and/or RNA binding and virion packaging. Here we report the first comparative biochemical studies of all the A3H variants using highly purified proteins. We show that all haplotypes were stably expressed and could be purified to homogeneity by E...
August 14, 2016: Journal of Molecular Biology
Helena Crespo, Luigi Bertolotti, Margherita Proffiti, Paolo Cascio, Fulvia Cerruti, Pier Luigi Acutis, Damián de Andrés, Ramsés Reina, Sergio Rosati
Small ruminant lentiviruses (SRLV) globally affect welfare and production of sheep and goats and are mainly controlled through elimination of infected animals, independently of the viral kinetics within the single animal. Control programs are based on highly sensitive serological tests, however the existence of low antibody responders leads to the permanent presence of seronegative infected animals in the flock, thus perpetuating the infection. On the other hand, long-term non-progressors show a detectable antibody response not indicative of a shedding animal, suggesting immune contention of infection...
August 30, 2016: Veterinary Microbiology
Xiao-Liang Zhang, Jia-Hao Song, Wei Pang, Yong-Tang Zheng
Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques...
July 18, 2016: Dong Wu Xue Yan Jiu, Zoological Research
Tegwinde Rebeca Compaore, Birama Diarra, Maleki Assih, Dorcas Obiri-Yeboah, Serge Theophile Soubeiga, Abdoul Karim Ouattara, Damehan Tchelougou, Cyrille Bisseye, Didier Romuald Bakouan, Issaka Pierre Compaore, Augustine Dembele, Wendkuuni Florencia Djigma, Jacques Simpore
BACKGROUND: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G) is a potent host defense factor, which interferes with HIV-1 and HBV. Our study had three objectives, to screen a population of HIV-1 infected and uninfected patients in Burkina Faso for HBV, to screen the population for APOBEC3G variants rs6001417, rs8177832, and rs35228531 previously described, and to analyze the effect of these three variants and their haplotypes on HIV-1/HBV co-infection in Burkina Faso...
2016: BMC Infectious Diseases
Yasuo Ariumi
Long interspersed element type 1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome, encoding a newly identified ORF0 with unknown function, ORF1p with RNA-binding activity and ORF2p with endonuclease and reverse transcriptase activities required for L1 retrotransposition. L1 utilizes an endonuclease (EN) to insert L1 cDNA into target DNA, which induces DNA double-strand breaks (DSBs). The ataxia-telangiectasia mutated (ATM) is activated by DSBs and subsequently the ATM-signaling pathway plays a role in regulating L1 retrotransposition...
2016: Frontiers in Chemistry
Belete A Desimmie, Ryan C Burdick, Taisuke Izumi, Hibiki Doi, Wei Shao, W Gregory Alvord, Kei Sato, Yoshio Koyanagi, Sara Jones, Eleanor Wilson, Shawn Hill, Frank Maldarelli, Wei-Shau Hu, Vinay K Pathak
Although APOBEC3 cytidine deaminases A3G, A3F, A3D and A3H are packaged into virions and inhibit viral replication by inducing G-to-A hypermutation, it is not known whether they are copackaged and whether they can act additively or synergistically to inhibit HIV-1 replication. Here, we showed that APOBEC3 proteins can be copackaged by visualization of fluorescently-tagged APOBEC3 proteins using single-virion fluorescence microscopy. We further determined that viruses produced in the presence of A3G + A3F and A3G + A3H, exhibited extensive comutation of viral cDNA, as determined by the frequency of G-to-A mutations in the proviral genomes in the contexts of A3G (GG-to-AG) and A3D, A3F or A3H (GA-to-AA) edited sites...
September 19, 2016: Nucleic Acids Research
Weizi Liang, Jiwei Xu, Wensu Yuan, Xuan Song, Jianyong Zhang, Wei Wei, Xiao-Fang Yu, Ying Yang
Human long interspersed elements 1 (LINE-1 or L1) is the only autonomous non-LTR retroelement in humans and has been associated with genome instability, inherited genetic diseases, and the development of cancer. Certain human APOBEC3 family proteins are known to have LINE-1 restriction activity. The mechanisms by which APOBEC3 affects LINE-1 retrotransposition are not all well characterized; here, we confirm that both A3B and A3DE have a strong ability to inhibit LINE-1 retrotransposition. A3DE interacts with LINE-1 ORF1p to target LINE-1 ribonucleoprotein particles in an RNA-dependent manner...
2016: PloS One
Zeli Zhang, Qinyong Gu, Ananda Ayyappan Jaguva Vasudevan, Anika Hain, Björn-Philipp Kloke, Sascha Hasheminasab, Daniel Mulnaes, Kei Sato, Klaus Cichutek, Dieter Häussinger, Ignacio G Bravo, Sander H J Smits, Holger Gohlke, Carsten Münk
BACKGROUND: Feline immunodeficiency virus (FIV) is a global pathogen of Felidae species and a model system for Human immunodeficiency virus (HIV)-induced AIDS. In felids such as the domestic cat (Felis catus), APOBEC3 (A3) genes encode for single-domain A3Z2s, A3Z3 and double-domain A3Z2Z3 anti-viral cytidine deaminases. The feline A3Z2Z3 is expressed following read-through transcription and alternative splicing, introducing a previously untranslated exon in frame, encoding a domain insertion called linker...
2016: Retrovirology
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