| Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication. | Kumar M, Bandi S, Cheng K, Gupta S. Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication. Xenotransplantation 2011; 18: 380-389. © 2011 John Wiley & Sons A/S. Abstract: Background: Studies of natural hepatitis B virus infection must be restricted to humans or primates due to viral species-specificity. Alternative hepadnavirus animal models, e.g., woodchuck hepatitis virus in captive woodchucks, are not convenient, whi ... | 2011 | 22168144 |
| efficient reprogramming of human cord blood cd34(+) cells into induced pluripotent stem cells with oct4 and sox2 alone. | the reprogramming of cord blood (cb) cells into induced pluripotent stem cells (ipscs) has potential applications in regenerative medicine by converting cb banks into ipsc banks for allogeneic cell replacement therapy. therefore, further investigation into novel approaches for efficient reprogramming is necessary. here, we show that the lentiviral expression of oct4 together with sox2 (os) driven by a strong spleen focus-forming virus (sffv) promoter in a single vector can convert 2% of cb cd34( ... | 2011 | 22108860 |
| the expression of pd-1 ligands and their involvement in regulation of t cell functions in acute and chronic woodchuck hepatitis virus infection. | the programmed cell death 1 (pd-1)/programmed death-1 ligand 1 (pd-l1) system may play a role in the negative regulation of t cell functions in hepatitis b virus (hbv) infection. thus, it is important to study its role in the widely used animal model for hbv infection of woodchucks with woodchuck hepatitis virus (whv). | 2011 | 22022563 |
| hibernation does not reduce cortical bone density, area or second moments of inertia in woodchucks (marmota monax). | long periods of inactivity in most mammals result in bone loss that may not be completely recoverable during an individual's lifetime regardless of future activity. prolonged inactivity is normal during hibernation, but it remains uncertain whether hibernating mammals suffer decreased bone properties after hibernation that affects survival. we test the hypothesis that relative cortical area (c(a) ), apparent density, bone area fraction (b.ar/t.ar), and moments of inertia do not differ between mu ... | 2012 | 22234945 |
| anti-angiogenic therapy renders large tumors vulnerable to immunotherapy via reducing immunosuppression in the tumor microenvironment. | we have recently demonstrated that a 4-in-1 gene therapy strategy that contains two anti-angiogenic genes [endostatin and pigment epithelium-derived factor] and two cytokine genes [granulocyte macrophage colony-stimulating factor and interleukin 12] has a considerable antitumor effect on large tumors in a woodchuck hepatoma model. the current study further investigates the underlying mechanisms for the antitumor effect observed by using small rodent models. we found that immunotherapy alone incr ... | 2012 | 22266191 |
| the fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis. | genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. we have developed an in utero model that demonstrates that hepatocellular carcinoma (hcc) development is restricted to mice receiving nonprimate (np) lentiviral vectors (lv) and does not occur when a primate (p) lv is used regardless of woodchuck post-translation regulatory element (wpre) mutations to prevent truncated x gene expression. analysis of 839 nplv and 244 plv integrations in the live ... | 2012 | 23299800 |
| efficient lentiviral transduction of human mesenchymal stem cells that preserves proliferation and differentiation capabilities. | long-term lentiviral transduction of human mesenchymal stem cells (hmscs) greatly enhances the usefulness of these cells. however, such transduction currently requires the use of polybrene, which severely inhibits hmsc proliferation. in contrast, protamine sulfate at 100 μg/ml doubled transduction efficiencies without affecting proliferation or differentiation potential. expression levels improved 2.2-fold with the addition of a woodchuck hepatitis post-transcriptional regulatory element. furthe ... | 2012 | 23283550 |
| potential role of deer tick virus in powassan encephalitis cases in lyme disease-endemic areas of new york, u.s.a. | powassan virus, a member of the tick-borne encephalitis group of flaviviruses, encompasses 2 lineages with separate enzootic cycles. the prototype lineage of powassan virus (powv) is principally maintained between ixodes cookei ticks and the groundhog (marmota momax) or striped skunk (mephitis mephitis), whereas the deer tick virus (dtv) lineage is believed to be maintained between ixodes scapularis ticks and the white-footed mouse (peromyscus leucopus). we report 14 cases of powassan encephalit ... | 2013 | 24274334 |
| isolation of deer tick virus (powassan virus, lineage ii) from ixodes scapularis and detection of antibody in vertebrate hosts sampled in the hudson valley, new york state. | deer tick virus, dtv, is a genetically and ecologically distinct lineage of powassan virus (powv) also known as lineage ii powv. human incidence of pow encephalitis has increased in the last 15 years potentially due to the emergence of dtv, particularly in the hudson valley of new york state. we initiated an extensive sampling campaign to determine whether powv was extant throughout the hudson valley in tick vectors and/or vertebrate hosts. | 2013 | 24016533 |
| p. falciparum and p. vivax epitope-focused vlps elicit sterile immunity to blood stage infections. | in order to design p. falciparum preerythrocytic vaccine candidates, a library of circumsporozoite (cs) t and b cell epitopes displayed on the woodchuck hepatitis virus core antigen (whcag) vlp platform was produced. to test the protective efficacy of the whcag-cs vlps, hybrid cs p. berghei/p. falciparum (pb/pf) sporozoites were used to challenge immunized mice. vlps carrying 1 or 2 different cs repeat b cell epitopes and 3 vlps carrying different cs non-repeat b cell epitopes elicited high leve ... | 2015 | 25933001 |
| porcine synapsin 1: syn1 gene analysis and functional characterization of the promoter. | synapsin 1 (syn1) is a phosphoprotein involved in nerve signal transmission. the porcine syn1 promoter orthologue was cloned and characterized to provide a means of expressing a transgene specifically in neurons. the nucleotide sequence of the promoter displayed a high degree of conservation of elements responsible for neuron-specific expression. expression analysis of syn1 demonstrated presence of transcript during embryonic development. analysis of gfp expression in transgenic zebrafish embryo ... | 2013 | 24251104 |
| molecular characterization of woodchuck ifi16 and aim2 and their expression in woodchucks infected with woodchuck hepatitis virus (whv). | ifi16 and aim2 are important dna sensors in antiviral immunity. to characterize these two molecules in a woodchuck model, which is widely used to study hepatitis b virus (hbv) infection, we cloned and analyzed the complete coding sequences (cdss) of woodchuck ifi16 and aim2, and found that aim2 was highly conserved in mammals, whereas the degree of sequence identity between woodchuck ifi16 and its mammalian orthologues was low. ifi16 and ifn-β were upregulated following vacv ds 70 mer transfecti ... | 2016 | 27354260 |
| capture of syncytin-mar1, a fusogenic endogenous retroviral envelope gene involved in placentation in the rodentia squirrel-related clade. | syncytin genes are fusogenic envelope protein (env) genes of retroviral origin that have been captured for a function in placentation. within rodents, two such genes have previously been identified in the mouse-related clade, allowing a demonstration of their essential role via knockout mice. here, we searched for similar genes in a second major clade of the rodentia order, the squirrel-related clade, taking advantage of the complete sequencing of the ground squirrel ictidomys tridecemlineatus g ... | 2014 | 24789792 |
| origins and evolution of hepatitis b virus and hepatitis d virus. | members of the family hepadnaviridae fall into two subgroups: mammalian and avian. the detection of endogenous avian hepadnavirus dna integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. the nonprimate mammalian members of the hepadnaviridae include the woodchuck hepatitis virus (whv), the ground squirrel hepatitis virus, and arctic squirrel he ... | 2016 | 26729756 |
| design and evaluation of an edwardsiella tarda dna vaccine co-encoding antigenic and adjuvant peptide. | edwardsiella tarda is associated with edwardsiellosis in cultured fish, resulting in heavy losses in aquaculture. so far, different types of vaccine have been attempted against e. tarda. in this study, an optimized eukaryotic expression plasmid was developed and an optimized dna vaccine co-encoding antigenic and adjuvant peptide using a bicistronic expression system was designed. as a result, a modified plasmid harbored cytomegalovirus (cmv) promoter attached with r region of long terminal repea ... | 2016 | 27765700 |
| enhancing transgene expression from recombinant aav8 vectors in different tissues using woodchuck hepatitis virus post-transcriptional regulatory element. | adeno-associated virus (aav) vectors have been utilized extensively in gene therapy and gene function studies, as strong transgene expression is a prerequisite for positive outcomes. aav8 was reported as the most efficient aav serotype for transduction of the liver, brain and muscle compared with other serotypes. however, aav8-mediated transduction of human hepatocytes is rather poor with approximately 20-fold lower efficiency compared with that of mouse hepatocytes. therefore, we applied the wo ... | 2016 | 27076785 |
| construction of recombinant baculovirus vaccines for newcastle disease virus and an assessment of their immunogenicity. | newcastle disease (nd) is a lethal avian infectious disease caused by newcastle disease virus (ndv) which poses a substantial threat to china's poultry industry. conventional live vaccines against ndv are available, but they can revert to virulent strains and do not protect against mutant strains of the virus. therefore, there is a critical unmet need for a novel vaccine that is safe, efficacious, and cost effective. here, we designed novel recombinant baculovirus vaccines expressing the ndv f o ... | 2016 | 27015979 |
| [construction of baculovirus vector with wpre regulatory element to express newcastle disease virus f gene in primary chicken embryo cells]. | to construct the recombinant baculovirus with mammaliancell-specific promoter and woodchuck hepatitis virus post-transcriptional regulatory element (wpre), to highly express newcastle disease virus (ndv) f gene in the primary chicken embryo cells. | 2014 | 25007659 |
| optimization of egfp expression using a modified baculovirus expression system. | the baculovirus gene expression system is an efficient and safe protein expression system, since baculoviruses cannot replicate in mammalian cells. in order to improve the transduction efficiency and increase the reporter gene expression levels delivered by baculoviruses, we tested in the baculovirus expression cassette the woodchuck hepatitis virus response element (wpre), and aav-derived inverted terminal repeats (itrs) and the truncated vesicular stomatitis virus g protein (vsv-ged). the resu ... | 2014 | 24445173 |
| [construction of baculovirus vector with cytomegaloviruse promoter to express egfp in primary chicken embryo cells]. | baculovirus is known as a safe vector candidate due to its non-replication in mammalian cells. the tropism to different cells and transduction efficiency can be improved by introducing cell-specific promoter, vsv-ged and different functional regulatory elements. the optimized pseudotyped recombinant baculovirus can express egfp gene in primary chicken cells, which provides us a new approach to develop engineered poultry vaccines. | 2013 | 24028061 |
| induction of hantaan virus-specific immune responses in c57bl/6 mice by immunization with a modified recombinant adenovirus containing the chimeric gene, gcs0.7. | hantavirus glycoprotein gc is one of the main components that contribute to the generation of humoral immune responses, while the nucleocapsid protein (np) is involved in cellular immune responses through the induction of antibody-dependent cytotoxic t cells. in this study, a chimeric gene, gcs0.7, which encodes a fusion protein containing gc and truncated np, was constructed as a candidate for hantaan virus (htnv) vaccine development. the chimeric gene was cloned into an adenoviral vector in co ... | 2013 | 23783439 |
| functional expression of rab escort protein 1 following aav2-mediated gene delivery in the retina of choroideremia mice and human cells ex vivo. | choroideremia (chm) is an x-linked retinal degeneration of photoreceptors, the retinal pigment epithelium (rpe) and choroid caused by loss of function mutations in the chm/rep1 gene that encodes rab escort protein 1. as a slowly progressing monogenic retinal degeneration with a clearly identifiable phenotype and a reliable diagnosis, chm is an ideal candidate for gene therapy. we developed a serotype 2 adeno-associated viral vector aav2/2-cba-rep1, which expresses rep1 under control of cmv-enhan ... | 2013 | 23756766 |
| generation of an optimized lentiviral vector encoding a high-expression factor viii transgene for gene therapy of hemophilia a. | we previously compared the expression of several human factor viii (fviii) transgene variants and demonstrated the superior expression properties of b domain-deleted porcine fviii. subsequently, a hybrid human/porcine fviii molecule (hp-fviii) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine fviii. the bioengineered construct then was used effectively to treat knockout mice with hemophilia a. in the current study, we focused on op ... | 2013 | 22996197 |
| long-term engraftment and angiogenic properties of lentivirally transduced adipose tissue-derived stromal cells. | human adipose tissue-derived stromal cells (adscs) are being evaluated for cardiovascular repair. we developed an ex vivo method for producing angiogenic adscs transduced with a self-inactivating lentiviral vector (lv) expressing the enhanced green fluorescence protein (egfp) from an internal cytomegalovirus (cmv) promoter to track these cells after in vivo engraftment. adscs from visceral adipose tissue were transduced using a lv incorporating the rous sarcoma virus (rsv) long terminal repeat ( ... | 2013 | 22492300 |
| lentivirus vector driven by polybiquitin c promoter without woodchuck posttranscriptional regulatory element and central polypurine tract generates low level and short-lived reporter gene expression. | lentivirus (lv) encoding woodchuck posttranscriptional regulatory element (wpre) and central polypurine tract (cppt) driven by cmv promoter have been proven to act synergistically to increase both transduction efficiency and gene expression. however, the inclusion of wpre and cppt in a lentiviral construct may pose safety risks when administered to human. a simple lentiviral construct driven by an alternative promoter with proven extended duration of gene expression without the two regulatory el ... | 2012 | 22366305 |
| present and future dna vaccines for chronic hepatitis b treatment. | with at least 240 million hepatitis b virus (hbv) carriers worldwide, being at a high risk of cirrhosis and hepatocellular carcinoma (hcc), chronic hepatitis b remains a major public health issue. because current antiviral treatments are only virostatic, there is an urgent need for the development of innovative anti-hbv strategies leading to the functional cure. in this context, dna-based vaccines appear as a promising approach. area covered: in this review, the authors summarize the pertinent f ... | 2017 | 27892722 |
| possible origins and evolution of the hepatitis b virus (hbv). | all members of the family hepadnaviridae are primarily viruses which contain double-stranded dna genomes that are replicated via reverse transcription of a pregenomic rna template. there are two subgroups within this family: mammalian and avian. the avian member's include the duck hepatitis b virus (dhbv), heron hepatitis b virus, ross goose hepatitis b virus, stork hepatitis b virus and the recently identified parrot hepatitis b virus. more recently, the detection of endogenous avian hepadnavir ... | 2013 | 24013024 |
| sulfamoylbenzamide derivatives inhibit the assembly of hepatitis b virus nucleocapsids. | chronic hepatitis b virus (hbv) infection, a serious public health problem leading to cirrhosis and hepatocellular carcinoma, is currently treated with either pegylated alpha interferon (pegifn-α) or one of the five nucleos(t)ide analogue viral dna polymerase inhibitors. however, neither pegifn-α nor nucleos(t)ide analogues are capable of reliably curing the viral infection. in order to develop novel antiviral drugs against hbv, we established a cell-based screening assay by using an immortalize ... | 2013 | 23576513 |
| a novel astrovirus species in the gut of yaks with diarrhoea in the qinghai–tibetan plateau, 2013. | the yak (bos grunniens) is an iconic symbol in the high-altitude region of the qinghai–tibetan plateau. diarrhoea is a common disease in yaks, resulting in major economic losses. to investigate the diversity of viral species, we reported the metagenomics-derived virome in a pooled faecal sample of 20 diarrhoeic yaks. the nine viruses found in the pooled diarrhoeic samples, in order of abundance of nucleic acid sequence, were influenza a virus, bovine viral diarrhoea virus (bvdv), rotavirus, ungu ... | 2015 | 26419604 |
| recombinant aav vectors for enhanced expression of authentic igg. | adeno-associated virus (aav) has become a vector of choice for the treatment of a variety of genetic diseases that require safe and long-term delivery of a missing protein. muscle-directed gene transfer for delivery of protective antibodies against aids viruses and other pathogens has been used experimentally in mice and monkeys. here we examined a number of variations to aav vector design for the ability to produce authentic immunoglobulin g (igg) molecules. expression of rhesus igg from a sing ... | 2016 | 27332822 |
| potential mechanisms of hepatitis b virus induced liver injury. | chronic active hepatitis (cah) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. the histological end points of cah are chronic inflammation, fibrosis and cirrhosis which are coupled with increased dna synthesis in cirrhotic vs healthy normal livers. the potential mechanism involved in cah includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). the severity ... | 2014 | 25253946 |
| low hepatitis b virus-specific t-cell response in males correlates with high regulatory t-cell numbers in murine models. | hepatitis b virus (hbv) infection shows significant gender-related differences in pathogenesis, disease progression, and development of hepatocellular carcinoma. the gender-associated differences in hbv replication and viral protein levels may be associated with distinct hbv-specific immune responses in the host. in the present study, we examined the impact of gender on hbv-specific immune responses in two different mouse models representing transient and persistent hepadnaviral infection; hydro ... | 2017 | 28295453 |
| prevention of liver tumor formation in woodchucks with established hepatocellular carcinoma by treatment with cationic liposome-dna complexes. | approximately 250 million people worldwide are chronically infected with hepatitis b virus (hbv) and more than half of the hepatocellular carcinoma (hcc) cases are attributed to this infection. as hcc has a high mortality rate, and current treatment options are remarkably limited, the development of new therapeutic treatment strategies is warranted. | 2017 | 28264666 |
| prec and c regions of woodchuck hepatitis virus facilitate persistent expression of surface antigen of chimeric whv-hbv virus in the hydrodynamic injection balb/c mouse model. | in the hydrodynamic injection (hi) balb/c mouse model with the overlength viral genome, we have found that woodchuck hepatitis virus (whv) could persist for a prolonged period of time (up to 45 weeks), while hepatitis b virus (hbv) was mostly cleared at week four. in this study, we constructed a series of chimeric genomes based on hbv and whv, in which the individual sequences of a 1.3-fold overlength hbv genome in pbs-hbv1.3 were replaced by their counterparts from whv. after hi with the whv-hb ... | 2017 | 28230775 |
| woodchuck sodium taurocholate cotransporting polypeptide supports low-level hepatitis b and d virus entry. | sodium taurocholate cotransporting polypeptide (ntcp) is the functional receptor for human hepatitis b virus (hbv) and its satellite hepatitis d virus (hdv). species barriers to hbv/hdv infection are mainly determined at entry level by variations in the sequences of particular ntcp orthologs. in this study, we sought to determine whether the ntcp ortholog in woodchuck (marmota monax), woodchuck ntcp (wntcp) supports viral infection. we found that wntcp is capable of supporting hbv/hdv infection ... | 2017 | 28213271 |
| measurement of antiviral effect and innate immune response during treatment of primary woodchuck hepatocytes. | an estimated 350 million people are chronically infected with hepatitis b virus (hbv), and over one million people die each year due to hbv-associated liver diseases, such as cirrhosis and liver cancer. current therapeutics for chronic hbv infection are limited to nucleos(t)ide analogs and interferon. these anti-hbv drugs in general reduce viral load and improve the long-term outcome of infection but very rarely lead to a cure. thus, new therapies for chronic hbv infection need to be developed b ... | 2017 | 27975326 |
| diverse activities of viral cis-acting rna regulatory elements revealed using multicolor, long-term, single-cell imaging. | cis-acting rna structural elements govern crucial aspects of viral gene expression. how these structures and other posttranscriptional signals affect rna trafficking and translation in the context of single cells is poorly understood. herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral rna regulatory control in individual cells. we apply this strategy to demonstrate differential mrna trafficking behaviors governed by rna elements derived ... | 2017 | 27903772 |
| transcriptome analysis and comparison of marmota monax and marmota himalayana. | the eastern woodchuck (marmota monax) is a classical animal model for studying hepatitis b virus (hbv) infection and hepatocellular carcinoma (hcc) in humans. recently, we found that marmota himalayana, an asian animal species closely related to marmota monax, is susceptible to woodchuck hepatitis virus (whv) infection and can be used as a new mammalian model for hbv infection. however, the lack of genomic sequence information of both marmota models strongly limited their application breadth and ... | 2016 | 27806133 |
| [the true story and advantages of the famous hepatitis b virus core particles: outlook 2016]. | this review article is a continuation of the paper "hepatitis b core particles as a universal display model: a structure-function basis for development" written by pumpens p. and grens e., ordered by professor lev kisselev and published in febs letters, 1999, 442, 1-6. the past 17 years have strengthened the paper's finding that the human hepatitis b virus core protein, along with other hepadnaviridae family member core proteins, is a mysterious, multifunctional protein. the core gene of the hep ... | 2016 | 27668597 |
| molecular cloning, characterization and expression analysis of tgf-β and receptor genes in the woodchuck model. | transforming growth factor beta (tgf-β) is an important cytokine with pleiotropic regulatory functions in the immune system and in the responses against viral infections. tgf-β acts on a variety of immune cells through the cell surface tgf-β receptor (university of duisburg-essentgfbr). the woodchuck has been used as a biomedical model for studies of obesity and energy balance, endocrine and metabolic function, cardiovascular, cerebrovascular and neoplastic disease. woodchucks infected with wood ... | 2016 | 27637515 |
| activating the innate immune response to counter chronic hepatitis b virus infection. | chronic infection with hepatitis b virus (hbv) is endemic to several populous parts of the world, where resulting complicating cirrhosis and hepatocellular carcinoma occur commonly. licensed drugs to treat the infection have limited curative efficacy, and development of therapies that eliminate all replication intermediates of hbv is a priority. areas covered: the recent demonstration that the activation of the innate immune response may eradicate hbv from infected hepatocytes has a promising th ... | 2016 | 27603796 |
| antiviral efficacy and host innate immunity associated with sb 9200 treatment in the woodchuck model of chronic hepatitis b. | sb 9200, an oral prodrug of the dinucleotide sb 9000, is being developed for the treatment of chronic hepatitis b virus (hbv) infection and represents a novel class of antivirals. sb 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (rig-i) and nucleotide-binding oligomerization domain-containing protein 2 (nod2) resulting in interferon (ifn) mediated antiviral immune responses in virus-infected cells. additionally, the binding of sb 9200 to these sensor prote ... | 2016 | 27552102 |
| molecular cloning, characterization and expression analysis of woodchuck retinoic acid-inducible gene i. | cytosolic retinoic acid-inducible gene i (rig-i) is an important innate immune rna sensor and can induce antiviral cytokines, e.g., interferon-β (ifn-β). innate immune response to hepatitis b virus (hbv) plays a pivotal role in viral clearance and persistence. however, knowledge of the role that rig-i plays in hbv infection is limited. the woodchuck is a valuable model for studying hbv infection. to characterize the molecular basis of woodchuck rig-i (wrig-i), we analyzed the complete coding seq ... | 2016 | 27376800 |
| characterization of metastatic tumor antigen 1 and its interaction with hepatitis b virus x protein in nf-κb signaling and tumor progression in a woodchuck hepatocellular carcinoma model. | the metastatic tumor antigen 1 (mta1) protein is associated with tumor invasiveness and poor prognosis in patients with hepatocellular carcinoma (hcc), particularly in those with hepatitis b virus (hbv)-related hcc. chronically woodchuck hepatitis virus (whv)-infected woodchuck is an ideal animal model for studying the pathogenesis of hbv-associated liver diseases, including hcc. to investigate the roles of mta1 in hbv-associated hepatocarcinogenesis in the woodchuck model, we cloned the woodchu ... | 2016 | 27323415 |
| hepatitis b virus nuclear export elements: rna stem-loop α and β, key parts of the hbv post-transcriptional regulatory element. | many viruses contain rna elements that modulate splicing and/or promote nuclear export of their rnas. the rnas of the major human pathogen, hepatitis b virus (hbv) contain a large (~600 bases) composite cis-acting 'post-transcriptional regulatory element' (pre). this element promotes expression from these naturally intronless transcripts. indeed, the related woodchuck hepadnavirus pre (wpre) is used to enhance expression in gene therapy and other expression vectors. these pre are likely to act t ... | 2016 | 27031749 |
| aic649 induces a bi-phasic treatment response in the woodchuck model of chronic hepatitis b. | aic649 has been shown to directly address the antigen presenting cell arm of the host immune defense leading to a regulated cytokine release and activation of t cell responses. in the present study we analyzed the antiviral efficacy of aic649 as well as its potential to induce functional cure in animal models for chronic hepatitis b. hepatitis b virus transgenic mice and chronically woodchuck hepatitis virus (whv) infected woodchucks were treated with aic649, respectively. in the mouse system ai ... | 2015 | 26656974 |
| asymptomatic hepadnaviral persistence and its consequences in the woodchuck model of occult hepatitis b virus infection. | woodchuck hepatitis virus (whv) is molecularly and pathogenically closely related to hepatitis b virus (hbv). both viruses display tropism towards hepatocytes and cells of the immune system and cause similar liver pathology, where acute hepatitis can progress to chronic hepatitis and to hepatocellular carcinoma (hcc). two forms of occult hepadnaviral persistence were identified in the woodchuck-whv model: secondary occult infection (soi) and primary occult infection (poi). soi occurs after resol ... | 2015 | 26623268 |
| combination therapy including cpg oligodeoxynucleotides and entecavir induces early viral response and enhanced inhibition of viral replication in a woodchuck model of chronic hepadnaviral infection. | cpg oligodeoxynucleotides (odns) stimulate immune cells via tlr9 and are potentially useful immunomodulators for the treatment of chronic viral infections. in the present study, different classes of cpgs were tested for their capacities for innate immune activation and antiviral activities in the woodchuck model. a class p cpg odn was found to stimulate interferon (ifn) production in woodchuck peripheral blood mononuclear cells (pbmcs) in vitro, and following subcutaneous administration in vivo, ... | 2016 | 26585244 |
| the woodchuck, a nonprimate model for immunopathogenesis and therapeutic immunomodulation in chronic hepatitis b virus infection. | the woodchuck hepatitis virus (whv) and its host, the eastern woodchuck, is a very valuable model system for hepatitis b virus infection. many aspects of whv replication and pathogenesis resemble acute and chronic hepatitis b infection in patients. since the establishment of immunological tools, woodchucks were used to develop new therapeutic vaccines and immunomodulatory approaches to treat chronic hepadnaviral infections. combination therapy of nucleos(t)ide analogs, with prime-boost vaccinati ... | 2015 | 26511761 |
| current status of immunomodulatory therapy in chronic hepatitis b, fifty years after discovery of the virus: search for the "magic bullet" to kill cccdna. | chronic hepatitis b (chb) is currently treated with ifn-α and nucleos(t)ide analogues, which have many clinical benefits, but there is no ultimate cure. the major problem consists in the persistence of cccdna in infected hepatocytes. because no antiviral drug has been evaluated which significantly reduces copies of cccdna, cytolytic and noncytolytic approaches are needed. effective virus-specific t- and b-cell responses remain crucial in eliminating cccdna-carrying hepatocytes and for the long-t ... | 2015 | 26476376 |
| intrahepatic transcriptional signature associated with response to interferon-α treatment in the woodchuck model of chronic hepatitis b. | recombinant interferon-alpha (ifn-α) is an approved therapy for chronic hepatitis b (chb), but the molecular basis of treatment response remains to be determined. the woodchuck model of chronic hepatitis b virus (hbv) infection displays many characteristics of human disease and has been extensively used to evaluate antiviral therapeutics. in this study, woodchucks with chronic woodchuck hepatitis virus (whv) infection were treated with recombinant woodchuck ifn-α (wifn-α) or placebo (n = 12/grou ... | 2015 | 26352406 |
| mouse models of hepatitis b virus pathogenesis. | the host range of hepatitis b virus (hbv) is limited to humans and chimpanzees. as discussed in the literature, numerous studies in humans and chimpanzees have generated a great deal of information on the mechanisms that cause viral clearance, viral persistence, and disease pathogenesis during acute or chronic hbv infection. relevant pathogenetic studies have also been performed in those few species representing natural hosts of hepadnaviruses that are related to hbv, such as the woodchuck hepat ... | 2015 | 26292984 |
| persistence of the recombinant genomes of woodchuck hepatitis virus in the mouse model. | hydrodynamic injection (hi) with a replication competent hepatitis b virus (hbv) genome may lead to transient or prolonged hbv replication in mice. however, the prolonged hbv persistence after hi depends on the specific backbone of the vector carrying hbv genome and the genetic background of the mouse strain. we asked whether a genetically closely related hepadnavirus, woodchuck hepatitis virus (whv), may maintain the gene expression and replication in the mouse liver after hi. interestingly, we ... | 2015 | 25942393 |
| animal models and the molecular biology of hepadnavirus infection. | australian antigen, the envelope protein of hepatitis b virus (hbv), was discovered in 1967 as a prevalent serum antigen in hepatitis b patients. early electron microscopy (em) studies showed that this antigen was present in 22-nm particles in patient sera, which were believed to be incomplete virus. complete virus, much less abundant than the 22-nm particles, was finally visualized in 1970. hbv was soon found to infect chimpanzees, gorillas, orangutans, gibbon apes, and, more recently, tree shr ... | 2015 | 25833941 |
| liver-directed gene therapy of chronic hepadnavirus infection using interferon alpha tethered to apolipoprotein a-i. | current hepatitis b virus (hbv) management is challenging as treatment with nucleos(t)ide analogues needs to be maintained indefinitely and because interferon (ifn)-α therapy is associated with considerable toxicity. previously, we showed that linking ifnα to apolipoprotein a-i generates a molecule (ia) with distinct antiviral and immunostimulatory activities which lacks the hematological toxicity of ifnα. | 2015 | 25772035 |
| animal models of chronic hepatitis delta virus infection host-virus immunologic interactions. | hepatitis delta virus (hdv) is a defective rna virus that has an absolute requirement for a virus belonging to the hepadnaviridae family like hepatitis b virus (hbv) for its replication and formation of new virions. hdv infection is usually associated with a worsening of hbv-induced liver pathogenesis, which leads to more frequent cirrhosis, increased risk of hepatocellular carcinoma (hcc), and fulminant hepatitis. importantly, no selective therapies are available for hdv infection. the mainstay ... | 2015 | 25686091 |
| woodchuck hepatitis virus core gene deletions and proliferative responses of peripheral blood mononuclear cells stimulated by an immunodominant epitope: a viral immune escape in the woodchuck model of chronic hepatitis b? | marmota monax and its natural infection by woodchuck hepatitis virus (whv) could be used as a predictive model for evaluating mechanisms of viral persistence during chronic hepatitis b virus (hbv) infection. the aim of this study was to investigate the presence of viral variants in the core gene of chronically whv-infected woodchucks that showed two different patterns of peripheral blood mononuclear cells' (pbmcs') responses after stimulation with a specific whv core peptide. sequences' analysis ... | 2015 | 25666197 |
| therapeutic vaccines in hbv: lessons from hcv. | currently, millions of people infected with hepatitis b virus (hbv) are committed to decades of treatment with anti-viral therapy to control viral replication. however, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. this has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing hbeag seroconversion--an end-point that has been associated with a decrease in the rates of ... | 2015 | 25573348 |
| sustained efficacy and seroconversion with the toll-like receptor 7 agonist gs-9620 in the woodchuck model of chronic hepatitis b. | new therapies for chronic hepatitis b (chb) are urgently needed since current treatments rarely lead to cure. we evaluated whether the oral small molecule toll-like receptor (tlr7) agonist gs-9620 could induce durable antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus (whv), a hepadnavirus closely related to human hepatitis b virus (hbv). | 2015 | 25559326 |
| therapeutic vaccination and immunomodulation in the treatment of chronic hepatitis b: preclinical studies in the woodchuck. | infection with hepatitis b virus (hbv) may lead to subclinical, acute or chronic hepatitis. in the prevaccination era, hbv infections were endemic due to frequent mother to child transmission in large regions of the world. however, there are still estimated 240 million chronic hbv carriers today and ca. 620,000 patients die per year due to hbv-related liver diseases. recommended treatment of chronic hepatitis b with interferon-α and/or nucleos(t)ide analogues does not lead to satisfactory result ... | 2015 | 25535101 |
| woodchuck hepatitis virus core antigen-based dna and protein vaccines induce qualitatively different immune responses that affect t cell recall responses and antiviral effects. | t helper type 1 (th1) immunity was considered to play a dominant role in viral clearance of hepadnaviral infection. however, pre-primed th2 type responses were able to efficiently control hepadnaviral infection in animal models. we investigated how pre-primed th1/2 responses control hepadnaviral replication using the newly established mouse models. dna (pwhcim, pctla-4-c) and protein vaccines based on the nucleocapsid protein (whcag) of woodchuck hepatitis virus (whv) primed specific immune resp ... | 2015 | 25462346 |
| superinfection with woodchuck hepatitis virus strain whvny of livers chronically infected with strain whv7. | the determinants of the maintenance of chronic hepadnaviral infection are yet to be fully understood. a long-standing unresolved argument in the hepatitis b virus (hbv) research field suggests that during chronic hepadnaviral infection, cell-to-cell spread of hepadnavirus is at least very inefficient (if it occurs at all), virus superinfection is an unlikely event, and chronic hepadnavirus infection can be maintained exclusively via division of infected hepatocytes in the absence of virus spread ... | 2015 | 25320318 |
| structurally similar woodchuck and human hepadnavirus core proteins have distinctly different temperature dependences of assembly. | woodchuck hepatitis virus (whv), a close relative of human hepatitis b virus (hbv), has been a key model for disease progression and clinical studies. sequences of the assembly domain of whv and hbv core proteins (wcp149 and hcp149, respectively) have 65% identity, suggesting similar assembly behaviors. we report a cryo-electron microscopy (cryo-em) structure of the whv capsid at nanometer resolution and characterization of wcp149 assembly. at this resolution, the t=4 capsid structures of whv an ... | 2014 | 25253350 |
| primary seronegative but molecularly evident hepadnaviral infection engages liver and induces hepatocarcinoma in the woodchuck model of hepatitis b. | hepadnavirus at very low doses establishes in woodchucks asymptomatic, serologically undetectable but molecularly evident persistent infection. this primary occult infection (poi) preferentially engages the immune system and initiates virus-specific t cell response in the absence of antiviral antibody induction. the current study aimed to determine whether poi with time may culminate in serologically identifiable infection and hepatitis, and what are, if any, its pathological consequences. juven ... | 2014 | 25165821 |
| advances and challenges in the development of therapeutic dna vaccines against hepatitis b virus infection. | despite the existence of an effective prophylactic vaccine, chronic hepatitis b virus (hbv) infection remains a major public health problem. because very weak and functionally impaired virus-specific immune responses play a key role in the persistence of hbv infection, the stimulation of these responses appears to be of particular importance for virus clearance. in this regard dna-based vaccination has emerged as novel, promising therapeutic approach for chronic hepatitis b. this review provides ... | 2014 | 24828255 |
| nucleoside analogues alone or combined with vaccination prevent hepadnavirus viremia and induce protective immunity: alternative strategy for hepatitis b virus post-exposure prophylaxis. | the current strategies for hepatitis b virus (hbv) post-exposure prophylaxis (pep) are not generally available in remote and rural areas of developing countries and/or carry potential risks for infection with blood-borne transmitted pathogens. nucleotide analogues (nas) are successfully used for human immunodeficiency virus pep, and maybe effective for hbv pep. in this study, we tested the na-based strategies for hbv pep using the chinese woodchuck model. | 2014 | 24583157 |
| enhancing virus-specific immunity in vivo by combining therapeutic vaccination and pd-l1 blockade in chronic hepadnaviral infection. | hepatitis b virus (hbv) persistence is facilitated by exhaustion of cd8 t cells that express the inhibitory receptor programmed cell death-1 (pd-1). improvement of the hbv-specific t cell function has been obtained in vitro by inhibiting the pd-1/pd-ligand 1 (pd-l1) interaction. in this study, we examined whether in vivo blockade of the pd-1 pathway enhances virus-specific t cell immunity and leads to the resolution of chronic hepadnaviral infection in the woodchuck model. the woodchuck pd-1 was ... | 2014 | 24391505 |
| variability in the precore and core promoter region of the hepatitis b virus genome. | there is increasing evidence that hepatitis b virus (hbv) infections with different genotypes and subgenotypes differ in response to treatment and long-term prognosis. the differences emerge from variability within the genomes that leads to structural deviations at the pregenomic level and to changes at the translational level. naturally occurring hbv strains covering the four major genotypes a-d were obtained from 393 patients and part of the genome was amplified using polymerase chain reaction ... | 2014 | 24249691 |
| unraveling the complexity of hepatitis b virus: from molecular understanding to therapeutic strategy in 50 years. | hepatitis b virus (hbv) is a well-known hepadnavirus with a double-stranded circular dna genome. although hbv was first described approximately 50 years ago, the precise mechanisms of hbv infection and effective therapeutic strategies remain unclear. here, we focus on summarizing the complicated mechanisms of hbv replication and infection, as well as genomic factors and epigenetic regulation. additionally, we discuss in vivo models of hbv, as well as diagnosis, prevention and therapeutic drugs f ... | 2013 | 23819994 |
| combination of dna prime--adenovirus boost immunization with entecavir elicits sustained control of chronic hepatitis b in the woodchuck model. | a potent therapeutic t-cell vaccine may be an alternative treatment of chronic hepatitis b virus (hbv) infection. previously, we developed a dna prime-adenovirus (adv) boost vaccination protocol that could elicit strong and specific cd8+ t-cell responses to woodchuck hepatitis virus (whv) core antigen (whcag) in mice. in the present study, we first examined whether this new prime-boost immunization could induce whcag-specific t-cell responses and effectively control whv replication in the whv-tr ... | 2013 | 23785279 |
| molecular characterization of woodchuck cd4 (wcd4) and production of a depletion monoclonal antibody against wcd4. | cd4 t cells play an important role in the immune response against hepatitis b virus (hbv) infection. woodchucks represent an excellent animal model to study hbv infection. in this study, we characterized the cdna sequence of woodchuck cd4 (wcd4). the deduced wcd4 protein has four extracellular immunoglobulin-like domains comparable to the other mammalian cd4 molecules. the important extracellular cysteine residues and the intracellular tyrosine protein kinase-binding site of wcd4 are also conser ... | 2013 | 23685260 |
| prime/boost immunization with dna and adenoviral vectors protects from hepatitis d virus (hdv) infection after simultaneous infection with hdv and woodchuck hepatitis virus. | hepatitis d virus (hdv) superinfection of hepatitis b virus (hbv) carriers causes severe liver disease and a high rate of chronicity. therefore, a vaccine protecting hbv carriers from hdv superinfection is needed. to protect from hdv infection an induction of virus-specific t cells is required, as antibodies to the two proteins of hdv, p24 and p27, do not neutralize the hbv-derived envelope of hdv. in mice, hdv-specific cd8(+) and cd4(+) t cell responses were induced by a dna vaccine expressing ... | 2013 | 23637419 |
| expression of matrix metalloproteinases and their inhibitors in the woodchuck model of hepatocellular carcinoma. | matrix metalloproteinases (mmps) play a central role in tumor invasion and metastasis. increased expression of mmps occurs during development of hepatocellular carcinoma (hcc) in humans following infection with hepatitis b virus (hbv). woodchucks are used as an animal model for hepadnavirus-induced hcc. all woodchucks infected chronically with woodchuck hepatitis virus (whv), a virus that is closely related to hbv, develop hcc. in the present study mmps and related molecules were investigated in ... | 2013 | 23595580 |
| deregulation of epigenetic mechanisms by the hepatitis b virus x protein in hepatocarcinogenesis. | this review focuses on the significance of deregulation of epigenetic mechanisms by the hepatitis b virus (hbv) x protein in hepatocarcinogenesis and hbv replication. epigenetic mechanisms, dna methylation, and specific histone modifications, e.g., trimethylation of h3 on lysine-27 or lysine-4, maintain 'cellular memory' by silencing expression of lineage-inducing factors in stem cells and conversely, of pluripotency factors in differentiated cells. the x protein has been reported to induce expr ... | 2013 | 23507839 |
| molecular biology of the hepatitis b virus for clinicians. | hepatitis b virus (hbv) infection is one of the major global health problems, especially in economically under-developed or developing countries. hbv infection can lead to a number of clinical outcomes including chronic infection, cirrhosis and liver cancer. it ranks among the top 10 causes of death, being responsible for around 1 million deaths every year. despite the availability of a highly efficient vaccine and potent antiviral agents, hbv infection still remains a significant clinical probl ... | 2012 | 25755457 |
| repeated exposure to trace amounts of woodchuck hepadnavirus induces molecularly evident infection and virus-specific t cell response in the absence of serological infection markers and hepatitis. | exposure to multiple small doses of hepatitis b virus (hbv) is a frequent occurrence in high-risk groups, including close relatives of infected individuals, primary care givers, and intravenous drug users. it remains uncertain whether such repeated contact may culminate in a symptomatic infection coinciding with hepatitis in individuals not immunoprotected. in this study, we evaluated consequences of multiple exposures to small, liver-nonpathogenic amounts of infectious hepadnavirus in the woodc ... | 2013 | 23135718 |
| perspectives for a vaccine against hepatitis delta virus. | hepatitis delta virus (hdv) causes severe hepatitis in carriers of hepatitis b virus (hbv). in ~90% of patients, hdv persists together with hbv and causes early development of cirrhosis and liver carcinoma. worldwide ~15 million people are coinfected with hbv-hdv. specific defects in the immune response causing persistence of the virus have not been identified. several approaches to develop a vaccine to prevent superinfection in the preclinical model of the woodchuck have failed. recent findings ... | 2012 | 22932974 |
| identification of an intrahepatic transcriptional signature associated with self-limiting infection in the woodchuck model of hepatitis b. | the woodchuck model of hepatitis b virus (hbv) infection displays many characteristics of human infection and has particular value for characterizing the host immune responses during the development of chronic infection. using the newly developed custom woodchuck microarray platform, we compared the intrahepatic transcriptional profiles of neonatal woodchucks with self-limiting woodchuck hepatitis virus (whv) infection to those woodchucks progressing to persistent whv infection. this revealed th ... | 2013 | 22806943 |
| molecular characterization of woodchuck interleukin-10 receptor and enhanced function of specific t cells from chronically infected woodchucks following its blockade. | interleukin 10 (il-10) is a pleiotropic cytokine acting on a variety of immune cells through the cell surface receptor (il-10r). it has been suggested to resuscitate antiviral immunity by interfering with il-10/il-10r pathway. the woodchuck model infected by woodchuck hepatitis virus (whv) represents an informative animal model to study hepatitis b virus (hbv) infection. in this study, the woodchuck il-10r (wil-10r) was molecularly cloned and characterized, showing high similarity of its nucleot ... | 2012 | 22784930 |
| hepatitis b virus x protein stimulates gene expression selectively from extrachromosomal dna templates. | chronic hepatitis b virus (hbv) infection is a major risk factor for liver cancer development. hbv encodes the hepatitis b virus x (hbx) protein that promotes transcription of the viral episomal dna genome by the host cell rna polymerase ii. here we provide evidence that hbx accomplishes this task by a conserved and unusual mechanism. thus, hbx strongly stimulates expression of transiently transfected reporter constructs, regardless of the enhancer and promoter sequences. this activity invariabl ... | 2012 | 22744635 |
| dna prime-adenovirus boost immunization induces a vigorous and multifunctional t-cell response against hepadnaviral proteins in the mouse and woodchuck model. | induction of hepatitis b virus (hbv)-specific cytotoxic t cells by therapeutic immunization may be a strategy to treat chronic hepatitis b. in the hbv animal model, woodchucks, the application of dna vaccine expressing woodchuck hepatitis virus (whv) core antigen (whcag) in combination with antivirals led to the prolonged control of viral replication. however, it became clear that the use of more potent vaccines is required to overcome whv persistence. therefore, we asked whether stronger and mo ... | 2012 | 22718818 |
| molecular characterization of the type i ifn receptor in two woodchuck species and detection of its expression in liver samples from woodchucks infected with woodchuck hepatitis virus (whv). | type i interferons (ifn-α/β) serve as the first line of defense against viral infection and share the same type i ifn receptor (ifnar) complex, which is composed of ifnar1 and -2. the eastern woodchuck (marmota monax) and chinese woodchuck (marmota himalayana) are suitable for studying hepatitis b virus (hbv) infection. here, the complete or partial sequences of the ifnars of both species were obtained and analyzed. small interference rnas targeting wifnar1 and -2 specifically down-regulated the ... | 2012 | 22705153 |
| role of toll-like receptor 2 in the immune response against hepadnaviral infection. | the toll-like receptor 2 (tlr2) has recently been recognized to play an important role in the pathogenesis of chronic hepatitis b virus (hbv) infection. in the present study, we examined the role of tlr2 in hepadnaviral infection in hepatoma cell lines and the woodchuck model. | 2012 | 22617154 |
| entecavir treatment of chronic hepatitis d. | hepatitis d virus (hdv) requires hepatitis b surface antigen (hbsag) to propagate infection and cause disease. entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis b virus (hbv) cccdna and woodchuck surface antigen. the aim of this study was to investigate the efficacy of entecavir in chronic hepatitis d (chd). | 2012 | 22573857 |
| subset of suz12/prc2 target genes is activated during hepatitis b virus replication and liver carcinogenesis associated with hbv x protein. | chronic hepatitis b virus (hbv) infection is a major risk factor for developing liver cancer, and the hbv x protein (px) has been implicated as a cofactor in hepatocyte transformation. we have shown that hbv replication as well as in vitro transformation by px are associated with induction of the mitotic polo-like kinase 1 (plk1) and down-regulation of the chromatin remodeling components suz12 and znf198. herein, we demonstrate the same inverse relationship between plk1 and suz12/znf198 in liver ... | 2012 | 22505317 |
| transcriptomic analysis of the woodchuck model of chronic hepatitis b. | the eastern woodchuck (marmota monax) is naturally infected with woodchuck hepatitis virus (whv), a hepadnavirus closely related to the human hepatitis b virus (hbv). the woodchuck is used as an animal model for studying chronic hepatitis b (chb) and hbv-associated hepatocellular carcinoma (hcc) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. to address this major limitation of the model, we report here the sequencing, assembly, and annotation ... | 2012 | 22431061 |
| hepatitis delta virus infects the cells of hepadnavirus-induced hepatocellular carcinoma in woodchucks. | hepatitis delta virus (hdv) is a natural subviral agent of human hepatitis b virus (hbv). hdv enhances liver damage during concomitant infection with hbv. the molecular pathogenesis of hdv infection remains poorly understood. to advance our understanding of the relationship between hdv infection and liver cancer, it was determined whether hdv could infect in vivo the cells of hepadnavirus-induced hepatocellular carcinoma (hcc). woodchucks (marmota monax) that were chronically infected with hbv-r ... | 2012 | 22334419 |
| modulation of regulatory t-cell activity in combination with interleukin-12 increases hepatic tolerogenicity in woodchucks with chronic hepatitis b. | regulatory t cells (treg) play a critical role in the modulation of immune responses to viral antigens in chronic viral hepatitis. woodchucks (marmota monax) infected with the woodchuck hepatitis virus (whv) represent the best animal model for chronic hepatitis b virus (hbv) infection. examination of intrahepatic and peripheral treg in uninfected and whv chronically infected woodchucks showed a significant increase of intrahepatic treg numbers in chronically infected animals, whereas no differen ... | 2012 | 22334260 |
| peromyscus as a model system for human hepatitis c: an opportunity to advance our understanding of a complex host parasite system. | worldwide, there are 185 million people infected with hepatitis c virus and approximately 350,000 people die each year from hepatitis c associated liver diseases. human hepatitis c research has been hampered by the lack of an appropriate in vivo model system. most of the in vivo research has been conducted on chimpanzees, which is complicated by ethical concerns, small sample sizes, high costs, and genetic heterogeneity. the house mouse system has led to greater understanding of a wide variety o ... | 2017 | 27498234 |
| a novel hepatovirus identified in wild woodchuck marmota himalayana. | hepatitis a virus (hav) is a hepatotropic picornavirus that causes acute liver disease worldwide. here, we report on the identification of a novel hepatovirus tentatively named marmota himalayana hepatovirus (mhhav) in wild woodchucks (marmota himalayana) in china. the genomic and molecular characterization of mhhav indicated that it is most closely related genetically to hav. mhhav has wide tissue distribution but shows tropism for the liver. the virus is morphologically and structurally simila ... | 2016 | 26924426 |
| immunogenicity evaluation of modified adenovirus vaccines expressing porcine circovirus type 2 capsid protein in pigs. | porcine circovirus type 2 (pcv2) adenovirus vaccine has been reported, but strong immune responses induced by adenovirus vector can decrease vaccine efficacy. to reduce the immunogenicity of adenovirus proteins, in previous study, we constructed the pcv2 adenovirus vaccine either modified with human cytomegalovirus first intron (intron a) and woodchuck hepatitis virus post-transcriptional regulatory element (wpre) to increase the expression of cap, or coexpressed porcine tumor necrosis factor-re ... | 2017 | 27996636 |
| modified recombinant adenoviruses increase porcine circovirus 2 capsid protein expression and induce enhanced immune responses in mice. | porcine circovirus type 2 (pcv2) is the primary viral pathogen of porcine circovirus associated disease (pcvad) and vaccination is an important method to prevent and control the disease. the expression of pcv2 capsid protein (cap) in adenovirus vector system has been investigated, but the poor immune responses limit its application. in this study, transcriptional enhancer element largest intron of the human cytomegalovirus (intron a) and woodchuck hepatitis virus post-transcriptional regulatory ... | 2017 | 27640437 |
| immune modulation by genetic modification of dendritic cells with lentiviral vectors. | our work over the past eight years has focused on the use of hiv-1 lentiviral vectors (lentivectors) for the genetic modification of dendritic cells (dcs) to control their functions in immune modulation. dcs are key professional antigen presenting cells which regulate the activity of most effector immune cells, including t, b and nk cells. their genetic modification provides the means for the development of targeted therapies towards cancer and autoimmune disease. we have been modulating with le ... | 2013 | 23726846 |
| codon optimization and woodchuck hepatitis virus posttranscriptional regulatory element enhance the immune responses of dna vaccines against infectious bursal disease virus in chickens. | the present study was undertaken to evaluate the protective efficacy of dna vaccines against infectious bursal disease virus (ibdv) in chickens and to determine whether codon optimization and the woodchuck hepatitis virus posttranscriptional regulatory element (wpre) could improve the immunogenicity of the dna vaccines. the vp2, vp243 and codon-optimized vp243 genes of ibdv were cloned into pcaggs vector, and designated as pcagvp2, pcagvp243 and pcagoptivp243, respectively. plasmids pcagwvp243 a ... | 2013 | 23631937 |
| powassan virus encephalitis resembling herpes simplex encephalitis. | a boy from new york traveling in nova scotia had olfactory hallucinations and other signs of temporal lobe involvement, leading to a diagnosis of herpes simplex encephalitis. the patient was treated with vidarabine and made a complete recovery. however, hemagglutination inhibition, complement fixation, and neutralization tests identified powassan virus (pow) as the pathogen. shortly before his trip to nova scotia, the patient had traveled in an area where pow encephalitis had occurred in humans ... | 1983 | 6297420 |
| rabies in rodents and lagomorphs in the united states, 1995-2010. | to assess the epidemiology of rabies in rodents and lagomorphs and provide information that will enable public health officials to make recommendations regarding postexposure prophylaxis for humans after contact with these animals. | 2014 | 25029313 |
| serial passage of a street rabies virus in mouse neuroblastoma cells resulted in attenuation: potential role of the additional n-glycosylation of a viral glycoprotein in the reduced pathogenicity of street rabies virus. | street rabies viruses are field isolates known to be highly neurotropic. however, the viral elements related to their pathogenicity have yet to be identified at the nucleotide or amino acid level. here, through 30 passages in mouse neuroblastoma na cells, we have established an attenuated variant of street rabies virus strain 1088, originating from a rabid woodchuck followed by 2 passages in the brains of suckling mice. the variant, 1088-n30, was well adapted to na cells and highly attenuated in ... | 2012 | 22248643 |
| protection of chickens against reticuloendotheliosis virus infection by dna vaccination. | the present study was undertaken to evaluate the ability of dna vaccination to protect chickens against reticuloendotheliosis virus (rev) infection and to determine whether codon optimization and the woodchuck hepatitis virus posttranscriptional regulatory element (wpre) could improve the immunogenicity of the dna vaccines. the wild-type and codon-optimized gp90 genes of rev were cloned into pcaggs vector, and designated as pcaggp90 and pcagoptigp90, respectively. plasmids pcagwgp90 and pcagwopt ... | 2013 | 23764274 |
| inclusion of the woodchuck hepatitis virus posttranscriptional regulatory element enhances aav2-driven transduction of mouse and human retina. | the woodchuck hepatitis virus posttranscriptional regulatory element (wpre) has been included in the transgene cassette of adeno-associated virus (aav) in several gene therapy clinical trials, including those for inherited retinal diseases. however, the extent to which wpre increases transgene expression in the retina is still unclear. to address this question, aav2 vectors containing a reporter gene with and without wpre were initially compared in vitro and subsequently in vivo by subretinal de ... | 2017 | 28325286 |
| molecular cloning, characterization and expression analysis of tim-3 and galectin-9 in the woodchuck model. | in recent years, a critical role for t cell immunoglobulin mucin domain 3 (tim-3) and its ligand galectin-9 (gal-9) has emerged in infectious disease, autoimmunity and cancer. manipulating this immune checkpoint may have immunotherapeutic potential and could represent an alternative approach for improving immune responses to viral infections and cancer. the woodchuck (marmot monax) infected by woodchuck hepatitis virus (whv) represents an informative animal model to study hbv infection and hcc. ... | 2017 | 28152393 |