Open AccessArticle
Genome Characterization of a Pathogenic Porcine Rotavirus B Strain Identified in Buryat Republic, Russia in 2015
Pathogens 2018, 7(2), 46; doi:10.3390/pathogens7020046 (registering DOI) -
Abstract
An outbreak of enteric disease of unknown etiology with 60% morbidity and 8% mortality in weaning piglets occurred in November 2015 on a farm in Buryat Republic, Russia. Metagenomic sequencing revealed the presence of rotavirus B in feces from diseased piglets while no
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An outbreak of enteric disease of unknown etiology with 60% morbidity and 8% mortality in weaning piglets occurred in November 2015 on a farm in Buryat Republic, Russia. Metagenomic sequencing revealed the presence of rotavirus B in feces from diseased piglets while no other pathogens were identified. Clinical disease was reproduced in experimentally infected piglets, yielding the 11 RVB gene segments for strain Buryat15, with an RVB genotype constellation of G12-P[4]-I13-R4-C4-M4-A8-N10-T4-E4-H7. This genotype constellation has also been identified in the United States. While the Buryat15 VP7 protein lacked unique amino acid differences in the predicted neutralizing epitopes compared to the previously published swine RVB G12 strains, this report of RVB in Russian swine increases our epidemiological knowledge on the global prevalence and genetic diversity of RVB. Full article
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Open AccessCorrection
Correction: Kauppinen, A.; Miettinen, I.T. Persistence of Norovirus GII Genome in Drinking Water and Wastewater at Different Temperatures. Pathogens 2017, 6(4), 48
Pathogens 2018, 7(2), 45; doi:10.3390/pathogens7020045 (registering DOI) -
Open AccessArticle
Whole Genome Classification and Phylogenetic Analyses of Rotavirus B strains from the United States
Pathogens 2018, 7(2), 44; doi:10.3390/pathogens7020044 -
Abstract
Rotaviruses (RVs) are a major etiological agent of acute viral gastroenteritis in humans and young animals, with rotavirus B (RVB) often detected in suckling and weaned pigs. Group A rotavirus classification is currently based on the two outer capsid proteins, VP7 and VP4,
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Rotaviruses (RVs) are a major etiological agent of acute viral gastroenteritis in humans and young animals, with rotavirus B (RVB) often detected in suckling and weaned pigs. Group A rotavirus classification is currently based on the two outer capsid proteins, VP7 and VP4, and the middle layer protein, VP6. Using RVB strains generated in this study and reference sequences from GenBank, pairwise identity frequency graphs and phylogenetic trees were constructed for the eleven gene segments of RVB to estimate the nucleotide identity cutoff values for different genotypes and determine the genotype diversity per gene segment. Phylogenetic analysis of VP7, VP4, VP6, VP1–VP3, and NSP1–NSP5 identified 26G, 5P, 13I, 5R, 5C, 5M, 8A, 10N, 6T, 4E, and 7H genotypes, respectively. The analysis supports the previously proposed cutoff values for the VP7, VP6, NSP1, and NSP3 gene segments (80%, 81%, 76% and 78%, respectively) and suggests new cutoff values for the VP4, VP1, VP2, VP3, NSP2, NSP4, and NSP5 (80%, 78%, 79%, 77% 83%, 76%, and 79%, respectively). Reassortment events were detected between the porcine RVB strains from our study. This research describes the genome constellations for the complete genome of Group B rotaviruses in different host species. Full article
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Open AccessArticle
Multifocal Equine Influenza Outbreak with Vaccination Breakdown in Thoroughbred Racehorses
Pathogens 2018, 7(2), 43; doi:10.3390/pathogens7020043 -
Abstract
Equine influenza (EI) outbreaks occurred on 19 premises in Ireland during 2014. Disease affected thoroughbred (TB) and non-TB horses/ponies on a variety of premises including four racing yards. Initial clinical signs presented on 16 premises within a two-month period. Extensive field investigations were
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Equine influenza (EI) outbreaks occurred on 19 premises in Ireland during 2014. Disease affected thoroughbred (TB) and non-TB horses/ponies on a variety of premises including four racing yards. Initial clinical signs presented on 16 premises within a two-month period. Extensive field investigations were undertaken, and the diagnostic effectiveness of a TaqMan RT-PCR assay was demonstrated in regularly-vaccinated and sub-clinically-affected horses. Epidemiological data and repeat clinical samples were collected from 305 horses, of which 40% were reported as clinically affected, 39% were identified as confirmed cases and 11% were sub-clinically affected. Multivariable analysis demonstrated a significant association between clinical signs and age, vaccination status and number of vaccine doses received. Vaccine breakdown was identified in 31% of horses with up to date vaccination records. This included 27 horses in four different racing yards. Genetic and antigenic analysis identified causal viruses as belonging to Clade 2 of the Florida sublineage (FCL2). At the time of this study, no commercially available EI vaccine in Ireland had been updated in line with World Organisation for Animal Health (OIE) recommendations to include a FCL2 virus. The findings of this study highlight the potential ease with which EI can spread among partially immune equine populations. Full article
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Open AccessLetter
First Detection of the CTXM-15 Producing Escherichia coli O25-ST131 Pandemic Clone in Ecuador
Pathogens 2018, 7(2), 42; doi:10.3390/pathogens7020042 -
Abstract
Our aim was identify of the pandemic B2-ST131 Escherichia coli clone by to the Institute Pasteur and Achtman scheme, and investigate the resistance profile phenotypic-genotypic, with identification of class 1 integron. Of thirty-five ESBL-producing isolates recovered of patients with diagnosis of urinary tract
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Our aim was identify of the pandemic B2-ST131 Escherichia coli clone by to the Institute Pasteur and Achtman scheme, and investigate the resistance profile phenotypic-genotypic, with identification of class 1 integron. Of thirty-five ESBL-producing isolates recovered of patients with diagnosis of urinary tract infections (UTI), six E. coli strains serotype O25 were identified with resistance antimicrobial to several groups of antibiotics such as broad-spectrum cephalosporins, fluoroquinolones and aminoglycosides, harboring blaSHV, blaCTX-M genes in all isolates and blaTEM in two isolates. Sequencing of blaCTX-M revealed CTX-M-15 in all strains. The PMQR aac(6´)-Ib-cr and qnrB19 genes were presented in five and four isolates respectively, AMEs genes aac(6´)-Ib and aac(3)-IIa were presented in strain amikacin-gentamicin-resistant. Sequencing of the variable regions of the class 1 integron revealed dfrA and aadA genes cassette. The analysis of multilocus sequence typing (MLST) confirms the presence of the pandemic B2-ST131 E. coli clone by Achtman scheme in all ST43 isolates obtained by of the Institute Pasteur scheme. The results presented herein, reveal the presence of B2-ST131 E. coli clone in Ecuador, disseminated in hospitals and community settings. Full article
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Open AccessArticle
Association and Expression of Virulence from Plasmids of the Group B Strain in Pseudomonas syringae pv. eriobotryae
Pathogens 2018, 7(2), 41; doi:10.3390/pathogens7020041 -
Abstract
Pseudomonas syringae pv. eriobotryae causes serious stem canker in loquat (Eriobotrya japonica) trees. This study was conducted to determine whether plasmids are involved with its virulence. The strain NAE89, which belonged to the B group, harbored two plasmids at approximately 6.2
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Pseudomonas syringae pv. eriobotryae causes serious stem canker in loquat (Eriobotrya japonica) trees. This study was conducted to determine whether plasmids are involved with its virulence. The strain NAE89, which belonged to the B group, harbored two plasmids at approximately 6.2 and 50 Mdal that caused stem canker and halo leaf spots on loquat plants. Following digestion with BamHI and ligation into the BamHI cloning site of the broad range host cosmid pLAFR3, four DNA fragments at 3.8, 6.6, 12.3, and 22.8 kb were generated. Although the plasmid-encoded virulence gene psvA was undigested with the BamHI, the halo leaf spot gene may be adjacent to the psvA gene was digested. A pLAFR3 cosmid clone was introduced into the non-pathogenic PE0 and NAE89-1 strains by triparental matings and the pathogenicity was recovered. As a result, the pLAFR3 cosmid clone was introduced into the largest size DNA fragment of 22.8 kb and determined to be the causal agent of canker on the stem of the loquat. This study revealed that the psvA gene, previously found in the 50 Mdal plasmid, was also observed in the 22.8 kb DNA fragment. Full article
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Open AccessReview
The Microenvironment in Epstein–Barr Virus-Associated Malignancies
Pathogens 2018, 7(2), 40; doi:10.3390/pathogens7020040 -
Abstract
The Epstein–Barr virus (EBV) can cause a wide variety of cancers upon infection of different cell types and induces a highly variable composition of the tumor microenvironment (TME). This TME consists of both innate and adaptive immune cells and is not merely an
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The Epstein–Barr virus (EBV) can cause a wide variety of cancers upon infection of different cell types and induces a highly variable composition of the tumor microenvironment (TME). This TME consists of both innate and adaptive immune cells and is not merely an aspecific reaction to the tumor cells. In fact, latent EBV-infected tumor cells utilize several specific mechanisms to form and shape the TME to their own benefit. These mechanisms have been studied largely in the context of EBV+ Hodgkin lymphoma, undifferentiated nasopharyngeal carcinoma, and EBV+ gastric cancer. This review describes the composition, immune escape mechanisms, and tumor cell promoting properties of the TME in these three malignancies. Mechanisms of susceptibility which regularly involve genes related to immune system function are also discussed, as only a small proportion of EBV-infected individuals develops an EBV-associated malignancy. Full article
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Open AccessArticle
Cerebrospinal Fluid Concentrations of Biogenic Amines: Potential Biomarkers for Diagnosis of Bacterial and Viral Meningitis
Pathogens 2018, 7(2), 39; doi:10.3390/pathogens7020039 -
Abstract
Catecholamine and serotonin are biogenic amines (BAs) that serve as neurotransmitters and play an important role in the regulation of cardinal functions that are mainly altered during central nervous system (CNS) infections. A total 92 samples of cerebrospinal fluid (CSF) were classified into
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Catecholamine and serotonin are biogenic amines (BAs) that serve as neurotransmitters and play an important role in the regulation of cardinal functions that are mainly altered during central nervous system (CNS) infections. A total 92 samples of cerebrospinal fluid (CSF) were classified into 4 groups based on their etiology. In these samples, BAs/neurotransmitters i.e., dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) were detected and quantified by high performance liquid chromatography with electrochemical detection (HPLC-EC) to determine the neurophysiology of the CNS infections by bacteria (Listeria monocytogenes (Lm) and Neisseria meningitidis (Nm)) and herpes simplex virus (HSV). CSF concentration of DA, DOPAC, HVA, and 5HIAA were found significantly elevated in all test cohorts. Present study highlights that the analysis of BAs is pivotal for the early diagnosis of bacterial and viral meningitis. In addition, coinfections of varied etiology can also be diagnosed by their quantification. Thus, BAs can serve as potential biomarkers of these CNS infections. Full article
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Open AccessArticle
Presence of Human Enteric Viruses, Protozoa, and Indicators of Pathogens in the Bagmati River, Nepal
Pathogens 2018, 7(2), 38; doi:10.3390/pathogens7020038 -
Abstract
Quantification of waterborne pathogens in water sources is essential for alerting the community about health hazards. This study determined the presence of human enteric viruses and protozoa in the Bagmati River, Nepal, and detected fecal indicator bacteria (total coliforms, Escherichia coli, and
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Quantification of waterborne pathogens in water sources is essential for alerting the community about health hazards. This study determined the presence of human enteric viruses and protozoa in the Bagmati River, Nepal, and detected fecal indicator bacteria (total coliforms, Escherichia coli, and Enterococcus spp.), human-fecal markers (human Bacteroidales and JC and BK polyomaviruses), and index viruses (tobacco mosaic virus and pepper mild mottle virus). During a one-year period between October 2015 and September 2016, a total of 18 surface water samples were collected periodically from three sites along the river. Using quantitative polymerase chain reaction, all eight types of human enteric viruses tested—including adenoviruses, noroviruses, and enteroviruses, were detected frequently at the midstream and downstream sites, with concentrations of 4.4–8.3 log copies/L. Enteroviruses and saliviruses were the most frequently detected enteric viruses, which were present in 72% (13/18) of the tested samples. Giardia spp. were detected by fluorescence microscopy in 78% (14/18) of the samples, with a lower detection ratio at the upstream site. Cryptosporidium spp. were detected only at the midstream and downstream sites, with a positive ratio of 39% (7/18). The high concentrations of enteric viruses suggest that the midstream and downstream regions are heavily contaminated with human feces and that there are alarming possibilities of waterborne diseases. The concentrations of enteric viruses were significantly higher in the dry season than the wet season (p < 0.05). There was a significant positive correlation between the concentrations of human enteric viruses and the tested indicators for the presence of pathogens (IPP) (p < 0.05), suggesting that these IPP can be used to estimate the presence of enteric viruses in the Bagmati River water. Full article
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Open AccessFeature PaperBrief Report
Identification and In Silico Characterization of a Genetically Distinct Avian Rotavirus D Capsid Gene, VP7
Pathogens 2018, 7(2), 37; doi:10.3390/pathogens7020037 -
Abstract
Rotavirus D (RV-D) is gaining importance as a cause of gastroenteritis and runting and stunting syndrome (RSS) in poultry. To date, information is scarce on the molecular analysis of RV-D isolates worldwide. In this study, the VP7 gene, a major constituent of outer
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Rotavirus D (RV-D) is gaining importance as a cause of gastroenteritis and runting and stunting syndrome (RSS) in poultry. To date, information is scarce on the molecular analysis of RV-D isolates worldwide. In this study, the VP7 gene, a major constituent of outer capsid structural protein, from a RV-D isolate (UKD48) obtained from Uttarakhand state was analyzed. Phylogenetically, the RV-D isolate was found to be closely related to a South Korean strain, and the nucleotide percent identity varied from 80.4–84.2% with other RV-D strains available globally. Furthermore, domain investigation within 21 aligned amino acid sequences of the VP7 gene affirmed that this gene has several domains: a conserved glycosylation site (N–I–T) having an important role in protein folding; a N-terminal signal peptide (“ITG”) for endoplasmic reticulum retention; and two hydrophobic sites for elucidating transmembrane portions, antigenic structures, and so forth. The findings suggest that the VP7 gene of the Indian RV-D isolate is genetically distinct from those of other avian RV-Ds. Although biological evidence is still needed to prove the functional characteristics of these domains in outer capsid structural proteins, the present study adds new knowledge and derives the need for further investigation. Full article
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Open AccessReview
The Uptake and Metabolism of Amino Acids, and Their Unique Role in the Biology of Pathogenic Trypanosomatids
Pathogens 2018, 7(2), 36; doi:10.3390/pathogens7020036 -
Abstract
Trypanosoma brucei, as well as Trypanosoma cruzi and more than 20 species of the genus Leishmania, form a group of flagellated protists that threaten human health. These organisms are transmitted by insects that, together with mammals, are their natural hosts. This
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Trypanosoma brucei, as well as Trypanosoma cruzi and more than 20 species of the genus Leishmania, form a group of flagellated protists that threaten human health. These organisms are transmitted by insects that, together with mammals, are their natural hosts. This implies that during their life cycles each of them faces environments with different physical, chemical, biochemical, and biological characteristics. In this work we review how amino acids are obtained from such environments, how they are metabolized, and how they and some of their intermediate metabolites are used as a survival toolbox to cope with the different conditions in which these parasites should establish the infections in the insects and mammalian hosts. Full article
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Open AccessArticle
Influence of Intestinal Microbiota Transplantation and NleH Expression on Citrobacter rodentium Colonization of Mice
Pathogens 2018, 7(2), 35; doi:10.3390/pathogens7020035 -
Abstract
The intestinal microbiota plays an important role in regulating host resistance to enteric pathogens. The relative abundance of the microbiota is dependent upon both genetic and environmental factors. The attaching and effacing pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter
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The intestinal microbiota plays an important role in regulating host resistance to enteric pathogens. The relative abundance of the microbiota is dependent upon both genetic and environmental factors. The attaching and effacing pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter rodentium cause diarrheal disease and translocate type III secretion system effector proteins into host cells to inhibit pro-inflammatory host responses. Here we determined the influence of both the intestinal microbiota and the expression of the C. rodentium NleH effector on C. rodentium colonization in different mouse models. We performed fecal transplantation experiments between C57BL/6J and C57BL/10ScNJ mice and found that such microbiota transfers altered both the host resistance to C. rodentium infection as well as the benefit or detriment of expressing NleH to C. rodentium intestinal colonization. Full article
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Open AccessArticle
Effect of Early-Life Treatment of Piglets with Long-Acting Ceftiofur on Colonization of Streptococcus suis Serotype 7 and Elicitation of Specific Humoral Immunity in a Farm Dealing with Streptococcal Diseases
Pathogens 2018, 7(2), 34; doi:10.3390/pathogens7020034 -
Abstract
In newborn piglets treatment with long-acting ceftiofur is a common approach to reduce losses due to streptococcal diseases on farms, even if problems start after weaning. The purpose of this study was to examine the influence of a single early-life treatment on Streptococcus
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In newborn piglets treatment with long-acting ceftiofur is a common approach to reduce losses due to streptococcal diseases on farms, even if problems start after weaning. The purpose of this study was to examine the influence of a single early-life treatment on Streptococcus (S.) suis colonization, transmission, immunoreaction, and drug resistance over an observation period of 14 weeks. In a farm with a history of streptococcal disease and isolation of a S. suis cps 7 mrp+, arcA+ isolate from diseased piglets, half of each litter was treated with a long-acting ceftiofur on day 1. S. suis-isolates were profiled and serum samples were tested for opsonizing antibodies. Treated and untreated pigs did not differ according to average daily weight gains, S. suis-isolation rates and level of opsonizing antibodies. Although the invasive cps 7 strain was not detected in a single piglet over 14 weeks, all animals developed bactericidal activity. No resistance to ceftiofur, but resistance to tetracyclins (100%), and trimethoprim/sulfamethoxazole (53%) was shown. Our results indicate that early treatment with ceftiofur does not prevent colonization and transmission of S. suis or the induction of bactericidal humoral immunity in nursery and fattening pigs. The necessity of continuous usage should be reconsidered. Full article
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Open AccessArticle
Acidocalcisome-Mitochondrion Membrane Contact Sites in Trypanosoma brucei
Pathogens 2018, 7(2), 33; doi:10.3390/pathogens7020033 -
Abstract
Membrane contact sites are regions of close apposition between two organelles, typically less than 30 nanometers apart, that facilitate transfer of biomolecules. The presence of contact sites has been demonstrated in yeast, plants, and mammalian cells. Here, we investigated the presence of such
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Membrane contact sites are regions of close apposition between two organelles, typically less than 30 nanometers apart, that facilitate transfer of biomolecules. The presence of contact sites has been demonstrated in yeast, plants, and mammalian cells. Here, we investigated the presence of such contact sites in Trypanosoma brucei. In mammalian cells, endoplasmic reticulum-mitochondria contact sites facilitate mitochondrial uptake of Ca2+ released by the ER-located inositol 1,4,5-trisphosphate receptor (InsP3R). However, the InsP3R in trypanosomes localizes to acidocalcisomes, which serve as major Ca2+ stores in these parasites. In this work, we have used super-resolution structured illumination microscopy and electron microscopy to identify membrane contact sites that exist between acidocalcisomes and mitochondria. Furthermore, we have confirmed the close association of these organelles using proximity ligation assays. Characterization of these contact sites may be a necessary starting point towards unraveling the role of Ca2+ in regulating trypanosome bioenergetics. Full article
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Open AccessArticle
Variations in the Peritrophic Matrix Composition of Heparan Sulphate from the Tsetse Fly, Glossina morsitans morsitans
Pathogens 2018, 7(1), 32; doi:10.3390/pathogens7010032 -
Abstract
Tsetse flies are the principal insect vectors of African trypanosomes—sleeping sickness in humans and Nagana in cattle. One of the tsetse fly species, Glossina morsitans morsitans, is host to the parasite, Trypanosoma brucei, a major cause of African trypanosomiasis. Precise
[...] Read more.
Tsetse flies are the principal insect vectors of African trypanosomes—sleeping sickness in humans and Nagana in cattle. One of the tsetse fly species, Glossina morsitans morsitans, is host to the parasite, Trypanosoma brucei, a major cause of African trypanosomiasis. Precise details of the life cycle have yet to be established, but the parasite life cycle involves crossing the insect peritrophic matrix (PM). The PM consists of the polysaccharide chitin, several hundred proteins, and both glycosamino- and galactosaminoglycan (GAG) polysaccharides. Owing to the technical challenges of detecting small amounts of GAG polysaccharides, their conclusive identification and composition have not been possible until now. Following removal of PMs from the insects and the application of heparinases (bacterial lyase enzymes that are specific for heparan sulphate (HS) GAG polysaccharides), dot blots with a HS-specific antibody showed heparan sulphate proteoglycans (HSPGs) to be present, consistent with Glossina morsitans morsitans genome analysis, as well as the likely expression of the HSPGs syndecan and perlecan. Exhaustive HS digestion with heparinases, fluorescent labeling of the resulting disaccharides with BODIPY fluorophore, and separation by strong anion exchange chromatography then demonstrated the presence of HS for the first time and provided the disaccharide composition. There were no significant differences in the type of disaccharide species present between genders or between ages (24 vs. 48 h post emergence), although the HS from female flies was more heavily sulphated overall. Significant differences, which may relate to differences in infection between genders or ages, were evident, however, in overall levels of 2-O-sulphation between sexes and, for females, between 24 and 48 h post-emergence, implying a change in expression or activity for the 2-O-sulphotransferase enzyme. The presence of significant quantities of disaccharides containing the monosaccharide GlcNAc6S contrasts with previous findings in Drosophila melanogaster and suggests subtle differences in HS fine structure between species of the Diptera. Full article
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Open AccessFeature PaperReview
The Cooperative Functions of the EBNA3 Proteins Are Central to EBV Persistence and Latency
Pathogens 2018, 7(1), 31; doi:10.3390/pathogens7010031 -
Abstract
The Epstein–Barr nuclear antigen 3 (EBNA3) family of proteins, comprising EBNA3A, EBNA3B, and EBNA3C, play pivotal roles in the asymptomatic persistence and life-long latency of Epstein–Barr virus (EBV) in the worldwide human population. EBNA3-mediated transcriptional reprogramming of numerous host cell genes promotes in
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The Epstein–Barr nuclear antigen 3 (EBNA3) family of proteins, comprising EBNA3A, EBNA3B, and EBNA3C, play pivotal roles in the asymptomatic persistence and life-long latency of Epstein–Barr virus (EBV) in the worldwide human population. EBNA3-mediated transcriptional reprogramming of numerous host cell genes promotes in vitro B cell transformation and EBV persistence in vivo. Despite structural and sequence similarities, and evidence of substantial cooperative activity between the EBNA3 proteins, they perform quite different, often opposing functions. Both EBNA3A and EBNA3C are involved in the repression of important tumour suppressive pathways and are considered oncogenic. In contrast, EBNA3B exhibits tumour suppressive functions. This review focuses on how the EBNA3 proteins achieve the delicate balance required to support EBV persistence and latency, with emphasis on the contribution of the Allday laboratory to the field of EBNA3 biology. Full article
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Open AccessReview
Navigating the Host Cell Response during Entry into Sites of Latent Cytomegalovirus Infection
Pathogens 2018, 7(1), 30; doi:10.3390/pathogens7010030 -
Abstract
The host cell represents a hostile environment that viruses must counter in order to establish infection. Human cytomegalovirus (HCMV) is no different and encodes a multitude of functions aimed at disabling, re-directing or hijacking cellular functions to promulgate infection. However, during the very
[...] Read more.
The host cell represents a hostile environment that viruses must counter in order to establish infection. Human cytomegalovirus (HCMV) is no different and encodes a multitude of functions aimed at disabling, re-directing or hijacking cellular functions to promulgate infection. However, during the very early stages of infection the virus relies on the outcome of interactions between virion components, cell surface receptors and host signalling pathways to promote an environment that supports infection. In the context of latent infection—where the virus establishes an infection in an absence of many gene products specific for lytic infection—these initial interactions are crucial events. In this review, we will discuss key host responses triggered by viral infection and how, in turn, the virus ameliorates the impact on the establishment of non-lytic infections of cells. We will focus on strategies to evade intrinsic antiviral and innate immune responses and consider their impact on viral infection. Finally, we will consider the hypothesis that the very early events upon viral infection are important for dictating the outcome of infection and consider the possibility that events that occur during entry into non-permissive cells are unique and thus contribute to the establishment of latency. Full article
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Open AccessReview
Control of Bovine Viral Diarrhea
Pathogens 2018, 7(1), 29; doi:10.3390/pathogens7010029 -
Abstract
Bovine viral diarrhea (BVD) is one of the most important infectious diseases of cattle with respect to animal health and economic impact. Its stealthy nature, prolonged transient infections, and the presence of persistently infected (PI) animals as efficient reservoirs were responsible for its
[...] Read more.
Bovine viral diarrhea (BVD) is one of the most important infectious diseases of cattle with respect to animal health and economic impact. Its stealthy nature, prolonged transient infections, and the presence of persistently infected (PI) animals as efficient reservoirs were responsible for its ubiquitous presence in cattle populations worldwide. Whereas it was initially thought that the infection was impossible to control, effective systematic control strategies have emerged over the last 25 years. The common denominators of all successful control programs were systematic control, removal of PI animals, movement controls for infected herds, strict biosecurity, and surveillance. Scandinavian countries, Austria, and Switzerland successfully implemented these control programs without using vaccination. Vaccination as an optional and additional control tool was used by e.g., Germany, Belgium, Ireland, and Scotland. The economic benefits of BVD control programs had been assessed in different studies. Full article
Open AccessFeature PaperReview
EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts
Pathogens 2018, 7(1), 28; doi:10.3390/pathogens7010028 -
Abstract
The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders
[...] Read more.
The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification. In this article, we review the definitions, morphology, pathogenesis, and evolving concepts of the various EBV-associated disorders including EBV+ diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), EBV+ mucocutaneous ulcer, DLBCL associated with chronic inflammation, fibrin-associated DLBCL, lymphomatoid granulomatosis, the EBV+ T and NK-cell LPD of childhood, aggressive NK leukaemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity of primary EBV+ nodal T- or NK-cell lymphoma. The current knowledge regarding the pathogenesis of B-cell lymphomas that can be EBV-associated including Burkitt lymphoma, plasmablastic lymphoma and classic Hodgkin lymphoma will be also explored. Full article
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Open AccessFeature PaperReview
Pharmacological Agents Targeting the Cellular Prion Protein
Pathogens 2018, 7(1), 27; doi:10.3390/pathogens7010027 -
Abstract
Prion diseases are associated with the conversion of the cellular prion protein (PrPC), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrPSc) that accumulates
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Prion diseases are associated with the conversion of the cellular prion protein (PrPC), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrPSc) that accumulates in brain tissues of affected individuals. PrPSc is a self-catalytic protein assembly capable of recruiting native conformers of PrPC, and causing their rearrangement into new PrPSc molecules. Several previous attempts to identify therapeutic agents against prion diseases have targeted PrPSc, and a number of compounds have shown potent anti-prion effects in experimental models. Unfortunately, so far, none of these molecules has successfully been translated into effective therapies for prion diseases. Moreover, mounting evidence suggests that PrPSc might be a difficult pharmacological target because of its poorly defined structure, heterogeneous composition, and ability to generate different structural conformers (known as prion strains) that can elude pharmacological intervention. In the last decade, a less intuitive strategy to overcome all these problems has emerged: targeting PrPC, the common substrate of any prion strain replication. This alternative approach possesses several technical and theoretical advantages, including the possibility of providing therapeutic effects also for other neurodegenerative disorders, based on recent observations indicating a role for PrPC in delivering neurotoxic signals of different misfolded proteins. Here, we provide an overview of compounds claimed to exert anti-prion effects by directly binding to PrPC, discussing pharmacological properties and therapeutic potentials of each chemical class. Full article
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