title: A chimeric GB virus B encoding the hepatitis C virus hypervariable region 1 is infectious in vivo.
abstract: Two GB virus B (GBV-B) chimeric genomes, GBV-HVR and GBV-HVRh (with a hinge), containing the coding region of the immunodominant hypervariable region 1 (HVR1) of the E2 envelope protein of Hepatitis C virus (HCV) were constructed. Immunoblot analysis confirmed that HVR1 was anchored to the GBV-B E2 protein. To investigate the replication competence and in vivo stability of in vitro-generated chimeric RNA transcripts, two naïve marmosets were inoculated intrahepatically with the transcripts. The GBV-HVR chimeric genome was detectable for 2 weeks post-inoculation (p.i.), whereas GBV-HVRh reverted to wild type 1 week p.i. Sequencing analysis of the HVR1 and flanking regions from GBV-HVR RNA isolated from marmoset serum demonstrated that the HVR1 insert remained unaltered in the GBV-HVR chimera for 2 weeks. Inoculation of a naïve marmoset with serum collected at 1 week p.i. also resulted in viraemia and confirmed that the serum contained infectious particles. All animals cleared the infection by 3 weeks p.i. and remained negative for the remaining weeks. The chimera may prove useful for the in vivo examination of any HCV HVR1-based vaccine candidates.
authors.affiliation: The Macfarlane Burnet Institute, GPO Box 2284, Melbourne, VIC 3001, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Haqshenas
authors.affiliation: Department of Microbiology, Monash University, Clayton, VIC 3800, Australia.|The Macfarlane Burnet Institute, GPO Box 2284, Melbourne, VIC 3001, Australia.
authors.forename: X
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Microbiology, Monash University, Clayton, VIC 3800, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Netter
authors.affiliation: Department of Medicine (RMH/WH), University of Melbourne, Centre for Clinical Research Excellence, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Torresi
authors.affiliation: Department of Microbiology, Monash University, Clayton, VIC 3800, Australia.|The Macfarlane Burnet Institute, GPO Box 2284, Melbourne, VIC 3001, Australia.
authors.forename: E J
authors.initials: EJ
authors.lastname: Gowans
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002144:Callithrix; D005260:Female; D018178:Flaviviridae Infections / Q000821:virology; D029406:GB virus B / Q000235:genetics* / Q000254:growth & development*; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D015151:Immunoblotting; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D044967:Serum / Q000821:virology; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics*; D014766:Viremia
chemical_list: C400562:HVR1 protein, Hepatitis C virus; D012367:RNA, Viral; D014764:Viral Proteins