title: A novel hepacivirus with an unusually long and intrinsically disordered NS5A protein in a wild Old World primate.
abstract: GB virus B (GBV-B; family Flaviviridae, genus Hepacivirus) has been studied in New World primates as a model for human hepatitis C virus infection, but the distribution of GBV-B and its relatives in nature has remained obscure. Here, we report the discovery of a novel and highly divergent GBV-B-like virus in an Old World monkey, the black-and-white colobus (Colobus guereza), in Uganda. The new virus, guereza hepacivirus (GHV), clusters phylogenetically with GBV-B and recently described hepaciviruses infecting African bats and North American rodents, and it shows evidence of ancient recombination with these other hepaciviruses. Direct sequencing of reverse-transcribed RNA from blood plasma from three of nine colobus monkeys yielded near-complete GHV genomes, comprising two distinct viral variants. The viruses contain an exceptionally long nonstructural 5A (NS5A) gene, approximately half of which codes for a protein with no discernible homology to known proteins. Computational structure-based analyses indicate that the amino terminus of the GHV NS5A protein may serve a zinc-binding function, similar to the NS5A of other viruses within the family Flaviviridae. However, the 521-amino-acid carboxy terminus is intrinsically disordered, reflecting an unusual degree of structural plasticity and polyfunctionality. These findings shed new light on the natural history and evolution of the hepaciviruses and on the extent of structural variation within the Flaviviridae.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lauck
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Sibley
authors.forename: James
authors.initials: J
authors.lastname: Lara
authors.forename: Michael A
authors.initials: MA
authors.lastname: Purdy
authors.forename: Yury
authors.initials: Y
authors.lastname: Khudyakov
authors.forename: David
authors.initials: D
authors.lastname: Hyeroba
authors.forename: Alex
authors.initials: A
authors.lastname: Tumukunde
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Weny
authors.forename: William M
authors.initials: WM
authors.lastname: Switzer
authors.forename: Colin A
authors.initials: CA
authors.lastname: Chapman
authors.forename: Austin L
authors.initials: AL
authors.lastname: Hughes
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Tony L
authors.initials: TL
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D003104:Colobus; D003198:Computer Simulation; D029406:GB virus B / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification*; D016679:Genome, Viral; D006526:Hepatitis C / Q000662:veterinary* / Q000821:virology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D018419:Primate Diseases / Q000821:virology*; D011487:Protein Conformation; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D014454:Uganda; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase