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dna damage and virus

Qi Liu, Lin Ma, Trevor Jones, Luis Palomero, Miguel Angel Pujana, Haydeliz Martinez-Ruiz, Patrick K Ha, John Murnane, Isabel Cuartas, Joan Seoane, Michael Baumann, Annett Linge, Mary Helen Barcellos-Hoff
PURPOSE: Following cytotoxic therapy, 70% of patients with human papillomavirus (HPV) positive oropharyngeal head and neck squamous cell carcinoma (HNSCC) are alive at 5 years compared to 30% of those with similar HPV-negative cancer, which is thought to be due to dysregulation of DNA repair. Loss of transforming growth factor β (TGFβ) signaling is a poorly studied consequence of HPV that could contribute to this phenotype. EXPERIMENTAL DESIGN: Human HNSCC cell lines (n=9), patient-derived xenografts (n=9), tissue microarray (n=194), TCGA expression data and primary tumor specimens (n=10) were used to define the relationship between TGFβ competency, response to DNA damage, and type of DNA repair...
August 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Stephen M Rawlinson, Tianyue Zhao, Ashley M Rozario, Christina L Rootes, Paul J McMillan, Anthony W Purcell, Amanda Woon, Glenn A Marsh, Kim G Lieu, Lin-Fa Wang, Hans J Netter, Toby D M Bell, Cameron R Stewart, Gregory W Moseley
Recent studies indicate that nucleoli play critical roles in the DNA-damage response (DDR) via interaction of DDR machinery including NBS1 with nucleolar Treacle protein, a key mediator of ribosomal RNA (rRNA) transcription and processing. Here, using proteomics, confocal and single molecule super-resolution imaging, and infection under biosafety level-4 containment, we show that this nucleolar DDR pathway is targeted by infectious pathogens. We find that the matrix proteins of Hendra virus and Nipah virus, highly pathogenic viruses of the Henipavirus genus in the order Mononegavirales, interact with Treacle and inhibit its function, thereby silencing rRNA biogenesis, consistent with mimicking NBS1-Treacle interaction during a DDR...
August 3, 2018: Nature Communications
Mario Hupfeld, Despoina Trasanidou, Livia Ramazzini, Jochen Klumpp, Martin J Loessner, Samuel Kilcher
CRISPR-Cas systems provide bacteria with adaptive immunity against invading DNA elements including bacteriophages and plasmids. While CRISPR technology has revolutionized eukaryotic genome engineering, its application to prokaryotes and their viruses remains less well established. Here we report the first functional CRISPR-Cas system from the genus Listeria and demonstrate its native role in phage defense. LivCRISPR-1 is a type II-A system from the genome of L. ivanovii subspecies londoniensis that uses a small, 1078 amino acid Cas9 variant and a unique NNACAC protospacer adjacent motif...
July 27, 2018: Nucleic Acids Research
Liqian Zhu, Xiaotian Fu, Chen Yuan, Xinyi Jiang, Gaiping Zhang
Bovine herpesvirus 1 (BoHV-1) is an important pathogen of cattle that causes lesions in mucosal surfaces, genital tracts and nervous systems. As a novel oncolytic virus, BoHV-1 infects and kills numerous human tumor cells. However, the mechanisms underlying the virus-induced cell damages are not fully understood. In this study, we demonstrated that virus infection of MDBK cells induced high levels of DNA damage, because the percentage of comet tail DNA (tailDNA%) determined by comet assay, a direct indicator of DNA damage, and the levels of 8-hydroxyguanine (8-oxoG) production, an oxidative DNA damage marker, consistently increased following the virus infection...
July 26, 2018: Viruses
Takashi Ohama
This review presents the accumulating evidence for the roles of protein phosphatase 6 (PP6) in cell cycle, DNA damage repair, inflammatory signaling, lymphocyte development, virus infection, tumor formation/progression, cell/tissue size, and non-coding RNA-mediated regulation. PP6 is an evolutionarily conserved and ubiquitously expressed Ser/Thr protein phosphatase most closely related to protein phosphatase 2A (PP2A) and protein phosphatase 4 (PP4). Although abundantly expressed in cells with multiple roles in cellular signaling, PP6 has received less attention than its close relative PP2A...
July 21, 2018: Biochimica et Biophysica Acta
Mohamed Mlih, Mobina Khericha, Christine Birdwell, A Phillip West, Jason Karpac
Aging is characterized by degeneration of unique tissues. However, dissecting the interconnectedness of tissue aging remains a challenge. Here, we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues. Utilizing this model, we uncovered a cytokine-Diedel-that, when secreted from muscle or adipose, can attenuate age-related intestinal tissue degeneration by promoting proliferative homeostasis of stem cells. Diedel is both necessary and sufficient to limit tissue degeneration and regulate lifespan...
July 2018: PLoS Biology
Kinjal Majumder, Juexin Wang, Maria Boftsi, Matthew S Fuller, Jordan E Rede, Trupti Joshi, David J Pintel
We have developed a generally adaptable, novel high-throughput Viral Chromosome Conformation Capture assay (V3C-seq) for use in trans that allows genome-wide identification of the direct interactions of a lytic virus genome with distinct regions of the cellular chromosome. Upon infection, we found that the parvovirus Minute Virus of Mice (MVM) genome initially associated with sites of cellular DNA damage that in mock-infected cells also exhibited DNA damage as cells progressed through S-phase. As infection proceeded, new DNA damage sites were induced, and virus subsequently also associated with these...
July 20, 2018: ELife
Soňa Vyskočilová, Wee Tek Tay, Sharon van Brunschot, Susan Seal, John Colvin
Bemisia tabaci is a cryptic whitefly-species complex that includes some of the most damaging pests and plant-virus vectors of a diverse range of food and fibre crops worldwide. We combine experimental evidence of: (i) differences in reproductive compatibility, (ii) hybrid verification using a specific nuclear DNA marker and hybrid fertility confirmation and (iii) high-throughput sequencing-derived mitogenomes, to show that the "Mediterranean" (MED) B. tabaci comprises at least two distinct biological species; the globally invasive MED from the Mediterranean Basin and the "African silver-leafing" (ASL) from sub-Saharan Africa, which has no associated invasion records...
July 18, 2018: Scientific Reports
Vanessa Kaplum, Anelise C Ramos, Marcia E L Consolaro, Maria A Fernandez, Tânia Ueda-Nakamura, Benedito P Dias-Filho, Sueli de Oliveira Silva, João C P de Mello, Celso V Nakamura
Cervical cancer is the fourth most common cancer that affects women, mainly through human papilloma virus (HPV) infection with high-risk HPV16 and HPV18. The present study investigated the in vitro anticancer activity and mechanism of action of a proanthocyanidin polymer-rich fraction of Stryphnodendron adstringens (F2) in cervical cancer cell lines, including HeLa (HPV18-positive), SiHa (HPV16-positive), and C33A (HPV-negative) cells, and also evaluated in vivo anticancer activity. In vitro , cell viability was determined by the MTT assay...
2018: Frontiers in Pharmacology
Jill A Dembowski, Neal A DeLuca
Herpesviruses utilize multiple mechanisms to redirect host proteins for use in viral processes and to avoid recognition and repression by the host. To investigate dynamic interactions between herpes simplex virus type 1 (HSV-1) DNA and viral and host proteins throughout infection, we developed an approach to identify proteins that associate with the infecting viral genome from nuclear entry through packaging. To accomplish this, virus stocks were prepared in the presence of ethynyl-modified nucleotides to enable covalent tagging of viral genomes after infection for analysis of viral genome-protein interactions by imaging or affinity purification...
July 17, 2018: MBio
D P Devanand
PURPOSE OF REVIEW: Viruses, particularly herpes simplex virus (HSV), may be a cause of Alzheimer's disease (AD). The evidence supporting the viral hypothesis suggests that antiviral treatment trials, which have not been conducted, are warranted. RECENT FINDINGS: HSV1 (oral herpes) and HSV2 (genital herpes) can trigger amyloid aggregation, and their DNA is common in amyloid plaques. HSV1 reactivation is associated with tau hyperphosphorylation and possibly tau propagation...
July 14, 2018: Current Neurology and Neuroscience Reports
Matthew D Weitzman, Amélie Fradet-Turcotte
Viral DNA genomes have limited coding capacity and therefore harness cellular factors to facilitate replication of their genomes and generate progeny virions. Studies of viruses and how they interact with cellular processes have historically provided seminal insights into basic biology and disease mechanisms. The replicative life cycles of many DNA viruses have been shown to engage components of the host DNA damage and repair machinery. Viruses have evolved numerous strategies to navigate the cellular DNA damage response...
July 11, 2018: Annual Review of Virology
Chelsey C Spriggs, Luis Z Blanco, Kruti P Maniar, Laimonis A Laimins
Human papillomaviruses (HPVs) are DNA viruses with epithelial tropism. High-risk types of HPV are the causative agents of the majority of cervical cancers and are responsible for a number of other anogenital as well as oropharyngeal cancers. The life cycle of HPV is closely linked to the differentiation state of its host cell and is dependent on the activation of specific pathways of the DNA damage response. Several proteins from the ataxia telangiectasia mutated and the ataxia telangiectasia mutated and Rad3-related DNA repair pathways, which are essential for maintaining genomic stability in cells, are upregulated in HPV-positive cells and are required for viral replication...
July 10, 2018: International Journal of Gynecological Pathology
Zhibin Sun, Jiadong Fan, Haoyuan Li, Huajie Liu, Daewoong Nam, Chan Kim, Yoonhee Kim, Yubo Han, Jianhua Zhang, Shengkun Yao, Jaehyun Park, Sunam Kim, Kensuke Tono, Makina Yabashi, Tetsuya Ishikawa, Changyong Song, Chunhai Fan, Huaidong Jiang
It has been proposed that the radiation damage to biological particles and soft condensed matter can be overcome by ultrafast and ultraintense X-ray free-electron lasers (FELs) with short pulse durations. The successful demonstration of the "diffraction-before-destruction" concept has made single-shot diffraction imaging a promising tool to achieve high resolutions under the native states of samples. However, the resolution is still limited because of the low signal-to-noise ratio, especially for biological specimens such as cells, viruses, and macromolecular particles...
July 20, 2018: ACS Nano
San Juan López Cristina, Casado Martín Marta, González Sánchez Mercedes, Porcel Martín Almudena, Hernández Martínez Álvaro, Vega Sáenz Jose Luis, Parrón Carreño Tesifón
Backgrounds/Aims: The objective of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis. Methods: A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant...
July 4, 2018: Clinical and Molecular Hepatology
Seemana Bhattacharya, Dipankar Chakraborty, Malini Basu, Mrinal K Ghosh
Herpesvirus-associated ubiquitin-specific protease (HAUSP) is a USP family deubiquitinase. HAUSP is a protein of immense biological importance as it is involved in several cellular processes, including host-virus interactions, oncogenesis and tumor suppression, DNA damage and repair processes, DNA dynamics and epigenetic modulations, regulation of gene expression and protein function, spatio-temporal distribution, and immune functions. Since its discovery in the late 1990s as a protein interacting with a herpes virus regulatory protein, extensive studies have assessed its complex roles in p53-MDM2-related networks, identified numerous additional interacting partners, and elucidated the different roles of HAUSP in the context of cancer, development, and metabolic and neurological pathologies...
2018: Signal Transduction and Targeted Therapy
Gulinisha Aihemaiti, Morito Kurata, Daichi Nogawa, Akiko Yamamoto, Tatsunori Mineo, Iichiroh Onishi, Yuko Kinowaki, Xiao-Hai Jin, Anna Tatsuzawa, Naoyuki Miyasaka, Masanobu Kitagawa, Kouhei Yamamoto
Highly malignant tumors overexpress the minichromosome maintenance 2 (MCM2) protein in the nucleus, which is associated with advanced tumor grade, advanced stage, and poor prognosis. In this study, we showed that MCM2 is highly expressed in clinical samples of ovarian clear cell carcinoma. Although MCM2 expression was mainly localized to the nuclei as in other cancers, a few cases exhibited cytoplasmic localization of MCM2. Surprisingly, tumor samples with cytoplasmic MCM2 demonstrated excellent prognosis, showing 100% survival during the observation period of more than 200 months...
June 15, 2018: Oncotarget
Vishakha Tiwarekar, Julia Wohlfahrt, Markus Fehrholz, Claus-Jürgen Scholz, Susanne Kneitz, Jürgen Schneider-Schaulies
We found earlier that ectopic expression of the cytidine deaminase APOBEC3G (A3G) in Vero cells inhibits measles (MV), respiratory syncytial and mumps virus, while the mechanism of inhibition remained unclear. A microarray analysis revealed that in A3G transduced Vero cells several cellular transcripts were differentially expressed suggesting that A3G regulates the expression of host factors. One of the best up-regulated host cell factors, REDD1 (regulated in development and DNA damage response-1, also called DDIT4), reduced MV replication ∼10 fold upon over-expression in Vero cells...
June 20, 2018: Journal of Virology
Safder S Ganaie, Jianming Qiu
Parvovirus B19 (B19V) is pathogenic to humans and causes bone marrow failure diseases and various other inflammatory disorders. B19V infection exhibits high tropism for human erythroid progenitor cells (EPCs) in the bone marrow and fetal liver. The exclusive restriction of B19V replication to erythroid lineage cells is partly due to the expression of receptor and co-receptor(s) on the cell surface of human EPCs and partly depends on the intracellular factors essential for virus replication. We first summarize the latest developments in the viral entry process and the host cellular factors or pathways critical for B19V replication...
2018: Frontiers in Cellular and Infection Microbiology
Xianglong Yu, Zhenzhong Wang, Hao Chen, Xiaoyu Niu, Yanguo Dou, Jing Yang, Yi Tang, Youxiang Diao
Hydropericardium hepatitis syndrome (HHS) is a lethal disease caused by Fowl adenovirus serotype 4(FAdV-4) that mainly infects 3- to 6-week-old broiler chicks. In 2015, an infectious disease characterized similar symptom to HHS in broilers outbroke in commercial duck flocks in Shandong province. FAdV-4 was isolated from naturally infected ducks and determined by polymerase chain reaction (PCR) amplification and DNA sequence analysis. In order to investigate the effect of FAdV-4 infection on muscovy ducks, we determined and characterized the FAdV-4 Isolate, and assessed its pathogenicity...
2018: Frontiers in Microbiology
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