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dna damage and virus

Stephanie Trend, Barbara J Chang, Mark O'Dea, Stephen M Stick, Anthony Kicic
Antimicrobial-resistant microbes are an increasing threat to human health. In cystic fibrosis (CF), airway infections with Pseudomonas aeruginosa remain a key driver of lung damage. With few new antibiotics on the development horizon, alternative therapeutic approaches are needed against antimicrobial-resistant pathogens. Phage therapy, or the use of viruses that infect bacteria, is one proposed novel therapy to treat bacterial infections. However, the airways are complex microenvironments with unique characteristics that may affect the success of novel therapies...
2018: Frontiers in Pharmacology
Zi-Shu Chen, Xiao-Wen Cheng, Xing Wang, Dian-Hai Hou, Guo-Hua Huang
Ascoviruses are enveloped, circular, double-stranded DNA viruses that can effectively control the appetite of lepidopteran larvae, thereby reducing the consequent damage and economic losses to crops. In this study, the virion of a sequenced Heliothis virescens ascovirus 3i (HvAV-3i) strain was used to perform proteomic analysis using both in-gel and in-solution digestion. A total of 81 viral proteins, of which 67 were associated with the virions, were identified in the proteome of HvAV-3i virions. Among these proteins, 23 with annotated functions were associated with DNA/RNA metabolism/transcription, virion assembly, sugar and lipid metabolism, signalling, cellular homoeostasis and cell lysis...
December 12, 2018: Journal of General Virology
James Ahodantin, Myriam Bou-Nader, Corinne Cordier, Jérôme Mégret, Patrick Soussan, Chantal Desdouets, Dina Kremsdorf
Hepatitis B virus X protein (HBx) contributes to Hepatitis B virus (HBV)-related liver cancer. However, its impact on hepatocyte proliferation and genomic stability remains elusive. We studied the role of HBx expression on the progression of cell cycle and liver polyploidization during proliferation and liver carcinogenesis. Full-length HBx transgenic mice (FL-HBx) were developed to investigate liver ploidy as well as hepatocyte proliferation, along normal liver maturation and during cancer initiation (chemical carcinogen treatment)...
December 11, 2018: Oncogene
Marijn Knip, Manon Ms Richard, Lisa Oskam, Hylco T D van Engelen, Thomas Aalders, Frank L W Takken
Intracellular NLR (nucleotide-binding leucine-rich repeat)-type immune receptors are a fundamental aspect of plant immune systems. As infection occurs at foci, activation of immune responses is typically non-uniform and non-synchronized, hampering the systematic dissection of their cellular effects and determining their phasing. We investigated the Potato NLR Rx1 using the CESSNA (Controlled Expression of effectors for Synchronized and Systemic NLR Activation) platform. CESSNA mediated Potato Virus X coat protein (CP) expression allowed monitoring of Rx1-mediated immune responses in a quantitative, and reproducible manner...
December 8, 2018: Molecular Plant Pathology
Wenyi Gu, Surong Sun, Andrew Kahn, Dalton Dacus, Sebastian O Wendel, Nigel McMillan, Nicholas A Wallace
High risk human papillomavirus (HPV) infections are the causative agent in virtually every cervical cancer as well as a host of other anogenital and oropharyngeal malignancies. These viruses must activate DNA repair pathways to facilitate their replication, while avoiding the cell cycle arrest and apoptosis that can accompany DNA damage. HPV oncoproteins facilitate each of these goals, but also reduce genome stability. Our data dissect the cytotoxic and cytoprotective characteristics of HPV oncogenes in cervical cancer cells...
December 2, 2018: Gene
Abdul Malik, Deepak Kumar, Abdul Arif Khan, Azmat Ali Khan, Anis Ahmad Chaudhary, Syed Akhtar Husain, P Kar
Hepatitis B with precore stop codon mutation is related with severe liver damage in HBeAg negative patients. It is of utmost importance to screen the G1896A precore mutation. The study was designed to assess the impact of G1986A mutations in patients with different clinical spectra of the liver disease by PCR-LCR. 210 HBV positive patients with HBeAg negative serology of different kind of liver diseases (AVH = 72, FH = 21, CH = 79, Cirrhosis = 20 and HCC = 18) were screened. Patients were screened for the presence or absence of precore G1896A mutation by PCR-LCR...
November 2018: Saudi Journal of Biological Sciences
Lu Yang, Ming Xu, Chuan-Bao Cui, Peng-Hai Wei, Shu-Zhi Wu, Zuo-Jie Cen, Xing-Xing Meng, Qiong-Guang Huang, Zhi-Chun Xie
Background: The current study aims at using the whole genome expression profile chips for systematically investigating the diagnostic and prognostic values of excision repair cross-complementation (ERCC) genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Materials and methods: Whole genome expression profile chips were obtained from the GSE14520. The receiver-operating characteristic (ROC) curve, survival analysis, and nomogram were used to investigate the diagnostic and prognostic values of ERCC genes...
2018: Cancer Management and Research
Merle Höpken, Isabel Förster, Steffen Maune, Michael Brockmann, Oliver Schildgen, Verena Schildgen
Background: The human bocavirus (HBoV) is known to persist latently in the infected host cells and seems to replicate its DNA via the DNA damage response system, which is frequently defect in tumors and correlates with microsatellite instability (MSI). Because HBoV is able to persist in the infected tissues, induces pro-fibrotic and pro- cancerogenic cytokines in vivo and in vitro , and is detected in colorectal and lung tumors, the virus may be involved in cancerogenesis at least as a cofactor. Recently it was shown that the adenotonsillar tissue is an important site of HBoV1 persistence and replication...
2018: Frontiers in Microbiology
Hui Liu, Ke Qiu, Qiang He, Qiang Lei, Wei Lu
Herpes simplex encephalitis (HSE) is often caused by infection with herpes simplex virus 1 (HSV-1), a neurotropic double-stranded DNA virus. HSE infection always impacts the temporal and frontal lobes or limbic system, leading to edema, hemorrhage, and necrotic changes in the brain parenchyma. Additionally, patients often exhibit severe complications following antiviral treatment, including dementia and epilepsy. HSE is further associated with disruptions to the blood-brain barrier (BBB), which consists of microvascular endothelial cells, tight junctions, astrocytes, pericytes, and basement membranes...
November 19, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Yan-Ting Lin, Wei Liu, Yun He, Yun-Li Wu, Wan-Nan Chen, Xin-Jian Lin, Xu Lin
BACKGROUND/AIMS: Chronic hepatitis B virus (HBV) infection markedly increases the risk of development of hepatocellular carcinoma (HCC). Among the seven viral proteins that HBV encodes, HBV X protein (HBx) appears to have the most oncogenic potential. The mitochondria-associated HBx can induce oxidative stress in hepatocytes, leading to the production of abundant reactive oxygen species (ROS). High levels of ROS usually induce oxidative DNA damage and 8-hydroxy-2-deoxyguanosine (8-OHdG), also known as 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), which is one of the major products of DNA oxidation and an important biomarker for oxidative stress and carcinogenesis...
2018: Cellular Physiology and Biochemistry
Diletta Francesca Squarzanti, Rita Sorrentino, Manuela Miriam Landini, Andrea Chiesa, Sabrina Pinato, Francesca Rocchio, Martina Mattii, Lorenza Penengo, Barbara Azzimonti
BACKGROUND: Despite vaccination and screening measures, anogenital cancer, mainly promoted by HPV16 oncoproteins, still represents the fourth tumor and the second cause of death among women. Cell replication fidelity is the result of the host DNA damage response (DDR). Unlike many DNA viruses that promote their life cycle through the DDR inactivation, HR-HPVs encourage cells proliferation despite the DDR turned on. Why and how it occurs has been only partially elucidated. During HPV16 infection, E6 links and degrades p53 via the binding to the E6AP LXXLL sequence; unfortunately, E6 direct role in the DDR response has not clearly identified yet...
November 16, 2018: Virology Journal
Ilja Demuth, Simon K Krebs, Véronique Dutrannoy, Christian Linke, Sylvia Krobitsch, Raymonda Varon, Christine Lang, Andreas Raab, Karl Sperling, Martin Digweed
The genes, XRS2 in Saccharomyces cerevisiae and NBN in mammals, have little sequence identity at the amino acid level. Nevertheless, they are both found together with MRE11 and RAD50 in a highly conserved protein complex which functions in the repair of DNA double-strand breaks. Here, we have examined the evolutionary and functional relationship of these two genes by cross-complementation experiments. These experiments necessitated sequence correction for specific codon usage before they could be successfully conducted...
2018: PloS One
Corinne P Oechslin, Nicole Lenz, Nicole Liechti, Sarah Ryter, Philipp Agyeman, Rémy Bruggmann, Stephen L Leib, Christian M Beuret
The etiologic cause of encephalitis, meningitis or meningo-encephalitis is unknown in up to 70% of cases. Clinical shotgun metagenomics combined with host depletion is a promising technique to identify infectious etiologies of central nervous system (CNS) infections. We developed a straightforward eukaryotic host nucleic acid depletion method that preserves intact viruses and bacteria for subsequent shotgun metagenomics screening of clinical samples, focusing on cerebrospinal fluid (CSF). A surrogate CSF sample for a CNS infection paradigm was used to evaluate the proposed depletion method consisting of selective host cell lysis, followed by enzymatic degradation of the liberated genomic DNA for final depletion with paramagnetic beads...
2018: Frontiers in Cellular and Infection Microbiology
Dorota Piekna-Przybylska, Kavyasri Nagumotu, Danielle M Reid, Sanjay B Maggirwar
Reduced pericytes' coverage of endothelium in the brain is one of the structural changes leading to breach of the blood-brain barrier during HIV infection. We previously showed in central memory T (TCM ) cells that HIV latency increases cellular susceptibility to DNA damage. In this study, we investigated susceptibility of primary brain pericytes infected with HIV-1 to DNA damage in response to glutamate and TNF-α, both known to induce neuronal death during chronic inflammatory conditions. To infect pericytes, we used a single-cycle HIV-1 pseudotyped with VSV-G envelope glycoprotein and maintained the cultures until latency was established...
November 6, 2018: Journal of Neurovirology
N Sanjib Banerjee, Dianne W Moore, Thomas R Broker, Louise T Chow
Human papillomaviruses (HPVs) cause epithelial proliferative diseases. Persistent infection of the mucosal epithelia by the high-risk genotypes can progress to high-grade dysplasia and cancers. Viral transcription and protein activities are intimately linked to regulation by histone acetyltransferases and histone deacetylases (HDACs) that remodel chromatin and regulate gene expression. HDACs are also essential to remodel and repair replicating chromatin to enable the progression of replication forks. As such, Vorinostat (suberoylanilide hydroximic acid), and other pan-HDAC inhibitors, are used to treat lymphomas...
November 1, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hang T Pham, Tram T T Nguyen, Lap P Nguyen, Sang-Seop Han, Yun-Sook Lim, Soon B Hwang
Hepatitis C virus (HCV) infection may cause chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV exploits cellular machineries to establish persistent infection. Herein we demonstrated that ubiquitin conjugating enzyme E2S (UBE2S), a member of ubiquitin conjugating enzyme family (E2s), was downregulated by ER stress caused by HCV in Huh7 cells. UBE2S interacted with domain I of HCV NS5A and degraded NS5A protein through Lys11-linked proteasome-dependent pathway. Overexpression of UBE2S suppressed viral propagation, while depletion of UBE2S expression increased viral infectivity...
October 31, 2018: Journal of Virology
Arturo Ciccullo, F R Ponziani, E Maiolo, F Pallavicini, M Pompili
BACKGROUND: Hepatitis B virus (HBV) reactivation is commonly observed in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Recent guidelines recommend antiviral prophylaxis to be continued for up to 12 months after the discontinuation of the anticancer regimen. CASE PRESENTATION: We report a case of a patient who underwent antiviral prophylaxis for 26 months after the discontinuation of a rituximab-containing chemotherapy regimen for a lymphoma and was admitted in the infectious diseases department with a 3-day history of jaundice, itching, and dark urine...
October 27, 2018: Infection
Jasmine V E Chan-Hyams, Janine N Copp, Jeff B Smaill, Adam V Patterson, David F Ackerley
Gene-directed enzyme-prodrug therapy (GDEPT) employs tumour-tropic vectors including viruses and bacteria to deliver a genetically-encoded prodrug-converting enzyme to the tumour environment, thereby sensitising the tumour to the prodrug. Nitroreductases, able to activate a range of promising nitroaromatic prodrugs to genotoxic metabolites, are of great interest for GDEPT. The bystander effect (cell-to-cell transfer of activated prodrug metabolites) has been quantified for some nitroaromatic prodrugs in mixed multilayer human cell cultures, however while these provide a good model for viral DEPT (VDEPT) they do not inform on the ability of these prodrug metabolites to exit bacterial vectors (relevant to bacterial-DEPT (BDEPT))...
December 2018: Biochemical Pharmacology
Daphne van Elsland, Jacques Neefjes
Infections are estimated to contribute to 20% of all human tumours. These are mainly caused by viruses, which explains why a direct bacterial contribution to cancer formation has been largely ignored. While epidemiological data link bacterial infections to particular cancers, tumour formation is generally assumed to be solely caused by the ensuing inflammation responses. Yet, many bacteria directly manipulate their host cell in various phases of their infection cycle. Such manipulations can affect host cell integrity and can contribute to cancer formation...
November 2018: EMBO Reports
Mariko Murata
Infection and inflammation account for approximately 25% of cancer-causing factors. Inflammation-related cancers are characterized by mutagenic DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. Our previous studies demonstrated the formation of 8-oxodG and 8-nitroguanine in the tissues of cancer and precancerous lesions due to infection (e.g., Opisthorchis viverrini-related cholangiocarcinoma, Schistosoma haematobium-associated bladder cancer, Helicobacter pylori-infected gastric cancer, human papillomavirus-related cervical cancer, Epstein-Barr virus-infected nasopharyngeal carcinoma) and pro-inflammatory factors (e...
October 20, 2018: Environmental Health and Preventive Medicine
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