Longitudinal analysis of hepatitis C virus infection and genetic drift of the hypervariable region.

Hepatitis C virus (HCV) infections in a cohort of chimpanzees were studied retrospectively. All animals had been inoculated intravenously with materials derived from a single-source chimpanzee plasma implicated in non-A, non-B hepatitis, prepared by extensive ultracentrifugation. Anti-HCV and HCV RNA were monitored by the confirmatory line immunoassay and by an RNA-capture polymerase chain reaction method, respectively.

Oral famciclovir against duck hepatitis B virus replication in hepatic and nonhepatic tissues of ducklings infected in ovo.

Detection of hepadnaviral DNA in extrahepatic tissues of human and animal models of hepatitis B virus (HBV) has raised the question of whether virus replication in organs other than the liver could be targeted for the treatment of chronic hepatitis B. Since duck hepatitis B virus (DHBV) replication is dynamic in the liver, kidney, pancreas, and spleen of newly hatched ducklings infected in ovo, we used the duck model and the new antiherpesvirus agent, famciclovir (FCV), to determine whether antiviral effect of nucleoside analogues on DHBV replication is pluripotential. Day-old ducklings hatched from eggs laid by a DHBV-carrier duck were bled and administered FCV (25 mg/kg/bd) orally for periods of 1, 2, 3, 6, 9, and 12 days.

Chemical disinfection of duck hepatitis B virus: a model for inactivation of infectivity of hepatitis B virus.

The susceptibility of duck hepatitis B virus (DHBV) to the virucidal effects of sodium hypochlorite (NaOCl) and sodium dichloroisocyanurate (NaDCC) was compared to hepatitis B virus (HBV) with the aim of using the duck as a model for studying HBV disinfection. Using viral DNA polymerase (DNAP) as a target, inhibition of DNAP activity by chlorine disinfectants was found to be concentration-dependent but independent of contact time. Two minute exposure of minimal effective concentrations of sodium hypochlorite (domestic bleach: 3600 ppm and industrial bleach: 3180 ppm) and sodium dichloroisocyanurate (3000 ppm available chlorine) to DHBV- and HBV-rich plasma totally inhibited DNA polymerase activity.

Hepadnaviruses, their infections and hepatocellular carcinoma.

Ten years ago hepatitis B virus (HBV) was thought to be a unique virus, not included in any known family of viruses. Following the discovery of a number of HBV-like viruses that infect birds and mammals, the existence of a new family known as hepadnaviridae has been confirmed. Hepadnaviruses are small hepatotropic viruses that have a characteristic partially double stranded genome, exhibit a narrow host range and replicate by reverse transcription.

[Retrospective seroepidemiology of HIV-1].

Serum samples collected between 1974 and 1980 out of populations from the States of Pará and Goiás, Brazil, were tested for antibodies against HIV-1 through ELISA, immunofluorescence, and immunoblot. The aim was to describe the possibility of the virus presence in this country before the present epidemic. Four samples from an epidemiologically closed community, the Xicrin indians, gave positive reaction in the ELISA test, but were negative in the confirmatory tests.

The complete nucleotide sequence of the genome of a hepatitis B virus isolated from a naturally infected chimpanzee.

The complete nucleotide sequence of a strain of hepatitis B virus, originally isolated from a naturally infected chimpanzee, has been determined. Interesting features of the sequence include the presence of an in-phase stop codon in the 'pre-core' region of the core antigen open reading frame. The sequence shows approximately 10% nucleotide divergence from all of the other hepatitis B virus sequences previously published and the possibility that this divergence is the result of passage through chimpanzees is discussed.

Restriction of sensitivity of HIV-1-antigen ELISA by serum anti-core antibodies.

Addition of varying concentrations of HIV-1-seropositive plasma to purified virus particles and soluble viral antigen preparation inhibited the detection of HIV-1-antigen by ELISA. The degree of inhibition on p24 antigen ELISA depended on the relative concentrations of viral antigen and anti-p24 antibodies in the mixtures. The relevance of these observations to clinical specimens was demonstrated when serial plasma samples from nine AIDS-related complex (ARC) patients in a clinical trial of foscarnet therapy were assayed for p24 antigen.

Suramin treatment for chronic active hepatitis B--toxic and ineffective.

Suramin has recently been shown to inhibit the activity of the duck hepatitis B virus DNA polymerase (DHBV DNAp) in vitro. However, we found no demonstrable in vivo suppression of human hepatitis B virus DNA polymerase (HBV DNAp) activity in three male patients with severe chronic active hepatitis. Suramin treatment resulted in prolongation of the prothrombin time in all cases and a rise in bilirubin in two and it may have led to haemorrhage from oesophageal varices in one patient and to hepatic encephalopathy in another.

Antiviral activity of the polybasic anion, suramin and acyclovir in Hepadna virus infection.

Acyclovir and suramin were examined for their efficacy alone and in combination against duck hepatitis B virus (DHBV) in persistently infected Pekin ducks. In ducks the peak plasma concentration of acyclovir was reached thirty minutes after oral administration. Oral acyclovir and suramin administered intravenously suppressed the replication and production of infectious virions as measured by marked reduction of DNA polymerase activity during treatment.

Maternal transmission of duck hepatitis B virus in pedigree Pekin ducks.

A 14-month old female Pekin duck experimentally infected as an embryo with duck hepatitis B virus via the amniotic route has been a chronic carrier of duck hepatitis B virus with very high (P/N) values of DNA polymerase activity since hatching. All the progeny were, on evaluation for congenital infection, found to be duck hepatitis B virus positive by endogenous DNA polymerase reaction and electron microscopy. These offspring remained persistently viremic throughout the study.

Studies by electron microscopy on the assembly of duck hepatitis B virus in the liver.

Liver specimens from 1-day-old ducklings infected in ovo with maternally transmitted duck hepatitis B virus (DHBV) were examined by electron microscopy. Complete and incomplete DHBV particles were located within hypertrophied cisternae of the endoplasmic reticulum of the hepatocytes. The complete viral particles found intracellularly have inner cores with a diameter ranging from 35 to 37.

Experimental in ovo transmission of duck hepatitis B virus.

Inoculation of fertile Pekin duck eggs with diluted serum containing DHBV into eggs incubated for 24 h and into the extra-embryonic cavities of 14-day-old embryos resulted in a high proportion of viraemic ducklings irrespective of the route of inoculation. Long-term observation of som of the ducks established that the viraemia induced experimentally is long-lasting and has persisted for periods up to 16 mth post-hatch. Separation of DHBV from the plasma of carrier ducks by rate zonal centrifugation was examined by DNA polymerase (DNAP) activity.

Suramin inhibits duck hepatitis B virus DNA polymerase activity.

Suramin, a polybasic anion, blocks the activity of the DNA polymerase encoded by the duck hepatitis B virus. The interaction with the virus was studied under conditions in which the property of the drug to bind with proteins was used with plasma obtained from infected ducks with viraemia. Inhibition of DNA polymerase activity associated with core particles from infected liver and circulating virions is irreversible, occurs in a dose-response fashion and suggests that inhibition results from suramin-virus interaction.

Acute hepatitis A infection in hepatitis B chimpanzee carriers.

Two hepatitis B virus carrier chimpanzees which were superinfected with hepatitis A virus developed acute hepatitis followed by the production of antibodies to hepatitis A virus. The Southern blot technique employed to monitor liver hepatitis B virus DNA revealed that the amount of viral DNA in both animals was significantly reduced during the acute phase of hepatitis A infection. The levels of plasma hepatitis B DNA polymerase activity were also reduced in one chimpanzee.

The mechanism of replication of hepatitis B virus: evidence of asymmetric replication of the two DNA strands.

In this study we have characterised the DNA replicative intermediates of hepatitis B virus and have shown that HBV-DNA replication is asymmetric. This pattern of HBV replication is similar to that reported for the related duck hepatitis virus (DHBV) and suggests the involvement of a similar reverse transcription process in HBV-DNA replication.

A new method for detecting hepatitis B surface antigen in liver by silver staining.

Staining of tubular and circular structures within the cisternae of the endoplasmic reticulum of the cytoplasm of liver cells infected with hepatitis B virus was enhanced by the use of 1% aqueous silver proteinate.

Assay of HBV DNA in the plasma of HBV-carrier chimpanzees superinfected with non-A, non-B hepatitis.

A dot hybridisation technique was used to monitor the levels of hepatitis B virus (HBV) DNA in the plasma of two HBV-carrier chimpanzees which had been inocula ed with documented infectious non-A, non-B hepatitis agents. A marked decrease in the quantity of HBV DNA in the plasma during the acute phase of the non-A, non-B hepatitis was observed in both carriers. The possible role of interferon or a similar antiviral agent in modulation of the HBV-carrier state is discussed.

Non-A, non-B hepatitis in persistent carriers of hepatitis B virus.

There are reports in the literature that infection with hepatitis A virus in hepatitis B carriers can result in resolution of the carrier state. In an attempt to induce clearance of the carrier state of hepatitis B virus in two persistently infected chimpanzees, the chimpanzees were infused with documented non-A, non-B infectious material. Biochemical and histopathological evidence of hepatitis was accompanied by the unique abnormalities of endoplasmic reticulum associated with non-A, non-B hepatitis in the chimpanzees.

A study of ultrastructural alterations in experimental non-A, non-B hepatitis by electron-beam analysis.

An electron-beam X-ray microanalysis was carried out on sections of liver biopsy specimens obtained from chimpanzees infected with non-A, non-B hepatitis. The microanalysis was concentrated over areas where typical derangement of the endoplasmic reticulum, with the formation of tubular forms possessing walls with electron-dense central membrane, was visualized. These tubular structures are regarded as the most notable pathological alteration in affected hepatocytes.

Application of electron microscopy to the study of structural changes in the liver in non-A, non-B hepatitis.

Ultrastructural studies employing techniques such as alternative electron metal stain, high-angle tilting and high-voltage electron microscopy were carried out on liver biopsies obtained from chimpanzees infected with non-A, non-B hepatitis. Typical derangement of the endoplasmic reticulum leading to the formation of tubular structures in hepatocytes was observed. The use of potassium permanganate as an alternative stain revealed two features which have not been previously described.

Analysis of hepatitis virus DNA in the liver and serum of HBe antigen positive chimpanzee carriers.

Hepatitis B viral DNA present in the liver of HBe antigen positive chimpanzee carriers is in the form of viral molecules (3.2 Kb) and no integration into host DNA was observed. The 3.

Examination of crystalline arrays in non-A, non-B hepatitis.

Individual patients within crystalline arrays found in the endothelial cells of hepatic sinusoids in experimental non-A, non-B hepatitis were examined by the Markham rotation technique. The particles appeared to possess an outer structure with 16-18 divisions. The presence of the crystalline structures is probably a reflection of host cell response to infection.