Transfer Of Hepatitis Research Articles

Genomic characterization of hepatitis C virus transmitted founder variants with deep sequencing

Transfer of hepatitis C virus (HCV) infection from a donor to a new recipient is associated with a bottleneck of genetic diversity in the transmitted viral variants. Existing data suggests that one, or very few, variants emerge from this bottleneck to establish the infection (transmitted founder [T/F] variants). In HCV, very few T/F variants have been characterized due to the challenges of obtaining early infection samples and of high throughput viral genome sequencing.This study used a large, acute HCV, deep-sequenced dataset from first viremia samples collected in nine prospective cohorts across four countries, to estimate the prevalence of single T/F viruses, and to identify host and virus-related factors associated with infections initiated by a single T/F variant. The short reads generated by Illumina sequencing were used to reconstruct viral haplotypes with two haplotype reconstruction algorithms. The haplotypes were examined for random mutations (Poisson distribution) and a star-like phylogeny to identify T/F viruses. The findings were cross-validated by haplotype reconstructions across three regions of the genome (Core-E2, NS3, NS5A) to minimize the possibility of spurious overestimation of single T/F variants.Of 190 acute infection samples examined, 54 were very early acute infections (HCV antibody negative, RNA positive), and single transmitted founders were identified in 14 (26%, 95% CI: 16–39%) after cross validation across multiple regions of the genome with two haplotype reconstruction algorithms. The presence of a single T/F virus was not associated with any host or virus-related factors, notably viral genotype or spontaneous clearance.In conclusion, approximately one in four new HCV infections originates from a single T/F virus. Resolution of genomic sequences of single T/F variants is the first step in exploring unique properties of these variants in the infection of host hepatocytes.

Guidelines for the screening and follow-up of infants born to anti-HCV positive mothers.

Hepatitis C virus infection in infancy largely depends on vertical transmission. The transfer of hepatitis C virus from mother to child is almost invariably restricted to children whose mother is viremic, and the rate of transmission seems to be influenced by maternal virus load, although, in the single patient, the levels of viremia cannot be used as predictors of pediatric infection. In fact, the flow-chart for screening children at risk for vertically transmitted hepatitis C virus infection takes into account maternal viremia. In children born to anti-hepatitis C virus antibody positive, hepatitis C virus-RNA negative mothers, alanine aminotransferase and anti-hepatitis C virus should be investigated at 18-24 months of life. If alanine aminotransferase values are normal and anti-hepatitis C virus is undetectable, follow-up should be interrupted. In children born to hepatitis C virus-RNA positive mothers, alanine aminotransferase and hepatitis C virus RNA should be investigated at 3 months of age: (1) hepatitis C virus-RNA positive children should be considered infected if viremia is confirmed by a second assay performed within the 12th month; (2) hepatitis C virus-RNA negative children with abnormal alanine aminotransferase should be tested again for viremia at 6-12 months, and for anti-hepatitis C virus at 18 months; (3) hepatitis C virus-RNA negative children with normal alanine aminotransferase should be tested for anti-hepatitis C virus and alanine aminotransferase at 18-24 months, and should be considered non-infected if alanine aminotransferase is normal and anti-hepatitis C virus undetectable; (4) anti-hepatitis C virus seropositivity beyond the 18th month in a never-viremic child with normal alanine aminotransferase is likely consistent with past hepatitis C virus infection.

Adoptive transfer of HBV immunity by kidney transplantation and the effect of postoperative vaccination

Transfer of hepatitis B immunity occurs upon the transfer of immunologically active cells from the donor to the recipient by means of an organ graft. This has been repeatedly demonstrated for bone marrow and liver transplantations. Evidence is now presented for the transfer of anti-hepatitis B surface antibodies (anti-HBs) after kidney transplantation in rats. Kidney donors from one syngeneic and two allogeneic rat strains were immunized twice with 4 μg of recombinant hepatitis B vaccine. In week 6 after the first vaccination, kidney grafts were transplanted into Lewis (LEW) rats. Half of the recipients underwent daily immunosuppressive treatment with cyclosporin A (CsA). All recipients were vaccinated either after 10 weeks or 1 week postoperatively. Anti-HBs titer was measured weekly. Effective anti-HBs titers (10–227 mIU/ml, lasting for 1–7 weeks) were detected in 86% (25/29) of recipient rats, whose corresponding donors all had a titer above 15,000 mIU/ml. Immunosuppression enhanced the donor-derived immunity in terms of recipient-to-donor titer ratio, maximal titer and titer persistence.

Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen

Impaired T-cell reactivity is believed to be the dominant cause of chronic hepatitis B virus (HBV) infection. We characterized HBV-specific T-cell responses in chronic hepatitis B surface antigen carriers who received bone marrow from HLA-identical donors with natural immunity to HBV and seroconverted to antibody to hepatitis B surface antigen. T-cell reactivity to HBV antigens and peptides was assessed in a proliferation assay, the frequency of HBV core- and surface-specific T cells was quantified directly by ELISPOT assays, and T-cell subsets were analyzed by flow cytometry. CD4+ T-cell reactivity to HBV core was common in bone marrow donors and the corresponding recipients after hepatitis B surface antigen clearance, whereas none reacted to surface, pre-S1, or pre-S2 antigens. Furthermore, CD4+ T cells from donor/recipient pairs recognized similar epitopes on hepatitis B core antigen; using polymerase chain reaction for the Y chromosome, the recipients' CD4+ T lymphocytes were confirmed to be of donor origin. The frequency of core-specific CD4+ and CD8+ T cells was several-fold higher than those specific for surface antigen. This study provides the first evidence in humans that transfer of hepatitis B core antigen-reactive T cells is associated with resolution of chronic HBV infection. Therapeutic immunization with HBV core gene or protein deserves further investigation in patients with chronic hepatitis B.

Foodborne viruses and fresh produce.

Raw and minimally processed fruits and vegetables are typically sold to the consumer in a ready-to-use or ready-to-eat form. These products do not generally contain preservatives or antimicrobial agents and rarely undergo any heat processing prior to consumption. For many years raw fruits and vegetables have been implicated as vehicles for transmission of infectious micro-organisms. Although fresh produce can support the growth and/or survival of many pathogenic bacteria there is little published information on the stability of human pathogenic viruses on these food products. Viruses cannot grow in or on foods but may sometimes be present on fresh produce as a result of faecal contamination. This contamination can arise at source in the growth and harvesting area from contact with polluted water and inadequately or untreated sewage sludge used for irrigation and fertilization. Alternatively, fruits or vegetables handled by an infected person might become contaminated with virus and transmit infection. The most frequently reported foodborne viral infections are viral gastroenteritis and hepatitis A: both have been associated with the consumption of fresh fruit or vegetables.

Transfer of hepatitis B virus genome by adenovirus vectors into cultured cells and mice: crossing the species barrier.

For the study of hepatitis B virus infection, no permissive cell line or small animal is available. Stably transfected cell lines and transgenic mice which contain hepadnavirus genomes produce virus, but--unlike in natural infection--from an integrated viral transcription template. To transfer hepadnavirus genomes across the species barrier, we developed adenovirus vectors in which 1.3-fold-overlength human and duck hepatitis B virus genomes were inserted. The adenovirus-mediated genome transfer efficiently initiated hepadnavirus replication from an extrachromosomal template in established cell lines, in primary hepatocytes from various species, and in the livers of mice. Following the transfer, hepatitis B virus proteins, genomic RNA, and all replicative DNA intermediates were detected. Detection of covalently closed circular DNA in hepatoma cell lines and in primary hepatocytes indicated that an intracellular replication cycle independent from the transferred linear viral genome was established. High-titer hepatitis B virions were released into the culture medium of hepatoma cells and the various primary hepatocytes. In addition, infectious virions were secreted into the sera of mice. In conclusion, adenovirus-mediated genome transfer initiated efficient hepatitis B virus replication in cultured liver cells and in the experimental animals from an extrachromosomal template. This will allow development of small-animal systems of hepatitis B virus infection and will facilitate study of pathogenicity of wild-type and mutant viruses as well as of virus-host interaction and new therapeutic approaches.

Australians investigate hepatitis C cases

Infection control procedures in Australia are under renewed scrutiny as health authorities investigate the possibility that patient to patient transfer of hepatitis C may occur. The New South Wales (NSW) health department fears that five patients contracted the disease after visiting a private hospital in Sydney on the same day in January last year. Federal health minister Carmen Lawrence has warned that …

Transfer of hepatitis B virus by contaminated reusable needle electrodes after electrodesiccation in simulated use

Reusable needle electrodes have been standard for electrodesiccation procedures commonly done by dermatologists. This study investigates the risk of transmission of hepatitis B virus by such electrodes during simulated use with electrodesiccation. Sterile needle electrodes were inoculated with either purified hepatitis B surface antigen (HBsAg+) concentrate or serum positive for both HBsAg and deoxyribonucleic acid (DNA) polymerase activity (a measure of infectious and replicating hepatitis B virus), followed by simulated use for electrodesiccation at various settings and rinsing of the tip with negative serum. The rinse serum was then assayed for HBsAg, DNA polymerase activity, and the presence of viral particles by electron microscopy. HBsAg could be transferred through the electrodesiccation procedure at all settings used. Although DNA polymerase activity was negative in the rinse serum, electron microscopy demonstrated transfer of HBsAg forms and complete virus. These results suggest a potential risk of spread of hepatitis B virus by reusable needle electrodes for electrodesiccation.