title: Conserved transactivating and pro-apoptotic functions of hepadnaviral X protein in ortho- and avihepadnaviruses.
abstract: Two established activities of the multifunctional human hepatitis B virus X-protein are its transactivating and pro-apoptotic potential. We analysed whether X-proteins from other orthohepadnaviruses and the newly discovered avihepadnaviral X-proteins have similar functions as HBx. Previously, we have shown that HBx suppresses oncogenic transformation of primary rat embryo fibroblasts (REF) by induction of apoptosis. Using this system, we found that the wildtype X-proteins of woodchuck, ground squirrel, arctic squirrel and woolly monkey hepatitis B virus exhibit similar levels of pro-apoptotic activity as HBx, whereas mutants with carboxyterminal deletions were severely impaired in this activity. A strong correlation between the pro-apoptotic and transactivating abilities of the mammalian X-proteins was found. The newly discovered avihepadnaviral X-like proteins showed similar and Raf-MAPK pathway-dependent transactivating abilities and induced apoptosis in the REF-assay. Our data indicate that the transactivating and pro-apoptotic activities reside in the carboxyterminal half of orthohepadnaviral X and are conserved in avihepadnaviral X-proteins.
authors.affiliation: Institute for Medical Virology, JLU Giessen, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Schuster
authors.forename: Eberhardt
authors.initials: E
authors.lastname: Hildt
authors.forename: Shau-Feng
authors.initials: SF
authors.lastname: Chang
authors.forename: Olivier
authors.initials: O
authors.lastname: Terradillos
authors.forename: Teresa
authors.initials: T
authors.lastname: Pollicino
authors.forename: Robert
authors.initials: R
authors.lastname: Lanford
authors.forename: Wolfram H
authors.initials: WH
authors.lastname: Gerlich
authors.forename: Hans
authors.initials: H
authors.lastname: Will
authors.forename: Stephan
authors.initials: S
authors.lastname: Schaefer
mesh_terms: D000818:Animals; D017209:Apoptosis; D015613:Hepadnaviridae / Q000737:chemistry* / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D015534:Trans-Activators; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein