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Volume 1, December
 
 

Pathogens, Volume 1, Issue 1 (September 2012) – 6 articles , Pages 1-64

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Article
Arginine Methyltransferases Are Regulated by Epstein-Barr Virus in B Cells and Are Differentially Expressed in Hodgkin’s Lymphoma
by Sarah Leonard, Naheema Gordon, Nikki Smith, Martin Rowe, Paul G. Murray and Ciarán B. Woodman
Pathogens 2012, 1(1), 52-64; https://doi.org/10.3390/pathogens1010052 - 19 Sep 2012
Cited by 16 | Viewed by 7126
Abstract
Although there is increasing evidence that aberrant expression of those enzymes which control protein arginine methylation contribute to carcinogenesis, their de-regulation by oncogenic viruses in primary cells has yet to be reported. We first show that the protein arginine methyltransferases, CARM1, PRMT1 and [...] Read more.
Although there is increasing evidence that aberrant expression of those enzymes which control protein arginine methylation contribute to carcinogenesis, their de-regulation by oncogenic viruses in primary cells has yet to be reported. We first show that the protein arginine methyltransferases, CARM1, PRMT1 and PRMT5 are strongly expressed in Hodgkin Reed-Sternberg (HRS) cells, and up-regulated in Hodgkin's lymphoma (HL) cell lines. Given that Epstein-Barr virus (EBV) can be detected in approximately 50% of primary HL, we next examined how EBV infection of germinal centre (GC) B cells, the presumptive precursors of HRS cells, modulated the expression of these proteins. EBV infection of GC B cells was followed by the up-regulation of CARM1, PRMT1 and PRMT5, and by the down-regulation of the arginine deiminase, PADI4. Latent membrane protein 1 (LMP1), the major EBV transforming gene was shown to induce PRMT1 in GC B cells and in a stably transfected B cell line. The recent development of compounds which inhibit PRMT-mediated reactions provides a compelling case for continuing to dissect the contribution of virus induced changes in these proteins to lymphomagenesis. Full article
(This article belongs to the Special Issue Infection and Cancer)
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323 KiB  
Review
Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a “Bookmarking” Oncoprotein that Alters the Host Cell Epigenotype?
by Hans Helmut Niller and Janos Minarovits
Pathogens 2012, 1(1), 37-51; https://doi.org/10.3390/pathogens1010037 - 17 Sep 2012
Cited by 12 | Viewed by 6786
Abstract
EBNA1, a nuclear protein expressed in all EBV-associated neoplasms is indispensable for the maintenance of the viral episomes in latently infected cells. EBNA1 may induce genetic alterations by upregulating cellular recombinases, production of reactive oxygen species (ROS) and affecting p53 levels and function. [...] Read more.
EBNA1, a nuclear protein expressed in all EBV-associated neoplasms is indispensable for the maintenance of the viral episomes in latently infected cells. EBNA1 may induce genetic alterations by upregulating cellular recombinases, production of reactive oxygen species (ROS) and affecting p53 levels and function. All these changes may contribute to tumorigenesis. In this overview we focus, however, on the epigenetic alterations elicited by EBNA1 by drawing a parallel between EBNA1 and the FoxA family of pioneer transcription factors. Both EBNA1 and FoxA induce local DNA demethylation, nucleosome destabilization and bind to mitotic chromosomes. Local DNA demethylation and nucleosome rearrangement mark active promoters and enhancers. In addition, EBNA1 and FoxA, when associated with mitotic chromatin may “bookmark” active genes and ensure their reactivation in postmitotic cells (epigenetic memory). We speculate that DNA looping induced by EBNA1-EBNA1 interactions may reorganize the cellular genome. Such chromatin loops, sustained in mitotic chromatin similarly to the long-distance interactions mediated by the insulator protein CTCF, may also mediate the epigenetic inheritance of gene expression patterns. We suggest that EBNA1 has the potential to induce patho-epigenetic alterations contributing to tumorigenesis. Full article
(This article belongs to the Special Issue Infection and Cancer)
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Article
Evaluation of the Cobas 4800 HPV Test for Detecting High-Risk Human Papilloma-Virus in Cervical Cytology Specimens
by Isabella W. Martin, Heather B. Steinmetz, Claudine L. Lefferts, Larry J. Dumont, Laura J. Tafe and Gregory J. Tsongalis
Pathogens 2012, 1(1), 30-36; https://doi.org/10.3390/pathogens1010030 - 12 Sep 2012
Cited by 7 | Viewed by 7550
Abstract
As new platforms for high-risk strains of human papillomavirus (HR HPV) testing are introduced into the clinical laboratory, it is important to verify their performance and agreement. In this validation study, post-aliquot cervical cytopathology specimens (n = 226) were used to analyze agreement [...] Read more.
As new platforms for high-risk strains of human papillomavirus (HR HPV) testing are introduced into the clinical laboratory, it is important to verify their performance and agreement. In this validation study, post-aliquot cervical cytopathology specimens (n = 226) were used to analyze agreement between the Invader HPV ASR assay (Hologic) and the recently FDA-approved Cobas 4800 high-risk HPV assay (Roche). Residual sample from 92 Invader positive and 134 Invader negative samples were analyzed with the Cobas 4800 test. Discordant results were further analyzed by Linear Array HPV genotype testing (Roche). To assess intra- and inter-run precision, 31 Invader positive samples were run in duplicate on the Cobas 4800 by different operators over multiple days and purchased HR HPV DNA control was run in ten replicates. Cross-contamination during cytology processing was evaluated by spiking 6 Invader negative samples with different volumes of Acrometrix HPV High Risk Positive Control and analyzed on the Cobas with 4 negative samples in between. There was significant discordance between the assays (p < 0.001; exact McNemar X2 test), with overall agreement of 82%. Of the 92 Invader positive samples, 58 (63%) were positive with the Cobas assay, while 34 (37%) were negative. Of the 134 Invader negative samples, 6 (4%) were positive with the Cobas while 128 (96%) were negative. The observed discordance may be attributed to the previously described false positive rate of the Invader ASR assay. The Cobas 4800 high-risk HPV assay is a viable new tool for use in the clinical setting to identify high-risk HPV. Full article
(This article belongs to the Special Issue Infection and Cancer)
642 KiB  
Article
Roles for wbtC, wbtI, and kdtA Genes in Lipopolysaccharide Biosynthesis, Protein Glycosylation, Virulence, and Immunogenicity in Francisella tularensis Strain SCHU S4
by Susan M. Twine, Evguenii Vinogradov, Helena Lindgren, Anders Sjostedt and J. Wayne Conlan
Pathogens 2012, 1(1), 12-29; https://doi.org/10.3390/pathogens1010012 - 10 Sep 2012
Cited by 17 | Viewed by 6459
Abstract
Using a strategy of gene deletion mutagenesis, we have examined the roles of genes putatively involved in lipopolysaccharide biosynthesis in the virulent facultative intracellular bacterial pathogen, Francisella tularensis subspecies tularensis, strain SCHU S4 in LPS biosynthesis, protein glycosylation, virulence and immunogenicity. One [...] Read more.
Using a strategy of gene deletion mutagenesis, we have examined the roles of genes putatively involved in lipopolysaccharide biosynthesis in the virulent facultative intracellular bacterial pathogen, Francisella tularensis subspecies tularensis, strain SCHU S4 in LPS biosynthesis, protein glycosylation, virulence and immunogenicity. One mutant, ∆wbtI, did not elaborate a long chain O-polysaccharide (OPS), was completely avirulent for mice, and failed to induce a protective immune response against challenge with wild type bacteria. Another mutant, ∆wbtC, produced a long chain OPS with altered chemical and electrophoretic characteristics. This mutant showed markedly reduced glycosylation of several known glycoproteins. Additionally this mutant was highly attenuated, and elicited a protective immune response against systemic, but not respiratory challenge with wild type SCHU S4. A third mutant, ∆kdtA, produced an unconjugated long chain OPS, lacking a detectable core structure, and which was not obviously expressed at the surface. It was avirulent and elicited partial protection against systemic challenge only. Full article
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Article
Interaction of Phenol-Soluble Modulins with Phosphatidylcholine Vesicles
by Anthony C. Duong, Gordon Y. C. Cheung and Michael Otto
Pathogens 2012, 1(1), 3-11; https://doi.org/10.3390/pathogens1010003 - 20 Jul 2012
Cited by 15 | Viewed by 7351
Abstract
Several members of the staphylococcal phenol-soluble modulin (PSM) peptide family exhibit pronounced capacities to lyse eukaryotic cells, such as neutrophils, monocytes, and erythrocytes. This is commonly assumed to be due to the amphipathic, α-helical structure of PSMs, giving PSMs detergent-like characteristics and allowing [...] Read more.
Several members of the staphylococcal phenol-soluble modulin (PSM) peptide family exhibit pronounced capacities to lyse eukaryotic cells, such as neutrophils, monocytes, and erythrocytes. This is commonly assumed to be due to the amphipathic, α-helical structure of PSMs, giving PSMs detergent-like characteristics and allowing for a relatively non-specific destruction of biological membranes. However, the capacities of PSMs to lyse synthetic phospholipid vesicles have not been investigated. Here, we analyzed lysis of synthetic phosphatidylcholine (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC) vesicles by all Staphylococcus aureus and S. epidermidis PSMs. In addition, we investigated the lytic capacities of culture filtrates obtained from different S. aureus PSM deletion mutants toward POPC vesicles. Our results show that all staphylococcal PSMs have phospholipid vesicle-lysing activity and the capacity of S. aureus culture filtrate to lyse POPC vesicles is exclusively dependent on PSMs. Notably, we observed largely differing capacities among PSM peptides to lyse POPC vesicles. Interestingly, POPC vesicle-lytic capacities did not correlate with those previously seen for the lysis of eukaryotic cells. For example, the β-type PSMs were strongly lytic for POPC vesicles, but are known to exhibit only very low lytic capacities toward neutrophils and erythrocytes. Thus our results also suggest that the interaction between PSMs and eukaryotic membranes is more specific than previously assumed, potentially depending on additional structural features of those membranes, such as phospholipid composition or yet unidentified docking molecules. Full article
(This article belongs to the Special Issue Feature Papers)
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114 KiB  
Editorial
Pathogens: A New Open Access Journal Serving All Those Interested in Infectious Disease
by Lawrence S. Young
Pathogens 2012, 1(1), 1-2; https://doi.org/10.3390/pathogens1010001 - 29 Sep 2011
Viewed by 4994
Abstract
Infection ranks alongside cardiovascular disease as the major cause of human death across the world. Word Health Organization data for 2002 shows that 26% of all deaths, almost 15 million in number, were due to infectious disease with HIV/AIDS, TB and malaria being [...] Read more.
Infection ranks alongside cardiovascular disease as the major cause of human death across the world. Word Health Organization data for 2002 shows that 26% of all deaths, almost 15 million in number, were due to infectious disease with HIV/AIDS, TB and malaria being the top three responsible infections. A significant proportion of these deaths were due to lower respiratory infections and diarrheal diseases in children. The worldwide morbidity associated with infectious disease is incalculable. When considered along with the consequences of infection in animals, it is hard to imagine any other disease that has such a significant impact on our lives―on health systems, on agriculture and on world economics. Our understanding of the agents responsible for infections―bacteria, fungi, parasites, prions and viruses―has an interesting history that heralds the great developments in modern biology and demonstrates how an understanding of disease pathogenesis can lead to successful prophylactic and therapeutic interventions. Van Leeuwenhoek’s first observation of bacteria under the light microscope, John Snow’s investigations tracing the source of a cholera epidemic in Victorian London’s Soho and Pasteur’s vaccines for rabies and anthrax contributed to an acceptance of the germ theory of disease and to the rational, scientific application of this knowledge to develop innovative disease control measures ranging from hygienic practices to antibiotics. [...] Full article
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