title: Whole-genome analysis of genetic recombination  of hepatitis delta virus: molecular domain in delta  antigen determining trans-activating efficiency.
abstract: Hepatitis delta virus (HDV) is the only animal RNA virus that has an unbranched rod-like genome with ribozyme activity and is replicated by host RNA polymerase. HDV RNA recombination was previously demonstrated in patients and in cultured cells by analysis of a region corresponding to the C terminus of the delta antigen (HDAg), the only viral-encoded protein. Here, a whole-genome recombination map of HDV was constructed using an experimental system in which two HDV-1 sequences were co-transfected into cultured cells and the recombinants were analysed by sequencing of cloned reverse transcription-PCR products. Fifty homologous recombinants with 60 crossovers mapping to 22 junctions were identified from 200 analysed clones. Small HDAg chimeras harbouring a junction newly detected in the recombination map were then constructed. The results further indicated that the genome-replication level of HDV was sensitive to the sixth amino acid within the N-terminal 22 aa of HDAg. Therefore, the recombination map established in this study provided a tool for not only understanding HDV RNA recombination, but also elucidating the related mechanisms, such as molecular elements responsible for the trans-activation levels of the small HDAg.
authors.affiliation: Division of Microbiology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan.|Department of Microbiology and Immunology, Chang Gung University, Guishan, Taoyuan 33302, Taiwan.
authors.forename: Mei
authors.initials: M
authors.lastname: Chao
authors.affiliation: Division of Microbiology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of Microbiology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan.
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Lin
authors.affiliation: Division of Microbiology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan 33302, Taiwan.|Department of Microbiology and Immunology, Chang Gung University, Guishan, Taoyuan 33302, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan 33302, Taiwan.
authors.forename: Hsin-Pai
authors.initials: HP
authors.lastname: Li
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Guishan, Taoyuan 33302, Taiwan.
authors.forename: Shan-Bei
authors.initials: SB
authors.lastname: Iang
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D016679:Genome, Viral; D055106:Genome-Wide Association Study; D005838:Genotype; D003698:Hepatitis Delta Virus / Q000235:genetics* / Q000276:immunology; D008957:Models, Genetic; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics*; D011995:Recombination, Genetic; D015533:Transcriptional Activation; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D012367:RNA, Viral