Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family Smith, Donald B.; Becher, Paul; Bukh, Jens; Gould, Ernest A.; Meyers, Gregor; Monath, Thomas; Muerhoff, A. Scott; Pletnev, Alexander; Rico-Hesse, Rebecca; Stapleton, Jack T.; Simmonds, Peter Published in: Journal of General Virology DOI: 10.1099/jgv.0.000612 Publication date: 2016 Document version Publisher's PDF, also known as Version of record Document license: CC BY Citation for published version (APA): Smith, D. B., Becher, P., Bukh, J., Gould, E. A., Meyers, G., Monath, T., Muerhoff, A. S., Pletnev, A., Rico- Hesse, R., Stapleton, J. T., & Simmonds, P. (2016). Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family. Journal of General Virology, 97, 2894-2907. https://doi.org/10.1099/jgv.0.000612 Download date: 28. sep.. 2021 Journal of General Virology (2016), 97, 2894–2907 DOI 10.1099/jgv.0.000612 Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family Donald B. Smith,1 Paul Becher,2 Jens Bukh,3,4 Ernest A. Gould,5 Gregor Meyers,6 Thomas Monath,7,8 A. Scott Muerhoff,9 Alexander Pletnev,10 Rebecca Rico-Hesse,11,12 Jack T. Stapleton13,14,15 and Peter Simmonds1,16 Correspondence 1Centre for Immunity, Infection and Evolution, University of Edinburgh, Scotland, UK Donald B. Smith 2Institute of Virology, University of Veterinary Medicine, Hannover, Germany [email protected] 3 or Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark [email protected] 4Copenhagen Hepatitis C Program (CO-HEP), Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark 5EHESP French School of Public Health, French Institute of Research for Development (IRD), Aix Marseille Universite, EPV UMR_D 190 Emergence des Pathologies Virales, Marseille, France 6Institut für Immunologie, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany 7Hookipa Biotech AG, Vienna, Austria 8PaxVax Inc., Menlo Park and Redwood City, CA, USA 9Abbott Diagnostics Research and Development, Abbott Park, IL, USA 10Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA 11Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA 12Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA 13Medical Service, Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA 14Department of Internal Medicine, University of Iowa, Iowa City, IA, USA 15Department of Microbiology, University of Iowa, Iowa City, IA, USA 16Nuffield Department of Medicine, University of Oxford, Oxford, UK Proposals are described for the assignment of recently reported viruses, infecting rodents, bats and other mammalian species, to new species within the Hepacivirus and Pegivirus genera (family Flaviviridae). Assignments into 14 Hepacivirus species (Hepacivirus A–N) and 11 Pegivirus species (Pegivirus A–K) are based on phylogenetic relationships and sequence distances between conserved regions extracted from complete coding sequences for members of each proposed taxon. We propose that the species Hepatitis C virus is renamed Hepacivirus C in order to acknowledge its unique historical position and so as to minimize confusion. Despite the newly documented genetic diversity of hepaciviruses and pegiviruses, members of these genera remain phylogenetically distinct, and differ in hepatotropism and the possession of a basic core protein; pegiviruses in general lack these features. However, other characteristics that were originally used to support their division into separate genera are no longer definitive; there Received 23 June 2016 is overlap between the two genera in the type of internal ribosomal entry site and the presence of ¢ Accepted 21 September 2016 miR-122 sites in the 5 UTR, the predicted number of N-linked glycosylation sites in the envelope E1 and E2 proteins, the presence of poly U tracts in the 3¢ UTR and the propensity of viruses to Downloaded from www.microbiologyresearch.org by 2894 000612 Printed in Great Britain IP: 130.225.178.2 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). On: Thu, 22 Dec 2016 10:50:47 Taxonomy of the Hepacivirus and Pegivirus genera establish a persistent infection. While all classified hepaciviruses and pegiviruses have mammalian hosts, the recent description of a hepaci-/pegi-like virus from a shark and the likely existence of further homologues in other non-mammalian species indicate that further species or genera remain to be defined in the future. INTRODUCTION two genera can be distinguished. We additionally describe proposals for the assignment of viruses for which a com- A recurrent feature of virus taxonomy is that as more infor- plete coding sequence is available into a series of species mation accumulates on the genetic diversity within estab- within the two genera and provide demarcation criteria that lished virus taxa such as species and genera, the discrete define these assignments. We propose the creation of 13 demarcation criteria originally applied to distinguish additional Hepacivirus species and 9 additional Pegivirus between them become blurred. species. Hepatitis C virus (HCV) has been the only named species within the genus Hepacivirus since the genus was created in 1996. Considerable diversity exists between different isolates RESULTS of HCV (Bukh et al., 1993; Simmonds et al., 1993), with 7 genotypes and 84 subtypes currently recognized (Smith Hepacivirus genus et al., 2014) (https://talk.ictvonline.org/ictv_wikis/flaviviri- Hepacivirus sequences were aligned using MUSCLE and dae/w/sg_flavi/56.hcv-classification). Despite this diversity, reduced to a set of those differing over their complete cod- all of these viruses are derived from human infections and ing sequence by amino acid p-distances greater than 0.1. are associated with acute and chronic liver disease, and Since different genotypes of HCV all differ by 0.23–0.31, there continues to be widespread agreement that they are this cut-off would be expected to include all variants likely most appropriately considered as members of a single spe- to represent different species. A scan of mean amino acid p- cies. A related virus, GBV-B was identified in 1995 from distance over the coding region revealed two regions where New World monkeys (Simons et al., 1995a) and is associ- p-distances were consistently less than 0.6: positions 1123– ated with acute liver disease, but remained unclassified. In 1566 and 2536–2959 (numbered relative to the Hepacivirus the last few years, several more divergent viruses have been type species, M62321 (Choo et al., 1989) (Fig. 1), and there- discovered with genome structures and conserved sequence fore most informative for phylogenetic comparisons. Phy- motifs that are similar to those of HCV and GBV-B and iso- logenies of Hepacivirus sequences in these regions were lated from a variety of host species including dog (Kapoor congruent apart from minor and non-bootstrap-supported et al., 2011), horse (Burbelo et al., 2012), bat (Quan et al., rearrangements of deep branches (Fig. 2a, b). For the region 2013), rodent (Drexler et al., 2013; Firth et al., 2014; 1123–1566, amino acid p-distances were greater than 0.3 Kapoor et al., 2013a), Old World monkey (Lauck et al., apart from distances between different genotypes of HCV, 2013) and cow (Baechlein et al., 2015; Corman et al., 2015). which were 0.12–0.19 (Fig. 2c). A more continuous distri- These viruses differ considerably in their epidemiology and bution of amino acid p-distances was observed for the presumed route of transmission from HCV. region 2536–2959, with discontinuities centred on distances of 0.35 and 0.45. Similarly, the Pegivirus (pronounced peh-gee virus) genus, when first proposed (Stapleton et al., 2011), comprised two Although evidence has been provided for recombination species: Pegivirus A, including the viruses GBV-A (Simons within (Gonzalez-Candelas et al., 2011) and between Hepa- et al., 1995a) and GBV-C (Leary et al., 1996; Linnen et al., civirus species (Theze et al., 2015), the only known recombi- 1996; Simons et al., 1995b) isolated from primates, and nant included in our dataset was the sequence KC796077 Pegivirus B, including viruses derived from bats (Epstein (Quan et al., 2013), which is the single known representa- et al., 2010). In the last few years, several papers have tive of its clade; exclusion of this sequence did not affect the described viruses that share many features with Pegivirus A distribution of sequence distances or phylogenetic relation- and Pegivirus B, but which are divergent in genome ships between the other species (data not shown). sequence and structure and infect humans (Berg et al., The phylogenetic relationships observed for these two 2015; Kapoor et al., 2015), bats (Quan et al., 2013), horses genome regions are consistent with the division of the Hep- (Chandriani et al., 2013; Kapoor et al., 2013b), rodents acivirus genus into 14 species which we propose should be (Firth et al., 2014; Kapoor et al., 2013a) and pigs (Baechlein named Hepacivirus A–N (Table 1). Although HCV was the et al., 2016). In addition, viruses similar to GBV-C have first Hepacivirus to be discovered and the type species of its been discovered in a range of primate species (Birkenmeyer genus, we have chosen to assign it to Hepacivirus C rather et al., 1998; Sibley et al., 2014). than Hepacivirus A so as to minimize the potential for con- In the current study, we review the classification of these fusion. To be clear, individual isolates of this virus will still two genera and have revised the list of features by which the be called hepatitis C virus (HCV), but they will all belong to Downloaded from www.microbiologyresearch.org by http://jgv.microbiologyresearch.org 2895 IP: 130.225.178.2 On: Thu, 22 Dec 2016 10:50:47 D.