Effects of HBV and HDV Antigens on the Development of Caenorhabditis elegans

Canorhabditis elegans, a soil free-living nematode, is a well-established model system for wide spectra of life science research, such as neural biology, developmental biology and cell biology, physiology, and animal behavior because of non-pathogenic, short-live cycle (3.5 days), easy handle and low cost. In contrast, using C. elegans as a model system for investigating virus- and bacteria-host cell interaction is just in an infant stage. We have been studied hepatitis B and D viruses for more than two decades, however, many unanswered questions remain, i.e., cross-talk between HDV and HBV. Therefore, in this three-year grant proposal, we like to explore new research frontier by introducing viral genes into C. elegans to answer those unclear molecular biology questions. The rationales are followings: 1) the effect of viral genes on worms can be analyzed in wider aspects, such as on worm development and growth and cell differentiation and death, than hepatoma or mammalian cell lines which we largely use, 2) the genome of C. elegans is completely sequenced and many genetic background mutants are available, and 3) the RNAi system is easily to knock down certain gene in worms for studying the role of corresponding protein in HBV and HDV cross-talk. Less than a year, we have created transgenic worms expressing HDV large antigen and HBV surface antigen by microinjection. Exciting phenotypes of transgenic worms have been observed. Therefore, in this proposal, the following aims are proposed. (1) To investigate the mechanism of developmental retardation in transgenic worms bearing HDV and HBV antigens. (2) To establish more worms expressing large, middle, and major surface antigens (LHBsAg, MHBsAg, and SHBsAg) and to examine their effect on worm growth and development. (3) To cross SHBsAg expression worm to those containing LDAg or SDAg to examine whether subviral empty particles can be produced. (4) To use different genetic background worms or the RNAi method to elucidate the molecules involving in signaling transduction regulating LDAg and SHBsAg for subviral particle formation. By the end of this project, we hope to elucidate how HBV and HDV interaction, furthermore, to provide more detail and new mechanisms regarding how both HBV and HDV viral antigens cause cell pathogenesis.

Project ID:PC9801-2141
External Project ID:NSC97-2320-B182-002-MY3