Journal of General Virology (2011), 92, 233–246 DOI 10.1099/vir.0.027490-0 Review Correspondence Jack T. Stapleton jack-stapleton@uiowa.edu The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae Jack T. Stapleton,1 Steven Foung,2 A. Scott Muerhoff,3 Jens Bukh4,5 and Peter Simmonds5 1Department of Internal Medicine, Veterans Administration Medical Center and the University of Iowa, Iowa City, IA, USA 2Department of Pathology, Stanford University, Stanford, CA, USA 3Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL, USA 4Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark, and Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Denmark 5Centre for Infectious Diseases, University of Edinburgh, Edinburgh, UK In 1967, it was reported that experimental inoculation of serum from a surgeon (G.B.) with acute hepatitis into tamarins resulted in hepatitis. In 1995, two new members of the family Flaviviridae, named GBV-A and GBV-B, were identified in tamarins that developed hepatitis following inoculation with the 11th GB passage. Neither virus infects humans, and a number of GBV-A variants were identified in wild New World monkeys that were captured. Subsequently, a related human virus was identified [named GBV-C or hepatitis G virus (HGV)], and recently a more distantly related virus (named GBV-D) was discovered in bats. Only GBV-B, a second species within the genus Hepacivirus (type species hepatitis C virus), has been shown to cause hepatitis; it causes acute hepatitis in experimentally infected tamarins. The other GB viruses have however not been assigned to a genus within the family Flaviviridae. Based on phylogenetic relationships, genome organization and pathogenic features of the GB viruses, we propose to classify GBV-A- like viruses, GBV-C and GBV-D as members of a fourth genus in the family Flaviviridae, named Pegivirus (pe, persistent; g, GB or G). We also propose renaming ‘GB’ viruses within the tentative genus Pegivirus to reflect their host origin. Introduction The International Committee on Taxonomy of Viruses (ICTV) provides guidelines for virus nomenclature and classification based on orders (-virales), families (-viridae), subfamilies (virinae), genera (-virus) and species (The Universal Virus Database of the International Committee on Taxonomy of Viruses; http://www.ncbi.nlm.nih.gov/ ICTVdb/index.htm). A species is a ‘polythetic class of viruses that constitutes a replicating lineage and occupies a particular ecological niche’. Several properties must be present to differentiate individual species, including differences in genome sequences, host range, cell and tissue tropism, pathogenicity or cytopathology, physical properties and antigenic properties. Within the family Flaviviridae, the ICTV has classified hepatitis C virus (HCV) as the type species within the genus Hepacivirus, Supplementary figures are available with the online version of this paper. 027490 Printed in Great Britain and GB virus B (GBV-B) has tentatively been assigned as a second species within this genus (http://www.ncbi.nlm.nih. gov/ICTVdb/index.htm). The related GBV-A and GBV-A- like agents, and GBV-C (or hepatitis G virus; HGV) viruses have also been assigned to the family Flaviviridae, but not to a genus (http://www.ncbi.nlm.nih.gov/ICTVdb/index.htm). A related virus was recently discovered in Old World frugivo- rous bats (Pteropus giganteus) and was termed GBV-D (Epstein et al., 2010). In this review, we propose to assign GBV-A, GBV-C/HGV and GBV-D as species within a new genus, Pegivirus. In addition, we suggest that the GB viruses within this fourth genus of the family Flaviviridae be renamed to reflect better their biological and pathogenic properties. History Following the discovery of hepatitis A virus (HAV) and hepatitis B virus (HBV) in the 1960s and 1970s, it became 233