Search results for " REPLICATION"
showing 10 items of 406 documents
Widespread transcriptional gene inactivation initiated by a repair intermediate of 8-oxoguanine.
2016
DNA damage can significantly modulate expression of the affected genes either by direct structural interference with transcription components or as a collateral outcome of cellular repair attempts. Thus, DNA glycosylases of the base excision repair (BER) pathway have been implicated in negative transcriptional response to several spontaneously generated DNA base modifications, including a common oxidative DNA base modification 8-oxoguanine (8-oxoG). Here, we report that single 8-oxoG situated in the non-transcribed DNA strand of a reporter gene has a pronounced negative effect on transcription, driven by promoters of various strength and with different structural properties, including viral…
8-Oxo-7,8-dihydroguanine in DNA does not constitute a barrier to transcription, but is converted into transcription-blocking damage by OGG1.
2011
The common DNA base modification 8-oxo-7,8-dihydroguanine (8-oxo-G) affects the efficiency and fidelity of transcription. We constructed plasmid substrates carrying single 8-oxo-G residues, specifically positioned in the transcribed or the non-transcribed DNA strands, to investigate their effects on the expression of an EGFP reporter gene and to explore the role of base excision repair in the mechanism of transcription inhibition. We report that 8-oxo-G does not directly block transcription in cells, since a single 8-oxo-G in the transcribed DNA strand did not reduce the EGFP expression levels in repair-deficient (OGG1-null) mouse embryonic fibroblast cell lines. Rather, inhibition of trans…
Regression of advanced rat and human gliomas by local or systemic treatment with oncolytic parvovirus H-1 in rat models
2010
Oncolytic virotherapy is a potential treatment modality under investigation for various malignancies including malignant brain tumors. Unlike some other natural or modified viruses that show oncolytic activity against cerebral neoplasms, the rodent parvovirus H-1 (H-1PV) is completely apathogenic in humans. H-1PV efficiently kills a number of tumor cells without harm to corresponding normal ones. In this study, the concept of H-1PV-based virotherapy of glioma was tested for rat (RG-2 cell-derived) and for human (U87 cell-derived) gliomas in immunocompetent and immunodeficient rat models, respectively. Large orthotopic rat and human glioma cell-derived tumors were treated with either single …
Klinische Bedeutung des Hepatitis-B-Virus-DNS-Nachweises im Serum von Kindern mit chronischer Hepatitis B
1992
206 sera from 172 children with chronic hepatitis B infection were tested for HBV DNA by dot blot hybridization. 111 were positive and 95 negative for HBV DNA. 103 (78.6%) of the positive patients had HBeAg and 5 (7.7%) anti-HBe. In 60 (92.3%) of the anti-HBe positive sera no HBV DNA could be detected. Children with elevated liver enzymes had HBV DNA in 80.1%, whereas in 71.6% of the chronic HBsAg carriers with normal liver enzymes no HBV DNA was found. In 87 of the 95 dot blot negative patients polymerase chain reaction was performed. 73 (83.9%) children of this group were HBV DNA positive. All HBeAg positive patients and those with elevated aminotransferases had HBV DNA in their serum. 56…
Translation of hepatitis B virus (HBV) surface proteins from the HBV pregenome and precore RNAs in Semliki Forest virus-driven expression.
2004
Hepatitis B virus (HBV) pregenome RNA (pgRNA) serves as a translation template for the HBV core (HBc) protein and viral polymerase (Pol). HBV precore RNA (pcRNA) directs the synthesis of the precore (preC) protein, a precursor of the hepatitis B e antigen (HBeAg). pgRNA and pcRNA were expressed in the Semliki Forest virus (SFV) expression system. Besides the HBc and preC proteins, there was revealed the synthesis of all three forms of HBV surface (HBs) proteins: long (LHBs), middle (MHBs) and short (SHBs), the start codons of which are located more than 1000 nt downstream of the HBc and preC start codons. Moreover, other HBV templates, such as 3′-truncated pgRNA lacking 3′ direct repeat and…
Polyalbumin receptors, hepatitis B surface antigen (HBsAg), and HBsAg/IgM complexes in HBsAg positive patients with and without delta superinfection.
1985
Receptors for polymerized human albumin are found at high litres during high-level hepatitis B virus (HBV) replication and in small amounts in chronic low-level infection. Complexes between hepatitis B surface antigen (HBsAg) and IgM without specificity for HbsAg are expressed in a pattern similar to that of receptors. Anti-albumin antibodies could be involved in their formation. Delta infection depresses the synthesis of gene products of HBV. To assess whether delta modifies the expression of receptors on HBsAg and the level of HBsAg/IgM complexes, and if anti-albumin antibodies are actually part of the complex, we tested sera from 86 subjects with acute and chronic HBV infection. Our find…
Mutations in DNA Binding and Transactivation Domains Affect the Dynamics of Parvovirus NS1 Protein
2013
ABSTRACT The multifunctional replication protein of autonomous parvoviruses, NS1, is vital for viral genome replication and for the control of viral protein production. Two DNA-interacting domains of NS1, the N-terminal and helicase domains, are necessary for these functions. In addition, the N and C termini of NS1 are required for activation of viral promoter P38. By comparison with the structural and biochemical data from other parvoviruses, we identified potential DNA-interacting amino acid residues from canine parvovirus NS1. The role of the identified amino acids in NS1 binding dynamics was studied by mutagenesis, fluorescence recovery after photobleaching, and computer simulations. Mu…
Immune activation promotes evolutionary conservation of T-cell epitopes in HIV-1.
2013
The immune system should constitute a strong selective pressure promoting viral genetic diversity and evolution. However, HIV shows lower sequence variability at T-cell epitopes than elsewhere in the genome, in contrast with other human RNA viruses. Here, we propose that epitope conservation is a consequence of the particular interactions established between HIV and the immune system. On one hand, epitope recognition triggers an anti-HIV response mediated by cytotoxic T-lymphocytes (CTLs), but on the other hand, activation of CD4(+) helper T lymphocytes (TH cells) promotes HIV replication. Mathematical modeling of these opposite selective forces revealed that selection at the intrapatient l…
Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription.
2019
Objective: The HBV HBx regulatory protein is required for transcription from the covalently closed circular DNA (cccDNA) minichromosome and affects the epigenetic control of both viral and host cellular chromatin. Design: We explored, in relevant cellular models of HBV replication, the functional consequences of HBx interaction with DLEU2, a long non-coding RNA (lncRNA) expressed in the liver and increased in human hepatocellular carcinoma (HCC), in the regulation of host target genes and the HBV cccDNA. Results: We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx…
Overexpression of STAT-1 by adenoviral gene transfer does not inhibit hepatitis B virus replication.
2006
Objectives Interferons are known to inhibit the replication of hepatitis B viruses (HBV) in several animal models in vitro and in vivo as well in humans. The STAT-1 protein plays a central role in the biological activity of both type I and type II interferons. The lack of functional STAT-1 renders cells and organisms susceptible to bacterial and viral infectious agents. We analysed whether the overexpression of STAT-1 protein enhances the biological interferon response and whether it elicits antiviral acitivity against HBV in vitro. Methods To achieve an efficient STAT-1 overexpression in primary liver cells and hepatoma cells, we generated a recombinant, replication-deficient adenovirus ex…