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At least 307 records · Page 17Linked to original sources
PubMed1998

[Antisense oligodeoxynucleotide targeted at the pre-s region of DHBV could inhibit virus replication in vivo].

To study the antiviral effect of antisense oligodeoxynucleotide (AS-ODN), AS-ODN phosphotioates targeted to DHBV Pre-S region (951-968nt) (5'-TATCTCCTCCATTGTTTG-3') was synthesized. Two day-old ducklings were infected i.p. with 150 microliters of DHBV (3 x 10(8) copies/ml DHBV). After 12 days, 6 DHBsAg and DHBV DNA positive ducks were divided into two groups. In treated group, each duck was injected i.v. AS-ODN 20 micrograms/gram weight/day for 10 dyas successively, while in the control group, each duck received the same volume of normal saline for 10 days. Sera from ducks prior to treatment and treated after 6, 10 days were collected, and after 10 days ducks were sacrificed and livers were examined. DHBsAg was significantly decreased in all three treated ducks after 10 days of AS-ODN treatment. One of these ducks showed decreased DHBsAg even 6 days after treatment. Two out of three treated ducks showed decreased serum DHBV DNA, while one remained unchanged. In contrast, none of the control group showed decreased DHBsAg and DHBV DNA did not change. By Southern blot, DHBV DNA in the liver significantly decreased in 2/3 of the treated ducks and decreased in the other duck. In all control ducks, DHBV DNA remained strongly positive. Data indicated that AS-ODN targeting at Pre-S region could partly inhibit the replication of DHBV.

Animals↗
PubMed1998

[The effect of ribozyme RzDS on duck hepatitis B virus].

To study the effect of ribozyme in vivo, the hammerhead ribozyme RzDS was designed and synthesized, which aims at the pregenome RNA of DHBV(LJ-76) at the 736 site of the genome. The RzDS cleaved efficiently its substrate in vitro. We constructed pJ-RzDS, in which RzDS was inserted into pJ120 plasmid under the control of PII promoter. After homogenous recombination with the vaccinia virus, Tian Tan strain, we got the recombinant(V-RzDS) which carried RzDS. V-RzDS was injected into nestling Beijing ducks preinfected with DHBV. On the tenth day after intravenous injection, DHBV DNA and DHBsAg in serum were detected. The quantity of DHBV DNA and DHBsAg were evidently lower than that of the controls, when V-RzDS injection was simultaneously given with DHBV. It suggests that RzDS can block replication and expression of DHBV in vivo.

Animals↗
PubMed2001

[Anti-virus effect of combination of attenuated measles virus with 3TC on duck hepatitis B model].

OBJECTIVE: To evaluate the anti-virus effect of combination of attenuated measles virus with 3TC on duck hepatitis B model. METHODS: Guanzhou brown spot ducklings infected with DHBV were divided into three groups. Drug treatments including measles vaccine, 3TC and both measles vaccine and 3TC were given in the 13th day after the infection, respectively. Serum samples were obtained from all ducklings before, during and after treatment at different times and stored at -70 degrees C. DHBV DNA was detected by Dot-blot hybridization. RESULTS: Compared with the levels of DHBV DNA before and after treatment, no statistic difference was found in group of 3TC alone. The levels of DHBV DNA were not changed in group of measles vaccine alone in early stage, but decrease of DHBV DNA occurred after stopping treatment (comparison of the levels T13 with before treatment and T13 of positive group, P < 0.01 and P < 0.05, respectively). DHBV DNA level in group of measles vaccine combined with 3TC was obviously lower at 5th day after the treatment than in both measles vaccine and 3TC alone groups at the same time(P < 0.05 and P < 0.01, respectively), and it remained low when the treatment was discontinued. CONCLUSION: Attenuated measles virus combined with 3TC may have early and long-lasting inhibiting effect on the replication of DHBV.

Animals↗
PubMed2000

[Inhibition of extracts of ampelopsis sinica roots on DHBVsAg in sera of ducklings].

The ducklings, which are infected with Duck HBV to produce DHBVsAg in sera in advance, are treated with extracts from Ampelopsis sinica roots and some of them are treated with interferon alpha (INF) as positive control group. According the titer of DHBVsAg in Ducklings sera and the results of observing the tissues of the duckling's livers, it is demonstrated that the extracts of Ampelopsis sinica roots possess a certain action inhibiting DHBV and the action is enduring.

Ampelopsis↗
PubMed2003

[Inhibition of duck hepatitis B virus DNA replication by antisense phosphorothioate oligodeoxynucleotides in vitro and in vivo].

BACKGROUND: To determine the feasibility of inhibition of duck hepatitis B virus (DHBV) DNA replication by antisense phosphorothioate oligodeoxynucleotides corresponding to DHBV transcription region. METHODS: The authors designed three antisense phosphorothioate oligodeoxynucleotides which correspond to DHBV PreS1,PreS2 and S antigen gene promotors respectively. The DNA replication level was detected with Southern blot method and cpm calculation. RESULTS: Primary duck hepatocyte culture was treated with 1.5 micromol/L antisense oligodeoxynucleotides in vitro, all the antisense fragments caused a firm inhibition of viral DNA replication and the inhibition rates were 61.5%, 69.3% and 62.4%, respectively. In vivo, the animals were treated with 10 microgram/g PreS1 antigen gene promotor antisense oligodeoxynucleotides per day for 6 days and a very strong inhibition rate of 87.9% was obtained. CONCLUSIONS: The results demonstrated the potential clinical application of antisense phosphorothioate oligodeoxynucleotides in clinics.

Animals↗
PubMed1992

Direct immunofluorescence testing for immunoglobulin deposits in haired skin, nasal planum and footpads of woodchuck hepatitis virus-infected woodchucks with chronic hepatitis and multiple hepatocellular carcinomas.

The purpose of this study was to determine the frequency of immunoglobulin deposition in the haired skin, footpads, and nasal planums of 10 WHV-infected woodchucks with chronic hepatitis and hepatocellular carcinoma and compare these results with those reported in humans. Immunoglobulin deposition was detected in the skin samples of 3 of 10 woodchucks. Granular deposits were revealed in the superficial dermal blood vessels of the nasal planum, lateral thoracic skin, and footpads in 1 animal each. In 1 of these animals, (lateral thorax) immunoglobulin deposition was concurrently present at the basement membrane zone.

Animals↗
PubMed1992

Mammalian hepatitis B viruses and primary liver cancer.

Hepatitis B virus is a major etiologic agent in the development of human hepatocellular carcinoma, but the precise role of the virus in the tumorigenic process is still unclear. Recent studies of naturally occurring animal models, such as woodchucks and squirrels infected with hepatitis B-like viruses (hepadnaviruses) have revealed different oncogenic strategies and outlined the predominant role of myc genes in rodent hepatomas. Higher oncogenicity of woodchuck hepatitis virus has been correlated with a direct contribution of the virus as an insertional mutagen of myc genes: c-myc, N-myc and predominantly the woodchuck N-myc retroposon. In contrast, rare viral integration events but frequent amplifications of c-myc characterize ground squirrel hepatitis virus-induced tumors, indicating that hepadnaviruses may contribute in malignant transformation through different, direct or indirect ways.

Animals↗
PubMed1992

Microscopic anatomy of the skin of the woodchuck (Marmota monax): comparison of woodchuck hepatitis virus-infected and non-infected animals.

Thirty-three woodchucks were used in this study. Seventeen animals were healthy adults, not infected with woodchuck hepatitis virus (WHV); 10 were healthy adults infected with WHV; 4 were noninfected neonates; 2 were infected neonates. Within the 4 groups of woodchucks, no histologic differences were detected on the basis of sex or age. Neither were histologic findings different between infected and noninfected woodchucks of similar ages. The average thickness of skin (as measured from the skin surface to the inner limit of the dermis) from the general haired body area was 2394 microns. The skin was thickest on dorsal body areas, and gradually became thinner on ventral body and medial limb areas. The epidermis consisted of 4 layers: stratum basale, stratum spinosum, stratum granulosum, and stratum corneum. A stratum lucidum was present only in the epidermis of the footpads. There was no clear distinction between the superficial dermis and the deep dermis, except for the subtle differences in arrangement and size of collagen fibers. Elastic fibers were seen throughout the dermis, being more prominent in the superficial portion. Both compound and simple hair follicle arrangements were seen, with compound being more common. The arrectores pilorum muscles were largest in the skin over the dorsal body areas. Sebaceous glands were present either within the outer root sheath of hair follicles or in the dense connective tissue surrounding hair follicles. No apocrine sweat glands were found. However, there were abundant eccrine sweat glands in the subcutaneous fat of the footpads.

Animals↗
PubMed1997

[Anti-virus effect of hepatocyte stimulating substance (HSS) on duck hepatitis B virus in vivo].

We used one day old Beijing ducklings infected by duck hepatitis B virus as experimental model to observe anti-virus effect of HSS. Beijing ducklings hatched within one day were injected intravenously with duck hepatitis B virus (DHBV). Positive DHBV-DNA in ducklings' sera were detected 7 days later. Serum samples were obtained from all ducklings before, during and after drug treatment at different times and stored at -70 degrees C. The collected samples were detected DHBV-DNA by dot-blot hybridization test at the same time. The therapeutic effects were evaluated by OD value of dot-blot and by the inhibitory rate of DHBV-DNA. The results showed that HSS (with 50 mg/kg/day and 200 mg/kg/day) were effective in inhibition of DHBV-DNA during and after drug treatment, especially in the HSS group of large dosage. The inhibitory effect appeared early and high dynamic. The inhibitory rate of DHBV-DNA during and after drug treatment were higher than the NS group (P < 0.05). No inhibitory effect was observed in NS group. The hepatic biopsy showed HSS groups had milder damage than NS group, indicating that the HSS could inhibit the replication of DHBV-DNA in Beijing ducklings.

Animals↗
PubMed1997

[Inhibitory effect of trisodium phosphonoformate (PFA) on duck hepatitis B virus (DHBV) DNA in vivo].

This paper described that DHBV infected ducklings were given with PFA 250 mg, 125 mg, 62.5 mg/kg b. i. d for 21 days intraperitioneally (i.p.) and dynamics of duck hepatitis B virus DNA (DHBV DNA) and duck hepatitis B surface antigen (DHBsAg) were detected in serum and distribution of DHBV DNA was tested in liver, kidney, pancreas and spleen. Supercoiled DNA (SC DNA) extracted from liver was analysed with Southern blot. The results showed that PFA in a dose of 125 mg and 250 mg/kg inhibited significantly the serum DHBsAg; doses of 125 mg and 250 mg/kg inhibited the serum DHBV DNA from 14 to 21 days, and dose of 250 mg/kg inhibited the serum DHBV DNA earlier even at 7 days after being given with PFA. Doses of 125 mg and 250 mg/kg inhibited obviously DHBV DNA in liver and kidney, but no inhibition was found in spleen and pancreas. The replication of DHBV DNA in liver of ducklings treated with PFA in a dose of 250 mg/kg for 21 days showed that the PFA inhibited significantly the synthesis of linear DNA (L DNA), relaxed circular DNA (RC DNA) and SC DNA. But DHBsAg and DHBV DNA in serum and DHBV DNA in liver, kidney, pancreas and spleen after treated with PFA for 21 days were still present, this meant that PFA treatment didn't clear off the virus genome in infected ducklings, the "rebounding" of DHBV appeared after cessation of the PFA treatment.

Animals↗
PubMed1992

The structure of hepadnaviral core antigens. Identification of free thiols and determination of the disulfide bonding pattern.

A set of wild-type and mutant human, woodchuck, and duck hepatitis viral core proteins have been prepared and used to study the free thiol groups and the disulfide bonding pattern present within the core particle. Human (HBcAg) and woodchuck (WHcAg) core proteins contain 4 cysteine residues, whereas duck (DHcAg) core protein contains a single cysteine residue. Each of the cysteines of HBcAg has been eliminated, either singly or in combinations, by a two-step mutagenesis procedure. All of the proteins were shown to have very similar physical and immunochemical properties. All assemble into essentially identical core particle structures. Therefore disulfide bonds are not essential for core particle formation. No intra-chain disulfide bonds occur. Cys107 is a free thiol buried within the particle structure, whereas Cys48 is present partly as a free sulfhydryl which is exposed at the surface of the particle. Cys61 is always and Cys48 is partly involved in interchain disulfide bonds with the identical residues of another monomer, whereas Cys183 is always involved in a disulfide bond with the Cys183 of a different monomer. WHcAg has the same pattern of bonding, whereas DHcAg lacks any disulfide bonds, and the single free sulfhydryl, Cys153 which is equivalent to Cys107 of HBcAg, is buried.

Amino Acid Sequence↗
PubMed1992

Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax).

Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six.

Animals↗
PubMed1992

Nitrite and nitrosamine synthesis by hepatocytes isolated from normal woodchucks (Marmota monax) and woodchucks chronically infected with woodchuck hepatitis virus.

Hepatocytes isolated from woodchucks (Marmota monax) were shown to produce nitrite in vitro from L-arginine after stimulation with lipopolysaccharide (LPS). Hepatocytes isolated from woodchucks that were chronic carriers of woodchuck hepatitis virus formed twice as much nitrite as hepatocytes from noninfected animals. Nitrite synthesis by hepatocytes was directly related to L-arginine and LPS concentrations in the tissue culture medium and reached a plateau at 0.5 mM L-arginine and 1.0 micrograms/ml LPS. LPS-stimulated hepatocytes nitrosated morpholine to form N-nitrosomorpholine in the presence of L-arginine at a physiological pH of 7.4. There was a 10-fold increase in N-nitrosomorpholine production when hepatocytes were stimulated with LPS compared to unstimulated hepatocytes under similar conditions when both nitrite and morpholine were directly added to the medium. NG-monomethyl-L-arginine, a selective inhibitor of nitric oxide synthase, inhibited formation of both nitrite and N-nitrosomorpholine. These results demonstrate that nitrosating agents are formed in hepatocytes via the L-arginine-nitric oxide pathway. This suggests that endogenous formation of carcinogenic N-nitroso compounds could influence the process of hepatocarcinogenesis in woodchucks with chronic woodchuck hepatitis virus infection.

Animals↗
PubMed1991

Hepatocellular carcinoma in Richardson's ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection.

During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species.

Animals↗
PubMed1990

Alpha-fetoprotein in the woodchuck model of hepadnavirus infection and disease: normal physiological patterns and responses to woodchuck hepatitis virus infection and hepatocellular carcinoma.

Persistent infection of the eastern woodchuck (Marmota monax) with the woodchuck hepatitis virus (WHV) produces disease sequelae similar to those observed in humans with persistent hepatitis B virus infection, including hepatocellular carcinoma (HCC). To further characterize serological markers of HCC in the woodchuck, serum alpha-fetoprotein (AFP) was measured under normal physiological conditions and following infection with WHV. Serum AFP was elevated in association with WHV-induced hepatitis and HCC and was a useful indicator of hepatic responses in individual animals throughout the course of experimental WHV infection. The frequent occurrence of normal elevations in serum AFP during the fall and winter, however, limits the use of AFP as a marker for early detection of HCC. The present temporal studies of AFP responses in WHV-infected woodchucks have identified several stages of infection where virological and cellular interactions can be investigated at the molecular level. Studies of AFP in the woodchuck model should provide opportunities to further elucidate the physiological and immunological functions of AFP and to understand virus-host cell interactions during the course of experimental hepadnavirus infection leading to HCC.

Aging↗
PubMed1991

Cyclosporin A modulates the course of woodchuck hepatitis virus infection and induces chronicity.

Immunosuppression is known to influence the state of chronic hepatitis B virus infection, and is thought to increase the risk of developing chronic infection in newly exposed individuals. Cyclosporin A (CsA), an immunosuppressive agent that inhibits Th cell function, was administered to woodchucks chronically infected with woodchuck hepatitis virus (WHV), and resulted in a decreased severity of chronic hepatitis and an increased viremia during the treatment. Adult woodchucks inoculated with WHV and given CsA for 14 wk had increased viremias, decreased acute phase liver injury, and developed chronic infections at a higher rate compared with immunocompetent woodchucks given virus alone (chronicity in seven of seven WHV + CsA + vs zero of nine WHV + CsA-; p less than 0.001). These results in a relevant animal model of hepatitis B virus infection indicate: 1) that liver injury in acute hepadnavirus infections is immune-mediated and not a direct cytopathic effect of virus replication; 2) that Th cells function in the inflammatory response and in the immunologic control of hepadnavirus infection; and 3) that suppression of Th cell function in acute hepadnavirus infection decreases liver injury but alters the outcome of infection in favor of chronicity. These results also suggest continued challenges in the application of CsA in liver transplantation for hepatitis B virus-induced diseases.

Acute Disease↗
PubMed1991

Elevated formation of nitrate and N-nitrosodimethylamine in woodchucks (Marmota monax) associated with chronic woodchuck hepatitis virus infection.

Nitrate balance and N-nitrosodimethylamine (NDMA) excretion were studied in woodchucks chronically infected with woodchuck hepatitis virus (WHV). Twenty-four-h urinary recovery of a bolus dose of [15N]nitrate was 54 +/- 12% in woodchucks. WHV-infected animals formed 3-fold more nitrate endogenously than did control animals (P less than 0.01). Treatment of WHV-infected animals with Escherichia coli lipopolysaccharide increased nitrate excretion 15-fold, while uninfected animals increased nitrate excretion 4-fold. The endogenous formation of NDMA was higher in WHV-infected woodchucks than in uninfected controls. After administration of L-[15N2]arginine, [15N]nitrate, and [15N]NDMA were detected in urine indicating that arginine is a precursor of biosynthesized nitrate and the hepatocarcinogen NDMA. NDMA probably results from the formation of nitrosating agents during the oxidation of arginine to oxides of nitrogen and citrulline. Woodchucks chronically infected with WHV develop hepatocellular carcinomas with high frequency. Our observations suggest an additional mechanism that may be involved in the pathogenesis of hepatocellular carcinoma associated with chronic WHV infection.

Animals↗