The objectives of this proposal are to (a) further characterize the polypeptide(s) and corresponding antibodies associated with the hepadnavirus X and polymerase gene products in infected sera and liver tissues from humans, woodchucks and ducks and (b) to provide clinically useful reagents for the evaluation of these markers in virus infected patients and animals. The approach used to obtain antibody probes known or likely to cross-react with analogous gene products among hepadnaviruses will be to select and synthesize peptides deduced from different regions of the hepatitis B virus (HBV) genome which are hydrophilic and share primary sequence homology with the analogous regions in the other hepadnaviruses. X antibodies will be used to screen infected liver tissue sections from animals with acute hepatitis, chronic hepatitis and hepatocellular carcinoma to determine the frequency and distribution of X determinants throughout the course of infection and to compare these patterns of expression with those of other known virus gene products. The availability of X and polymerase antibodies will provide probes to assay for specifically reactive polypeptides in infected liver tissue homogenates and subviral particles. The latter particles include cytoplasmic replication complexes (containing DNA/RNA hybrids), nuclear nucleoprotein complexes (containing supercoiled DNA), liver or virion derived nucleocapsid or core particles, and complexes of a protein covalently attached to the 5' end of the coding strand of viral DNA. Using the synthetic peptides made from the X and polymerase regions of HBV, the frequency and distribution of corresponding antibodies in infection will be determined in a number of human an woodchuck populations. The presence of these antibodies in single and serial bleedings form acutely infected individuals will be assayed to test the hypothesis that these are early markers of infection which may have diagnostic and prognostic significance. Screening of patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma will determine the relationship between these newly defined markers, other markers of infection, and disease outcome. Non-A, non-B sera will also be screened for the presence of these antibodies, especially where such sera may contain only anti-HBc, to test the hypothesis that X and/or these antibodies specificities will be constructed which may have clinical value in determining the significance of these markers in infection and treatment.
| Schinazi, Raymond F; Bassit, Leda; Clayton, Marcia M et al. (2012) Evaluation of single and combination therapies with tenofovir disoproxil fumarate and emtricitabine in vitro and in a robust mouse model supporting high levels of hepatitis B virus replication. Antimicrob Agents Chemother 56:6186-91 |
