| conserved transactivating and pro-apoptotic functions of hepadnaviral x protein in ortho- and avihepadnaviruses. | two established activities of the multifunctional human hepatitis b virus x-protein are its transactivating and pro-apoptotic potential. we analysed whether x-proteins from other orthohepadnaviruses and the newly discovered avihepadnaviral x-proteins have similar functions as hbx. previously, we have shown that hbx suppresses oncogenic transformation of primary rat embryo fibroblasts (ref) by induction of apoptosis. using this system, we found that the wildtype x-proteins of woodchuck, ground sq ... | 2002 | 12242658 |
| establishment of liver transplantation in woodchuck. | | 2002 | 12270413 |
| immunotherapy with a posttranscriptionally modified dna vaccine induces complete protection against metastatic neuroblastoma. | the successful induction of a t-cell-mediated tumor-protective immunity against poorly immunogenic malignancies remains a major challenge for cancer immunotherapy. we achieved this by immunization with a tyrosine hydroxylase (mth)-based dna vaccine, enhanced with the posttranscriptional regulatory acting rna element (wpre), derived from woodchuck hepatitis virus in combination with an antibody-cytokine fusion protein (ch14.18-il-2) that targets interleukin-2 (il-2) to the tumor microenvironment. ... | 2003 | 12393580 |
| comparison of cell culture systems for duck hepatitis b virus using sybr green quantitative pcr. | the hepadnaviridae family contains dna viruses such as human hepatitis b virus (hbv), woodchuck hepatitis b virus (whv), and duck hepatitis b virus (dhbv). dhbv is distributed in both wild and domestic ducks. hbv is a worldwide health problem with carriers at risk of developing cirrhosis and liver cancer. all medical staff and scientists working with hbv must be vaccinated, because of its highly contagious nature. dhbv is a safe surrogate for hbv because of their similarities. several cell cultu ... | 2002 | 12393148 |
| gene delivery to the eye using adeno-associated viral vectors. | adeno-associated virus (aav) vectors provide a useful way to deliver genes to the eye. they have a number of important properties which make them suitable for this purpose, not least their lack of significant pathogenicity and the potential for long-term transfection of retinal cells. the optimal methods for aav-mediated gene delivery are determined by the location and characteristics of the target cell type. efficient gene delivery to photoreceptors and pigment epithelial cells following subret ... | 2002 | 12413426 |
| measurements of vector-derived neurotrophic factor and green fluorescent protein levels in the brain. | demonstrating consistently reliable levels of expression is a critical part of any gene transfer study in order to assess variability and determine effective gene dosages. this article highlights some of the key methods for studying the expression levels of green fluorescent protein and neurotrophic factors after injections of adeno-associated virus (aav) vectors into the brain. the data demonstrate greater spread and higher levels of expression using the cytomegalovirus/chicken beta-actin (cba) ... | 2002 | 12413428 |
| viral pharmacodynamic model for (-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine (emtricitabine) in chronically infected woodchucks. | there is a need for adequate models of virus depletion in animals and humans as a function of drug dose in order to plan starting dose regimens in the clinic for new antiretroviral nucleoside agents. an indirect response pharmacodynamic model was fitted to link the plasma pharmacokinetics from a 28 day treatment with the nucleoside reverse transcription inhibitor emtricitabine [(-)-ftc], with the resulting virus depletion and recovery profiles in woodchucks chronically infected with woodchuck he ... | 2002 | 12448689 |
| cloning of interleukin-4 delta2 splice variant (il-4delta2) in chimpanzee and cynomolgus macaque: phylogenetic analysis of delta2 splice variant appearance, and implications for the study of il-4-driven immune processes. | the human interleukin-4 ( il-4) gene produces an exon 2-lacking alternative splice variant, termed il-4delta2, and described as a naturally occurring antagonist of il-4-driven activity. we report the isolation of an il-4delta2 cdna from chimpanzee ( pan troglodytes) bone marrow samples and cynomolgus macaque ( macaca fascicularis) activated peripheral lymph node cells. the complete il-4 cdna sequence from chimpanzee is also provided for the first time. the phylogenetic analysis of several known ... | 2002 | 12466896 |
| in vivo transmission and dynamics of deleted genomes after experimental infection of woodchuck hepatitis b virus in adult animals. | the presence of deleted genomes has been shown in a number of viral models including hepadnaviridae. the analysis of woodchuck hepatitis b virus (whv) population after experimental infection of woodchuck 197 (w197) with whv7-pi inoculum revealed the presence of two deleted genomes: dg600 lacking a 1330 bp region (core/polymerase/pres1) and dg900 showing a deletion of 869 nts (pol/pres/s). these mutants were also present in whv7-pi. the successive whv experimental infections in adult animals were ... | 2002 | 12416678 |
| expression of a new woodchuck ifn-alpha gene by a helper-dependent adenoviral vector in woodchuck hepatitis virus-infected primary hepatocytes. | recombinant interferon-alpha (rifn-alpha) is currently used in the treatment of viral hepatitis either alone or in combination with small molecules. however, this treatment is not very efficacious, and more effective protocols are needed. to this end, we have explored the woodchuck hepatitis system, validated as an infection model for vaccination and antiviral studies against human hepatitis b virus (hbv) infection. the lack of a woodchuck ifn-alpha (woifn-alpha) homolog has prevented study of v ... | 2002 | 12433282 |
| a pregenomic rna sequence adjacent to dr1 and complementary to epsilon influences hepatitis b virus replication efficiency. | hepatitis b virus (hbv) possesses a 3.2-kb partially double-stranded dna genome that is generated inside the nucleocapsid by the reverse transcription of the 3.5-kb pregenomic viral transcript. the initial steps in viral replication involve the recognition of an encapsidation signal termed epsilon (epsilon) at the 5'-end of the pregenomic rna by the hbv polymerase. the polymerase-bound pregenomic rna is subsequently incorporated into an immature nucleocapsid particle and minus-strand hbv dna syn ... | 2002 | 12482672 |
| mapping of the bovine immunodeficiency virus packaging signal and rre and incorporation into a minimal gene transfer vector. | gene transfer systems based on lentiviruses have emerged as promising gene delivery vehicles for human gene therapy due to their ability to efficiently transduce nondividing target cells. both primate and nonprimate lentiviruses have been used for construction of lentiviral vectors. an early generation of gene transfer system based on bovine immunodeficiency virus (biv) has been developed (r. d. berkowitz, h. ilves, w. y. lin, k. eckert, a. coward, s. tamaki, g. veres, and i. plavec, 2001, j. vi ... | 2002 | 12490399 |
| quantitative detection of hepadnavirus-infected lymphoid cells by in situ pcr combined with flow cytometry: implications for the study of occult virus persistence. | the detection of small amounts of viral pathogens in infected cells by classical pcr is hampered by a partial loss of virus nucleic acid due to extraction and by difficulties in discrimination between truly intracellular virus genome material and that possibly adhered to the cell surface. these impediments limit reliable identification of virus traces within infected cells, which are typically encountered in latent and persistent occult infections. in this study, hepadnavirus-specific in situ pc ... | 2003 | 12502813 |
| animal models for the study of hbv infection and the evaluation of new anti-hbv strategies. | our aim was to evaluate the anti-hbv activity of a novel l-nucleoside analog, 2',3'-dideoxy-2',3'-didehydro-beta-l-5-fluorocytidine (beta-l-fd4c), in study models of hbv infection. | 2002 | 12534778 |
| in vitro expression of human hepatitis b virus genomes carrying woodchuck hepatitis virus pre-s1 sequences. | many hepatitis b virus (hbv) in vivo experiments are unfeasible because this virus infects only humans. former studies demonstrated that the pre-s1 domain of the viral envelope protein l determines host range. therefore, we tried to generate hbv recombinants which might be able to infect woodchucks by exchanging different portions of the pre-s1 encoding gene with homologous parts from the related woodchuck hepatitis virus (whv) in a cloned hbv genome. in 6 mutants, 11-92 n-terminal hbv pre-s1 co ... | 2002 | 12566705 |
| immunogenic effects of woodchuck hepatitis virus surface antigen vaccine in combination with antiviral therapy: breaking of humoral and cellular immune tolerance in chronic woodchuck hepatitis virus infection. | a rational treatment strategy for chronic hepatitis b virus (hbv) infection might involve the modulation of immunity after the reduction of viremia and antigenemia. this strategy was tested in woodchucks chronically infected with the woodchuck hepatitis virus (whv) by combining antiviral treatment with 1-(2-fluoro-5-methyl-beta-l-arabinofuranosyl)-uracil (l-fmau) and therapeutic vaccination with whv surface antigen (whsag). | 2002 | 12566706 |
| stable genetic modification of human embryonic stem cells by lentiviral vectors. | human embryonic stem (hes) cells are pluripotent cells derived from the inner cell mass of the early preimplantation embryo. an efficient strategy for stable genetic modification of hes cells may be highly valuable for manipulating the cells in vitro and may promote the study of hes cell biology, human embryogenesis, and the development of cell-based therapies. here, we demonstrate that vectors derived from self-inactivating (sin) human immunodeficiency virus type 1 (hiv-1) are efficient tools f ... | 2003 | 12597917 |
| role of type 1 versus type 2 immune responses in liver during the onset of chronic woodchuck hepatitis virus infection. | immune response messenger rnas (mrna) were compared in liver during self-limited (resolved) and chronic neonatal woodchuck hepatitis virus (whv) infection. at week 14 postinfection (mid-acute phase), mrnas for leukocyte markers (cd3, cd4, cd8), type 1 cytokines and related transcription factors (ifn-gamma, tnf-alpha, stat4, t-bet), and il-10 were increased in livers from resolving infections, but mrnas of other type 1 (il-2) and type 2 (il-4, stat6, and gata3 markers remained at baseline levels. ... | 2003 | 12668969 |
| real-time quantitative reverse transcriptase-polymerase chain reaction as a method for determining lentiviral vector titers and measuring transgene expression. | the use of lentiviral vectors for basic research and potential future clinical applications requires methodologies that can accurately determine lentiviral titers and monitor viral transgene expression within target cells, beyond the context of reporter genes typically used for this purpose. here we describe a quantitative rt-pcr (qrt-pcr) method that achieves both goals using primer sequences that are specific for the woodchuck hepatitis virus posttranscriptional regulatory element (wpre), an e ... | 2003 | 12718761 |
| analysis of gene transfer and expression in skeletal muscle using enhanced eiav lentivirus vectors. | skeletal muscle is an attractive target tissue for gene therapy involving both muscle and nonmuscle disorders. hiv-1-based vectors transduce mature skeletal muscle; however, the use of these vectors for human gene therapy may be limited by biosafety concerns. in this study, we investigated gene transfer using lentivirus vectors based on the equine infectious anemia virus (eiav) in skeletal muscle in vitro and in vivo. eiav vectors transduce proliferating and differentiating c2c12 mouse muscle ce ... | 2003 | 12718906 |
| optimization of human erythropoietin secretion from mlv-infected human primary fibroblasts used for encapsulated cell therapy. | the transplantation of encapsulated cells genetically engineered to secrete human erythropoietin (hepo) represents an alternative to repeated injections of the recombinant hormone for the treatment of epo-responsive anemia. in the present study, the ability of primary human foreskin fibroblasts to secrete high levels of hepo and the importance of cis-acting elements and infection conditions on transgene expression level were assessed. | 2003 | 12666190 |
| molecular genetic and biochemical analysis of woodchuck (marmota monax) mhc class i polymorphism. | the woodchuck (marmota monax) is an animal model that is used in the study of human hepatitis b virus ( hbv ) infection. a knowledge of woodchuck mhc class i (mamo-i) genes and gene products is therefore essential for understanding the antigen-specific t-cell responses in this animal model. a number of mamo-i genes have been identified by molecular cloning and sequencing. however, the allelic nature of these genes has not been proven by classical genetics like the segregation analysis in familie ... | 2003 | 12694573 |
| scaffold attachment region located in a locus targeted by hepadnavirus integration in hepatocellular carcinomas. | the role of viral integration in hbv induced hepatocellular carcinoma (hcc) is still controversial. in the whv/woodchuck animal model, whv integration was found to activate the n-myc2 oncogene either by enhancer insertion in proximity of the gene, or by integration in a distantly located uncoding locus, win. in addition, we have reported that n-myc2 activation also results from whv integration in the b3n locus, located several kilobases downstream of n-myc2. in this work we report the search for ... | 2003 | 12787723 |
| woodchuck hepatitis virus post-transcriptional regulation element enhances transgene expression from adenovirus vectors. | in studies of both gene therapy and gene function, transgene expression can be modulated at both the transcriptional and post-transcriptional levels. in a previous study, we optimized the transcriptional regulatory elements for adenovirus (ad) vectors to mediate efficient transgene expression, including promoter, enhancer, intron, and poly(a) sequence. in the present study, we systematically investigated the ability of the woodchuck hepatitis virus post-transcriptional regulation element (wpre) ... | 2003 | 12787924 |
| universal primers for real-time amplification of dna from all known orthohepadnavirus species. | the family of hepadnaviridae is made up of members infecting birds (genus avihepadnavirus) or mammals (genus orthohepadnavirus). hepatitis b virus (hbv), the hepadnavirus infecting humans, can be divided into the seven genotypes a-g. by definition, genotypes differ by more than 8% at the nucleotide level. however, some genotypes differ by more than 14% from others. | 2003 | 12727526 |
| decreased oxidative dna damage and accelerated cell turnover in woodchuck hepatitis virus infected liver. | infection of newborn woodchucks with woodchuck hepatitis virus (whv) results in hepatocellular carcinoma (hcc). since oxidative damage may be carcinogenic, we investigated the relationship between whv infection and oxidative damage to hepatic lipids and dna. eastern woodchucks were infected with whv. hepatic lipid peroxidation was assessed in vitro in isolated hepatocytes by thiobarbituric acid reactive substances (tbars). oxidative dna damage was assessed in vivo in snap-frozen livers by 8-hydr ... | 2003 | 12697246 |
| evaluation of mitochondrial dna content and enzyme levels in tenofovir df-treated rats, rhesus monkeys and woodchucks. | the antiviral compound tenofovir df (gilead sciences) was evaluated for possible mitochondrial toxicity in rats, rhesus monkeys and woodchucks. animals were treated by oral gavage with tenofovir df, and the levels of mitochondrial enzymes cytochrome c oxidase and citrate synthase were assayed. in rats (6/group) treated daily for 28 days with 300 mg/kg tenofovir df the enzyme levels were unchanged versus control in liver, kidney, and skeletal muscle. in a parallel study, rats (6/group) were treat ... | 2003 | 12767469 |
| comparison of gene expression after intraperitoneal delivery of aav2 or aav5 in utero. | correction of diseases may be achieved by delivery of genes to stem cells and developing organ systems. our previous studies demonstrated life-long expression after in utero injection of adeno-associated virus (aav) serotype 2 in mice. in the present studies, we compared levels of expression using the elongation factor 1alpha (ef1alpha) or the cmv promoter in aav2 and aav5 linked to luciferase via intraperitoneal injection in day 15 fetuses in utero. an additional aav construct also contained th ... | 2003 | 12842432 |
| activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the hbx protein involved in hepatitis b virus replication. | human hepatitis b virus (hbv) hbx protein is a multifunctional protein that activates cellular signaling pathways and is thought to be essential for viral infection. woodchuck hbv mutants that lack hbx are unable to replicate in vivo or are severely impaired. hbv replication in hepg2 cells, a human hepatoblastoma cell line, is stimulated 5- to 10-fold by hbx protein. we have utilized the hepg2, hbx-dependent hbv replication system to study the effects of activators and inhibitors of cytosolic ca ... | 2003 | 12829810 |
| long-term transgene expression can be mediated in the brain by adenoviral vectors when powerful neuron-specific promoters are used. | adenoviral (ad) vectors are one of the most widely used tools for modelling gene therapy strategies. however, they have not been used in long-term models of neurological disease, as the period of time for which they mediate strong transgene expression is limited and/or variable. in this study we investigated the longevity of transgene expression in the brain when the powerful neuron-specific ad-synapsin (sy)-egfp-woodchuck hepatitis virus post-transcriptional regulatory element (wpre) vector cas ... | 2003 | 12825194 |
| highly efficient lentiviral gene transfer in cd34+ and cd34+/38-/lin- cells from mobilized peripheral blood after cytokine prestimulation. | because mobilized peripheral blood (mpb) represents an attractive source of cells for gene therapy, we investigated lentiviral gene transfer in cd34(+) cells and the stem/progenitor-cell-enriched cd34(+)/38(-)/lin(-) cell subset isolated from mpb. in this study, we used an optimized third-generation self-inactivating lentiviral vector containing both the central polypurine tract and the woodchuck hepatitis posttranscriptional regulatory element sequences and encoding enhanced green fluorescent p ... | 2003 | 12832700 |
| serologic evidence for a novel ehrlichia species in woodchucks (marmota monax) from pennsylvania, usa. | | 2003 | 12860605 |
| nitric oxide-dependent vasodilation maintains blood flow in true hibernating myocardium. | patients with chronic coronary artery disease may exhibit chronically depressed regional myocardial function, which can be reversed by revascularization. this was called hibernating myocardium, since it was thought that myocardial blood flow was also chronically reduced and since animals during true hibernation are thought to have downregulated function and blood flow. the missing link in this syllogism, whose discovery became our goal, was to measure myocardial blood flow during true hibernatio ... | 2003 | 12878480 |
| ultrasonography in the study of hepatocellular carcinoma in woodchucks chronically infected with whv. | the woodchuck hepatitis virus (whv)/woodchuck system is studied as animal model of human hepatocellular carcinoma (hcc) induced by chronic hepatitis b virus infection. the aim of the present study was the evaluation of ultrasound (us) liver examination in woodchuck as a routine method to detect hcc nodules and to follow their growth. sixteen woodchucks were included in the study. us liver examination was carried out in all animals using a 5 mhz convex scanner. macroscopic and microscopic examina ... | 2003 | 12869286 |
| a novel combination of promoter and enhancers increases transgene expression in vascular smooth muscle cells in vitro and coronary arteries in vivo after adenovirus-mediated gene transfer. | recombinant adenoviruses are employed widely for vascular gene transfer. vascular smooth muscle cells (smcs) are a relatively poor target for transgene expression after adenovirus-mediated gene delivery, however, even when expression is regulated by powerful, constitutive viral promoters. the major immediate-early murine cytomegalovirus enhancer/promoter (miemcmv) elicits substantially greater transgene expression than the human cytomegalovirus promoter (miehcmv) in all cell types in which they ... | 2003 | 12907954 |
| induction of antibodies to the pres region of surface antigens of woodchuck hepatitis virus (whv) in chronic carrier woodchucks by immunizations with whv surface antigens. | one goal of therapeutic vaccinations against chronic hepatitis b virus infection is to stimulate the b-cell responses to viral surface antigens in chronic carriers. here we investigated the induction of antibody responses to hepadnaviral surface antigens in the woodchuck model, with emphasis on the vaccination of woodchucks chronically infected with woodchuck hepatitis virus (whv). | 2003 | 12927927 |
| a hepadnavirus regulatory element enhances expression of a type 2 bovine viral diarrhea virus e2 protein from a bovine herpesvirus 1 vector. | recently, the possibility of using virus vectors to immunize cattle against selected bovine viral diarrhea virus (bvdv) genes has gained widespread interest. however, when we attempted to express the e2 protein from type 2 (890 strain) bvdv in a bovine herpesvirus 1 (bhv1) vector, we observed that expression was poor. this often happens when genes from a cytoplasmic virus are expressed in the cell nucleus. to counter this effect, we attempted to enhance expression by a strategy employed by virus ... | 2003 | 12885896 |
| retroviral vectors for high-level transgene expression in t lymphocytes. | efficient expression of genes transferred by retroviral vectors is a prerequisite for gene therapy, especially when the biological effect depends on the amount of transgene product. high-level gene expression is desirable for several gene therapy approaches involving t lymphocytes. we evaluated standard retroviral vectors with cis-regulatory control elements of the moloney murine leukemia virus (mo-mlv) with or without the human t cell-specific cd2 enhancer. for comparison, vectors containing th ... | 2003 | 12908967 |
| hbv x protein (hbx) interacts with general transcription factor tfiib both in vitro and in vivo. | in order to demonstrate the binding of hbv x protein (hbx) with the general transcription factor tfiib. | 1999 | 12903814 |
| hibernation and cortical electrical activity in the woodchuck (marmota monax). | | 1953 | 13056602 |
| physiologic studies of the groundhog (marmota monax). | | 1953 | 13094583 |
| spontaneous hepatomas in two woodchucks and a carcinoma of the testis in a badger. | | 1954 | 13201492 |
| [glycogen and lipid reserves in a marmot (arctomys marmota, marmota monax) in state of activity in summertime and during hibernation in winter]. | | 1957 | 13473275 |
| further experiences with hypothermia for intracardiac surgery in monkeys and groundhogs. | | 1953 | 13031466 |
| modulation of the outcome and severity of hepadnaviral hepatitis in woodchucks by antibodies to hepatic asialoglycoprotein receptor. | viral hepatitis is frequently accompanied by humoral autoimmune responses toward both organ-nonspecific and liver-specific antigens, but contribution of these reactivities to liver injury remains unrecognized. infection with woodchuck hepatitis virus (whv) has been identified as a potent inducer of autoantibodies against asialoglycoprotein receptor (anti-asgpr), a molecule essentially unique to hepatocytes that mediates clearance of desialylated serum proteins. in this study, we applied the whv- ... | 2003 | 12939589 |
| molecular characterization of cd28 and cytotoxic t-lymphocyte-associated antigen 4 (ctla-4) of woodchuck (marmota monax). | eastern woodchuck (marmota monax) became an important animal model to study the immunological processes in hepatitis b virus infection. to facilitate further study of t-cell responses in this model, we cloned and sequenced the cdnas of woodchuck cd28 and cytotoxic t-lymphocyte-associated antigen 4 (ctla-4), which play important roles for the regulation of t-cell activation by delivering the costimulation signals. according to the deduced amino-acid sequences, woodchuck cd28 showed a similarity o ... | 2003 | 12956876 |
| potassium deficiency in marmots during hibernation. | semiquantitation of potassium deficiency in the renal papillae indicates that woodchucks (marmota monax) are deficient in potassium annually during the time they subsist on stored fats. the deficiency begins prior to hibernation, progresses during hibernation, and, in males, continues during the immediate postemergence period. | 1961 | 13693392 |
| leptospira pomona infection in a woodchuck. preliminary report. | | 1960 | 13693848 |
| seasonal changes in the adrenal glands of woodchucks (marmota monax). | | 1962 | 13879283 |
| oxygen consumption, body temperature and heart rate of woodchucks entering hibernation. | | 1958 | 13559433 |
| impairment of muscle stretch reflexes in tick paralysis. | experiments with tick-paralyzed dogs and woodchucks have shown impairment of stretch reflexes in addition to partial paralysis at the neuromuscular junction. stretch reflexes disappear very early during paralysis, whereas nociceptive reflexes do not appear to be directly affected. the early incoordination and the ascending nature of the paralysis may be related to impairment of stretch reflex pathways. | 1960 | 13697384 |
| cerebrospinal nematodosis in pennsylvania groundhogs (marmota monax). | | 1964 | 14266874 |
| the influence of social interaction and season on weight change in woodchucks. | | 1965 | 14343914 |
| permeability studies on the red blood cell of the ground-hog, marmota monax. | | 1961 | 13698373 |
| effects of altered social structure on adrenal weights and morphology in populations of woodchucks (marmota monax). | | 1964 | 14181476 |
| powassan virus: summer infection cycle, 1964. | between may 1, and september 15, 1964, neutralizing antibody to powassan virus was detected in sera from 163 of 464 forest mammals captured in the powassan-north bay area of northern ontario. these included 159 of 358 groundhogs and four of 43 red squirrels. acquisition of antibody by juvenile groundhogs occurred principally during july and august. powassan virus strains were isolated from tick pools containing two to 15 ixodes cookei per pool which were removed from eight of 91 groundhogs in th ... | 1964 | 14230913 |
| gene therapy with brain-derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model. | to develop a modified adenoassociated viral (aav) vector capable of efficient transfection of retinal ganglion cells (rgcs) and to test the hypothesis that use of this vector to express brain-derived neurotrophic factor (bdnf) could be protective in experimental glaucoma. | 2003 | 14507880 |
| resistance of human hepatitis delta virus rnas to dicer activity. | the endonuclease dicer cleaves rnas that are 100% double stranded and certain rnas with extensive but <100% pairing to release approximately 21-nucleotide (nt) fragments. circular 1,679-nt genomic and antigenomic rnas of human hepatitis delta virus (hdv) can fold into a rod-like structure with 74% pairing. however, during hdv replication in hepatocytes of human, woodchuck, and mouse origin, no approximately 21-nt rnas were detected. likewise, in vitro, purified recombinant dicer gave <0.2% cleav ... | 2003 | 14581527 |
| increased in vitro and in vivo transgene expression levels mediated through cis-acting elements. | gene therapy for neurodegenerative diseases depends critically on the vector system to direct sustained and stable expression of the transgene. it is, however, a commonly observed phenomenon that transgene expression from currently available vectors is down-regulated following ex vivo gene transfer to the central nervous system (cns). in an attempt to circumvent this problem, we have systematically evaluated the potential of different cis-acting elements to increase and stabilize transgene expre ... | 2003 | 14661183 |
| hepatocyte turnover during resolution of a transient hepadnaviral infection. | we estimated the amount of hepatocyte turnover in the livers of three woodchucks undergoing clearance of a transient woodchuck hepatitis infection by determining the fate of integrated viral dna as a genetic marker of the infected cell population. integrated viral dna was found to persist in liver tissue from recovered animals at essentially undiminished levels of 1 viral genome per 1,000-3,000 liver cells, suggesting that the hepatocytes in the recovered liver were derived primarily from the in ... | 2003 | 14500915 |
| replacement of the murine leukemia virus (mlv) envelope gene with a truncated hiv envelope gene in mlv generates a virus with impaired replication capacity. | murine leukemia virus (mlv) capsid particles can be efficiently pseudotyped with a variant of the hiv-1 envelope protein (env) containing the surface glycoprotein gp120-su and a carboxyl-terminally truncated transmembrane (tm) protein, with only seven cytoplasmic amino acids. mlv/hiv pseudotyped vector particles acquire the natural host tropism of hiv-1 and their entry is dependent on the presence of cd4 and an appropriate co-receptor on the surface of the target cell. we describe here the const ... | 2003 | 14592772 |
| hepatic cirrhosis occurring in a young woodchuck (marmota monax) due to vertical transmission of woodchuck hepatitis virus (whv). | histologic and clinicopathologic findings of a woodchuck (marmota monax) vertically infected with woodchuck hepatitis virus (whv) are presented. the liver exhibits marked cirrhotic changes, which is characteristic of the pre-transformation phase of whv. at necropsy, the woodchuck exhibited ascites and the liver had a grossly nodular appearance. microscopically, focal hepatocyte necrosis and inflammatory cells were observed in midzonal and periportal areas in the liver. in macchiavellos stained s ... | 2003 | 14610377 |
| intravenous administration of an aav-2 vector for the expression of factor ix in mice and a dog model of hemophilia b. | previous experiments have demonstrated the stable expression of factor ix (fix) protein in mice and canine models of hemophilia b following portal vein gene transfer with a recombinant adeno-associated virus (raav) vector encoding fix. here, we present the results of studies that further optimized the raav vector transgene cassette used to express fix and explored the use of the less-invasive intravenous (i.v.) route of vector administration for the treatment of hemophilia b. first, a liver-spec ... | 2004 | 14712305 |
| immunization of woodchucks with adjuvanted shdag (p24): immune response and outcome following challenge. | the immunogenicity and the protection induced by an hepatitis delta virus (hdv) vaccine consisting of the small nucleoprotein (hdag) (p24) and adjuvanted with mf59 or freund's adjuvant (fa) were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (whv) and challenged with hepatitis delta virus. humoral and t-cell-mediated responses to hdag were measured. anti-hd antibodies appeared earlier in the fa/p24 animals. after challenge, all mf59/p24 vaccinated animals showed a re ... | 2004 | 14670328 |
| cis-acting sequences that contribute to the synthesis of relaxed-circular dna of human hepatitis b virus. | synthesis of the relaxed-circular (rc) genome of hepadnaviruses is a multistep process that requires template switching during reverse transcription. studies of duck hepatitis b virus indicated the presence of cis-acting sequences, distinct from the donor and acceptor sequences for the template switches, which contribute to the synthesis of rc dna. however, knowledge about cis-acting requirements distinct from the donor and acceptor sites for human hepatitis b virus (hbv) was lacking. in this st ... | 2004 | 14694095 |
| residual integrated viral dna after hepadnavirus clearance by nucleoside analog therapy. | we determined the frequency of integrated viral dna in the livers of three woodchucks chronically infected with the woodchuck hepatitis virus before and during 30 weeks of therapy with the nucleoside analog l-fmau [1-(2-fluoro-5-methyl-beta, l-arabinofuranosyl)uracil, clevudine]. we found that although viral covalently closed circular dna declined 20- to 100-fold, integrated viral dna showed no discernable decrease over the course of treatment. thus, chemotherapeutic clearance of covalently clos ... | 2004 | 14699050 |
| low doses of hepadnavirus induce infection of the lymphatic system that does not engage the liver. | woodchuck hepatitis virus (whv), which is closely related to human hepatitis b virus and is considered to be principally hepatotropic, invades the host's lymphatic system and persists in lymphoid cells independently of whether the infection is symptomatic and serologically evident or concealed. in this study, we show, with the woodchuck model of hepatitis b, that hepadnavirus can establish an infection that engages the lymphatic system, but not the liver, and persists in the absence of virus ser ... | 2004 | 14747538 |
| woodchuck hepatitis virus hepatocyte culture models. | | 2004 | 14762269 |
| the lancet fluke, a new parasite of the woodchuck. | | 1950 | 14792973 |
| effect of hibernation upon survival time following whole-body irradiation in the marmot (marmota monax). | | 1951 | 14845719 |
| kinetics of viremia and acute liver injury in relation to outcome of neonatal woodchuck hepatitis virus infection. | the kinetics of serum viral responses and acute liver injury were studied during neonatal woodchuck hepatitis virus (whv) infection in relation to the chronic or resolved outcome. the mean concentrations of serum whv dna and surface antigen were significantly higher by week 10 post infection in chronic infections compared to resolving infections, and diverged even further by the time of peak viral load development in serum (week 12). after week 12, these viral markers were detected less frequent ... | 2004 | 14748064 |
| measurement of cell-mediated immune response in woodchucks. | | 2004 | 14762256 |
| study of liver-specific expression of cytokines during woodchuck hepatitis virus infection. | | 2004 | 14762257 |
| adeno-associated viral glutamate decarboxylase expression in the lateral nucleus of the rat hypothalamus reduces feeding behavior. | in vivo gene transfer of glutamate decarboxylase (gad) has been explored as a means of inducing or increasing the production of the inhibitory amino-acid neurotransmitter, gaba. this strategy has been applied to neuroprotection, seizure prevention, and neuromodulation. in the present experiment, aav2 was used to transfer the genes for green fluorescence protein (gfp) and gad65 into the lateral nucleus of the rat hypothalamus. microinjection of 500 nl of aav2 resulted in transduction of a 0.25+/- ... | 2004 | 14961066 |
| insights into cardioprotection obtained from study of cellular ca2+ handling in myocardium of true hibernating mammals. | mammalian hibernators exhibit remarkable resistance to low body temperature, whereas non-hibernating (nhb) mammals develop ventricular dysfunction and arrhythmias. to investigate this adaptive change, we compared contractile and electrophysiological properties of left ventricular myocytes isolated from hibernating (hb) woodchucks (marmota monax) and control nhb woodchucks. the major findings of this study were the following: 1) the action potential duration in hb myocytes was significantly short ... | 2004 | 14962828 |
| b-cell-specific transgene expression using a self-inactivating retroviral vector with human cd19 promoter and viral post-transcriptional regulatory element. | retroviral gene transfer resulting in transgene expression selectively restricted to specific cell lineages would be desirable for many gene therapeutic applications. such transcriptional targeting of retroviruses can be accomplished by employing eukaryotic control elements in self-inactivating (sin) retroviral vectors, but use of these vectors is complicated by an accompanying reduction in viral titers. to overcome this restriction and address the influence of the post-transcriptional regulator ... | 2004 | 15029232 |
| identification of a glycosylation site in the woodchuck hepatitis virus pres2 protein and its role in protein trafficking. | the middle surface antigen (m-sag) of hepadnaviruses is one of three envelope proteins that share a common c-terminal s domain. m-sag contains the pres2 domain in addition to the s region. the pres2 region of woodchuck hepatitis virus (whv) contains a potential glycosylation site asn-gln-thr at amino acid (aa) positions 3-5. in this study, we mutated this site by site-directed mutagenesis and confirmed that glycosylation occurs here. in in vitro translation assays, the mutation thr to asn at aa ... | 2004 | 15039521 |
| synergistic interaction between aflatoxin b1 and hepatitis b virus in hepatocarcinogenesis. | chronic hepatitis b virus (hbv) infection and dietary exposure to aflatoxin b1 (afb1), two of the major risk factors in the multifactorial aetiology of hepatocellular carcinoma (hcc), co-exist in those countries with the highest incidences of and the youngest patients with this tumour, raising the possibility of a synergistic carcinogenic interaction between the two agents. experimental studies in hbv-transgenic mice and woodchucks infected with woodchuck hepatitis virus were the first to show a ... | 2003 | 14986813 |
| inhibition of cellular proteasome activities enhances hepadnavirus replication in an hbx-dependent manner. | the x protein (hbx) of the hepatitis b virus (hbv) is not essential for the hbv life cycle in vitro but is important for productive infection in vivo. our previous study suggests that interaction of hbx with the proteasome complex may underlie the pleiotropic functions of hbx. with the woodchuck model, we demonstrated that the x-deficient mutants of woodchuck hepatitis virus (whv) are not completely replication defective, possibly behaving like attenuated viruses. in the present study, we analyz ... | 2004 | 15078938 |
| optimal design of a single recombinant adeno-associated virus derived from serotypes 1 and 2 to achieve more tightly regulated transgene expression from nonhuman primate muscle. | recombinant adeno-associated virus (raav) vector supports long-term transgene expression from skeletal muscle in most mammals, including human. in some instances, the requirement for tight control of the transgene expression is expected. the original tetracycline-dependent system using the rtta (dox-on) transactivator displayed a baseline activity in the off state but improved versions are now available and need to be evaluated in a single-raav-vector strategy. in the present study we cloned, in ... | 2004 | 15006608 |
| integration of woodchuck hepatitis and n-myc rearrangement determine size and histologic grade of hepatic tumors. | integrations of woodchuck hepatitis virus (whv) dna and rearrangements of the n-myc 2 gene have been detected frequently in hepatocellular carcinoma (hcc) of eastern woodchucks (marmota monax) chronically infected with whv. fifty-five hepatocellular neoplasms and matched nontumor hepatic tissue specimens obtained postmortem from 13 chronic whv carriers were analyzed and the frequency of whv dna integrations and of n-myc rearrangements compared in tumors of different size and histologic grade. fo ... | 2004 | 15057905 |
| identification and molecular cloning of functional chicken il-12. | by a combination of large-scale sequencing, bioinformatics, and traditional molecular biology, we identified the long-searched-for cdna sequences encoding the homologues of the chicken il-12p35 and il-12p40 chains. these molecules are the first discovered nonmammalian il-12 subunits. the homologies of the chicken il-12p35 and il-12p40 proteins to the corresponding known subunits of various species, i.e., humans, sheep, horse, cat, bovine, mouse, and woodchuck, ranged between 21 and 42%, respecti ... | 2004 | 15034052 |
| adoptive transfer of immunity: a new strategy to interfere with severe hepatitis virus reinfection after woodchuck liver transplantation. | the effective transfer of humoral immunity to hepatitis b virus was first demonstrated after clinical and experimental bone marrow transplantation. this strategy is now evaluated in the woodchuck transplantation model, in which protection from reinfection can be tested. | 2004 | 15087755 |
| a novel class of phosphonate nucleosides. 9-[(1-phosphonomethoxycyclopropyl)methyl]guanine as a potent and selective anti-hbv agent. | 9-[1-(phosphonomethoxycyclopropyl)methyl]guanine (pmcg, 1), representative of a novel class of phosphonate nucleosides, blocks hbv replication with excellent potency (ec(50) = 0.5 microm) in a primary culture of hepg2 2.2.15 cells. it exhibits no significant cytotoxicity in several human cell lines up to 1.0 mm. it does not inhibit replication of human immunodeficiency virus (hiv-1) or herpes simplex virus (hsv-1) at 30 microm. many purine base analogues of 1 also exhibit inhibitory activity aga ... | 2004 | 15139764 |
| structure of pre-s2 n- and o-linked glycans in surface proteins from different genotypes of hepatitis b virus. | the middle-sized (m) surface proteins of hepatitis b virus (hbv) and other orthohepadnaviruses contain a conserved n-glycan in their pre-s2 domain, which is essential for the secretion of viral particles. recently, we also found o-glycans in the pre-s2 domain of m protein from woodchuck hepatitis virus (whv) and hbv genotype d. since the o-glycosylation motif is not conserved in all genotypes of hbv, the glycosylation patterns of hbv genotypes a and c were analysed. pre-s2 (glyco)peptides were r ... | 2004 | 15218190 |
| development of transgenic chickens expressing enhanced green fluorescent protein. | in this work we demonstrated the successful production of transgenic chickens expressing the enhanced green fluorescence protein (egfp) gene. replication-defective recombinant retroviruses produced from vesicular stomatitis virus g glycoprotein pseudotyped retrovirus vector system were injected beneath the blastoderm of non-incubated chicken embryos (stage x). from 129 injected eggs, 13 chicks hatched after 21 days of incubation. all hatched chicks were found to express vector-encoded egfp gene, ... | 2004 | 15219848 |
| alternative strategy for stress tolerance: opioids. | endogenous opioids have been implicated in the pathway of tolerance to stresses. hibernating tissues tolerate stress. serum from hibernating woodchucks (hibernation induction trigger [hit]), from summer nonhibernating animals (summer woodchuck active plasma [swap], and potential "hibernation opioid mimics" (d-ala(2) d leu(5) enkephalin [dadle]), and deltorphin d (delt d) were used as ischemic preconditioning agents (ipc) in an in vivo surgically induced cardiac ischemia rat model. comparison of ... | 2004 | 15123752 |
| suppression of lamivudine-resistant b-domain mutants by adefovir dipivoxil in the woodchuck hepatitis virus model. | adult woodchucks (marmota monax) chronically infected with woodchuck hepatitis virus (whv) were treated orally with lamivudine (15 mg/kg per day) for 57 weeks. after 20 weeks of treatment a 2-3 log reduction in serum whv dna was detected. serum titers of whv then increased gradually, in the presence of lamivudine treatment, reaching pre-treatment values by week 40. viral recrudescence was associated with development of mutations in the b domain of the whv polymerase gene. mutations observed in t ... | 2004 | 15302140 |
| the hybrid cytomegalovirus enhancer/chicken beta-actin promoter along with woodchuck hepatitis virus posttranscriptional regulatory element enhances the protective efficacy of dna vaccines. | dna vaccines represent a novel and powerful alternative to conventional vaccine approaches. they are extremely stable and can be produced en masse at low cost; more importantly, dna vaccines against emerging pathogens or bioterrorism threats can be quickly constructed based solely upon the pathogen's genetic code. the main drawback of dna vaccines is that they often induce lower immune responses than traditional vaccines, particularly in nonrodent species. thus, improving the efficacy of dna vac ... | 2004 | 15210816 |
| effect of a combination of clevudine and emtricitabine with adenovirus-mediated delivery of gamma interferon in the woodchuck model of hepatitis b virus infection. | our aim was to evaluate the antiviral effect of a combination of two nucleoside reverse transcriptase inhibitors, emtricitabine (ftc) and clevudine (l-fmau), with the addition of an adenovirus-driven delivery of recombinant gamma interferon (ifn-gamma) in the woodchuck model of hepatitis b virus infection. six woodchuck hepatitis virus (whv)-infected woodchucks received l-fmau (10 mg/kg) plus ftc (30 mg/kg) intraperitoneally for 8 weeks; six other animals received in addition an intravenous inje ... | 2004 | 15215126 |
| hepatocellular carcinoma in black-tailed prairie dogs (cynomys ludivicianus): tumor morphology and immunohistochemistry for hepadnavirus core and surface antigens. | from 1994 to 2002, tissues from 61 prairie dogs were submitted to northwest zoopath for histopathology. of these, 12 (20%) had hepatocellular carcinoma (hcc). three were pets submitted from private veterinary practices. the others were submitted from zoos in the united states. all were adults, ranging from young adult to 7 years of age, with average age of 5.1 years. the most common clinical signs were weight loss, lethargy, palpable abdominal mass, and respiratory difficulty. all tumors were we ... | 2004 | 15232135 |
| adenovirus-based gene therapy during clevudine treatment of woodchucks chronically infected with woodchuck hepatitis virus. | interferon-alpha (ifn-alpha) is a potent suppressor of hepatitis b virus (hbv) replication in the hbv-transgenic mouse, depleting virus replication intermediates from infected hepatocytes via pathways mediated by interferon-gamma (ifn-gamma) and tumor necrosis factor alpha (tnf-alpha). it has also been hypothesized that cytokines induce curing of infected hepatocytes via non-cytolytic pathways during resolution of transient hepadnavirus infections. we have therefore evaluated therapy of chronic ... | 2004 | 15327895 |
| a dose-finding study of once-daily oral telbivudine in hbeag-positive patients with chronic hepatitis b virus infection. | current therapy for chronic hepatitis b is suboptimal as a result of limited durable response rates, cumulative viral resistance, and/or poor tolerability. telbivudine has potent antiviral activity against hepatitis b virus (hbv) in vitro and in the woodchuck model and has a promising preclinical safety profile. in this first clinical study of telbivudine, safety, antiviral activity, and pharmacokinetics were assessed in 43 adults with hepatitis b e antigen-positive chronic hepatitis b. this pla ... | 2004 | 15349912 |
| lead accumulation in woodchucks (marmota monax) at small arms and skeet ranges. | increasing concern regarding the stewardship of us army lands requires a proactive program to evaluate sites of potential risk. small arms and upland skeet ranges are a potentially significant source of lead exposure for burrowing mammals. woodchucks (marmota monax) were evaluated for lead exposure in a previously used upland skeet range and a small arms range, respective to animals collected at two nearby reference locations. soil lead concentrations collected at burrow entrances on the firing ... | 2004 | 15327881 |
| cross-species hybridization: characterization of gene expression in woodchuck liver using human membrane arrays. | total rna from normal adult woodchucks was analyzed using membrane arrays containing human cdna clones, and the gene expression patterns were compared to human liver. various hybridization and wash conditions were examined. in both the woodchuck and human livers, 352 genes were identified as highly expressed (z-scores > or =1.96). these genes represented numerous liver functions: transcription, rna processing, signal transduction, protein synthesis and degradation, as well as enzymes. several ge ... | 2004 | 15332280 |
| helper-dependent adenoviral vector-mediated delivery of woodchuck-specific genes for alpha interferon (ifn-alpha) and ifn-gamma: ifn-alpha but not ifn-gamma reduces woodchuck hepatitis virus replication in chronic infection in vivo. | alpha interferon (ifn-alpha) and ifn-gamma are able to suppress hepadnavirus replication. the intrahepatic expression of high levels of ifn may enhance the antiviral activity. we investigated the effects of woodchuck-specific ifn-alpha (wifn-alpha) and ifn-gamma(wifn-gamma) on woodchuck hepatitis virus (whv) replication in vivo by helper-dependent adenoviral (hd-ad) vector-mediated gene transfer. the expression of biologically active ifns was demonstrated in vitro after transduction of woodchuck ... | 2004 | 15331744 |
| interferon-gamma-associated responses to woodchuck hepatitis virus infection in neonatal woodchucks and virus-infected hepatocytes. | acute hepatitis and recovery from woodchuck hepatitis virus (whv) infection involves increased intrahepatic expression of interferon-gamma (ifn-gamma) and tumour necrosis factor-alpha (tnf-alpha) mrnas. in the present study, recovery correlated with increased intrahepatic expression of mrnas for major histocompatibility complex class 1 (mhc1), beta(2)-microglobulin, 2'5'-oligoadenylate synthetase (2'5'-oas), and indoleamine dioxygenase (ido). by comparison, acute whv infection progressing to chr ... | 2004 | 15357645 |
| persistence of isolated antibodies to woodchuck hepatitis virus core antigen is indicative of occult infection. | antibodies against virus nucleocapsid (anticore) normally accompany hepadnaviral hepatitis but they may also occur in the absence of symptoms and other serological indicators of the infection. this situation can be encountered following a clinically and serologically unapparent exposure to hepatitis b virus (hbv) or after recovery from hepatitis b. in this study, woodchucks inoculated with woodchuck hepatitis virus (whv) were investigated to determine the relationship between anticore detection ... | 2004 | 15382154 |
| self-inactivating retroviral vectors with improved rna processing. | three rna features have been identified that elevate retroviral transgene expression: an intron in the 5' untranslated region (5'utr), the absence of aberrant translational start codons and the presence of the post-transcriptional regulatory element (pre) of the woodchuck hepatitis virus in the 3'utr. to include such elements into self-inactivating (sin) vectors with potentially improved safety, we excised the strong retroviral promoter from the u3 region of the 3' long terminal repeat (ltr) and ... | 2004 | 15372067 |
| hepatocellular carcinoma in the woodchuck model of hepatitis b virus infection. | the eastern woodchuck ( marmota monax ) harbors a dna virus (woodchuck hepatitis virus [whv]) that is similar in structure and replicative life cycle to the human hepatitis b virus (hbv). like hbv, whv infects the liver and can cause acute and chronic hepatitis. furthermore, chronic whv infection in woodchucks usually leads to development of hepatocellular carcinoma (hcc) within the first 2-4 years of life. the woodchuck model has been important in the preclinical evaluation of safety and effica ... | 2004 | 15508096 |