Nomenclature of human rotaviruses: designation of subgroups and serotypes*

/Termninology /Terminologie Bulletint ofthe World Health Organization, 62 (3): 501-503 (1984) ©) World Health Organization 1984 Nomenclature of human rotaviruses: designation of subgroups and serotypes* Based on the specificity ofsubgroup antigens and serotype antigens which are situated, respectively, in the major inner and outer capsid polypeptides, a new nomenclature for human rotaviruses is proposed. The subgroups are designated as Iand II, and the serotypes as 1, 2, 3, 4. Soon after the discovery of the human rotaviruses, it was established that all those that were then known possessed a common "group" antigen situated in the inner capsid layer (1). Different "serotypes" of rota- viruses were first reported from Brussels, Belgium, and Birmingham, England, in 1978 (2,3). In Brussels they were distinguished by a complement fixation test and by immune electron microscopy, and later by enzyme-linked immunosorbent assay (ELISA) in both Brussels and Bethesda, USA (2, 4). In Bir- mingham they were distinguished by a neutralization test involving neutralization of immunofluorescent foci (NIFF) which measured the capacity of sera to neutralize the infection of tissue culture cells by virus obtained from human faeces. It was assumed that all assays detected the same or similar specificities, and hence the term "sero- type" was applied to the differences defined by these various assays. However, it was later found that certain animal viruses such as Nebraska Calf Diar- rhoea Virus (NCDV) and "O" virus reacted like members of the "serotype 1" of human rotavirus (5). * This note was prepared by the Steering Committee of the Scientific Working Group on Viral Diarrhoeas, WHO Programme for Diarrhoeal Diseases Control. The members of this Committee are P. A. Bachmann, Institute of Medical Microbiology, University of Munich, Munich, Federal Republic of Germany; R. F. Bishop, Department of Gastroenterology, Royal Children's Hospital, Park- ville, Victoria, Australia; T. H. Flewett, Regional Virus Laboratory, East Birmingham Hospital, Birmingham, England; A. Z. Kapikian, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; M. M. Mathan, Christian Medical College Hospital, Vellore, Tamil Nadu, India; and G. Zissis, Department of Medical Virology, H6pital St Pierre, Brussels, Belgium. A French translation of this note appears on pages 505-507. Requests for reprints should be sent to Diarrhoeal Diseases Control Programme, World Health Organization, 1211 Geneva 27, Switzer- land. This was surprising, since animal rotaviruses had been found to have neutralization specificities dif- ferent from those observed in human rotaviruses (1). This anomaly was resolved when it was found that the original "serotype" designation (2) was distinct from the neutralization specificity (5). Studies of re- assortant viruses eventually showed that these two specificities were coded for by different genes (6). It was then proposed that the specificity coded by the 6th gene should be referred to as the subgroup, and the neutralization specificity coded by the 9th gene (Wa virus) should be referred to as the serotype (5, 6). LOCATION OF SUBGROUP ANTIGENS AND SEROTYPE ANTIGENS It is now clear that the subgroup antigens are situated in the major inner capsid polypeptide of relative molecular mass about 46 000. This poly- peptide is a product of the 6th genomic segment and two serologically distinct subgroup antigens have been detected to date by ELISA or immune adherence haemagglutination. Antibodies directed against these subgroup polypeptides neutralize infectivity only feebly, if at all (8, 9). Monoclonal antibodies specific for each of these two subgroup antigens have been developed (7). Serotype antigens are situated in the major outer capsid polypeptide. This is a glycosylated polypeptide of relative molecular mass about 36 000. Neutraliz- ation is determined primarily by antibodies directed against the polypeptide, and in most strains it is a product of the 9th genomic segment. In some strains 4424 -501- 502 NOMENCLATURE OF HUMAN ROTAVIRUSES the segment may be in the 7th or 8th position as shown by polyacrylamide gel electrophoresis (10, 11). Sero- types are characteristically identified by neutraliz- ation of infectivity using plaque reduction assay, or fluorescent focus assay (12, 13). The criteria used for identifying new serotypes depend on the assay selected, and the sera used. A virus is defined as belonging to a new serotype if titration using hyper- immune sera in a plaque reduction assay shows a 20- fold reciprocal difference in titre between homo- logous and heterologous reactions (12). If convales- cent sera are used in a plaque reduction assay, or if fluorescent focus assays are used, then it may not be possible to demonstrate more than an 8-fold differ- ence between homologous and heterologous reactions (12, 13). THE PROPOSED NOMENCLATURE To avoid confusion in the literature, and in order to respect priority, the following system of nomeclature for strains of human rotaviruses is proposed: 1. Rotavirus subgroups should be designated by Roman numerals, i.e., I, II. 2. Rotavirus serotypes should be designated by Arabic numerals, i.e., 1, 2, 3, 4. Accordingly, human rotaviruses can be designated as follows: Representative human rotavirus strains Subgroup Serotype (12, 14-17) DS-1,S2,KUN I 2 Wa, K8, KU II I M, P, ITO, NEMOTO, YO II 3 ST4, HOCHI, HOSOKAWA II 4 Certain animal rotaviruses can be classified accord- ing to these designations, for example SA-l 1 virus reacts as serotype 3, subgroup I. NCDV reacts as subgroup I, but is distinct serotypically from the four human rotaviruses (18). Allocation of further serotype numbers should be made sequentially for human (and animal) rota- viruses that share the group antigen possessed by the viruses described above. The nomenclature of rota- viruses of human and animal origin, which do not possess the subgroup antigen common to the rota- viruses described above, remains to be resolved. Formal approval of this nomenclature will rest upon decisions made under the auspices of the Inter- national Committee for Taxonomy of Viruses. ACKNOWLEDGEMENTS We should like to thank the following for their reviews and comments: Dr J. Bridger, Compton, Berks, England; Dr S. Chiba, Sapporo, Japan; Dr R. Espejo, Mexico City, Mexico; Dr M. Estes, Houston, TX, USA; Dr I. Holmes, Melbourne, Australia; Dr R. Kono, Tokyo, Japan; Dr C. Mebus, Plum Island, NY, USA; Dr G. Woode, Ames, IA, USA; Dr R. Wyatt, Bethesda, MD, USA. REFERENCES 1. WOODE, G. N. ET AL. Morphological and antigenic relationships between viruses (rotaviruses) from acute gastroenteritis of children, calves, piglets, mice and foals. Infect. immun., 14: 804-810 (1976). 2. Zissis, G. & LAMBERT, J. P. Different serotypes of human rotaviruses. Lancet, 1: 39 (1978). 3. THOULESS, M. E. ET AL. Serotypes of human rota- viruses. Lancet, 1: 38-39 (1978). 4. YOLKEN, R. H. ET AL. Epidemiology of human rotavirus types I and 2 as studied by enzyme-linked immuno- sorbent assay. New Eng. j. med, 299: 1156-1161 (1978). 5. KAPIKIAN, A. Z. ET AL. Antigenic characterization of human and animal rotaviruses by immune adherence haemagglutination assay (IAHA). Infect. immun., 33: 415-425 (1981). 6. KALICA, A. R. ET AL. Genes of human (strain Wa) and bovine (strain UK) rotaviruses that code for neutraliz- ation and subgroup antigens. Virology, 112: 385-390 (1981). 7. GREENBERG, H. ET AL. Serological analysis of the sub- group protein of rotavirus using monoclonal anti- bodies. Infect. immun., 39: 91-99 (1983). 8. BASTARDO, J. W. ET AL. Preparation and characteriz- ation of antisera to electrophoretically purified SAl 1 virus polypeptides. Infect. immun., 34: 641-647 (1981). 9. KILLEN, H. M. & DIMMOCK, N. J. Identification of a neutralization-specific antigen of a calf rotavirus. J. gen. virol., 62: 297-311 (1982). 10. DYALL-SMITH, M. L. ET AL. Gene mapping of rotavirus double-stranded RNA segments by Northern blot hybridization: application to segments 7, 8 and 9. J. virol., 46: 3 17-320 (1983). 11. MASON, B. B. ET AL. Biochemical mapping of the Simian rotavirus SA 11 genome. J. virol., 46: 413-423 (1983). NOMENCLATURE OF HUMAN ROTAVIRUSES 503 12. WYATT, R. G. ET AL. Definition of human rotavirus serotypes by plaque reduction assay. Infect. immun., 37: 110-115 (1982). 13. BEARDS, G. M. ET AL. Rotavirus serotypes by serum neutralisation. J. med. virol., 5: 231-237 (1980). 14. SATO, K. ET AL. Antigenic relationships between rota- viruses from different species as studied by neutraliz- ation and immunofluorescence. Arch. virol., 73: 45-50 (1982). 15. URASAWA, S. ET AL. Three human rotavirus serotypes demonstrated by plaque neutralization of isolated strains. Infect. immun., 38: 781-784 (1982). 16. KUTSUZAWA, T. ET AL. Isolation of human rotavirus sub- groups 1 and 2 in cell culture. J. clin. rnicrobiol., 16: 727-730 (1982). 17. WYATT, R. G. ET AL. Direct isolation in cell cultures of human rotaviruses and their characterization into four serotypes. J. clin. microbiol., 18: 310-317 (1983). 18. HOSHINO, Y. ET AL. Serotypic similarity and diversity of human and animal rotaviruses as studied by plaque reduction neutralisation. J. inf. dis. (in press). Bulletin de l'Organisation mondiale de la Sante, 62 (3): 505-507 (1984) © Organisation mondiale de la Sante 1984 Nomenclature des rotavirus humains: designation des sous-groupes et des serotypes* Une nouvelle nomenclature est proposee pour les rotavirus humains sur la base de la spdcificitd des antigenes de sous-groupe et de se'rotype, respectivement situes sur le polypeptide principal de la capside interne et sur celui de la capside externe. Les sous- groupes sont de'signes par un chiffre romain (I et II) et les serotypes par un chiffre arabe (1, 2, 3, 4). Peu apres la decouverte des rotavirus humains, on a montre que ceux qui etaient alors connus avaient en commun un antigene de <<groupe>>, situe dans la couche capsidique interne (1). L'existence de diffe- rents <serotypes>> a par ailleurs e signalee pour la premiere fois A Bruxelles (Belgique) et a Birmingham (Angleterre), er 1978 (2, 3). La distinction etait etablie a Bruxelles par une epreuve de fixation du complement et par immuno-microscopie electro- nique avant de 1'etre A Bruxelles comme A Bethesda (Etats-Unis d'Amerique) par une technique immuno- enzymatique en phase heterogene (ELISA) (2, 4). A Birmingham, la distinction etait etablie par une epreuve de neutralisation des foyers d'immuno- fluorescence (NFIF) permettant de mesurer la capa- cite des serums a neutraliser l'infection de cellules en culture par des virus isoles de selles humaines. On admettait alors que toutes les epreuves met- taient en evidence des specificites identiques ou ana- logues; on a donc employe le terme de <<s6rotype>> pour caracteriser les entites ainsi definies. Mais par la suite on s'est aperqu que certains virus animaux, comme le virus de la diarrhee du veau du Nebraska et le virus 0, donnaient les memes reactions que les membres du <<s6rotype 1>> des rotavirus humains (5). Cette observation ne laissait pas d'etre etonnante puisqu'on sait que les rotavirus animaux ont, par rapport aux rotavirus humains, des specificites diffe- rentes en matiere de neutralisation (1). Cette ano- * La presente note de terminologie a ete redige par le Comite d'orientation du Groupe scientifique de travail pour les diarrhees d'origine virale du Programme OMS de lutte contre les maladies diarrheiques. Ce Comite est constitue des sp&ialistes suivants: P. A. Bachmann, Institut de Microbiologie medicale, Universite de Munich, Munich, Republique federale d'Allemagne; R. F. Bishop, Department of Gastroenterology, Royal Children's Hospital, Park- ville, Victoria, Australie; T. H. Flewett, Regional Virus Labora- tory, East Birmingham Hospital, Birmingham, Angleterre; A. Z. Kapikian, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, Etats-Unis d'Amerique; M. M. Mathan, Christian Medical College Hospital, Vellore, Tamil Nadu, Inde; et 0. Zissis, Departement de Virologie medicale, Hopital Saint-Pierre, Bruxelles, Belgique. La version originale en anglais est publiee aux pages 501-503. Les demandes de tire a part doivent etre adressees au Programme de lutte contre les maladies diarrheiques, Organisation mondiale de la Sante, 1211 Geneve 27, Suisse. malie apparente a et expliquee lorsqu'on s'est apercu que la designation originale de <<s6rotype>> (2) ne se confondait pas avec la specificite de neutrali- sation (5). Finalement, l'etude de virus recombinants a montre que ces deux specificites etaient codees par des genes differents (6). On a alors propose d'utiliser le terme de sous-groupe pour designer la specificite codee par le 6' gene et celui de s&rotype pour designer la specificite de neutralisation codee par le 9g gene (virus Wa) (5, 6). LOCALISATION DES ANTIGtNES DE SOUS-GROUPE ET DES ANTIGtNES DE StROTYPE On sait maintenant que les antigenes de sous- groupe sont situes dans le polypeptide principal de la capside interne, de masse moleculaire relative egale a environ 46 000. Ce polypeptide est un produit du 6' segment genomique et l'on a actuellement mis en evi- dence par immuno-enzymologie ou par une epreuve d'hemagglutination par immunoadherence deux antigenes de sous-groupe, serologiquement distincts. Les anticorps diriges contre ces polypeptides de sous- groupe n'ont qu'un pouvoir neutralisant faible, sinon nul (8, 9). On a prepare des anticorps mono- clonaux specifiques de chacun de ces deux antigenes (7). De leur cote, les antigenes de serotype se situent dans le polypeptide principal de la capside externe. II s'agit d'un polypeptide glycosyle, de masse molecu- laire relative egale a environ 36 000. La neutrali- sation est principalement le fait des anticorps diriges contre ce polypeptide; dans la plupart des souches, c'est un produit du 9' segment genomique. Cepen- dant, chez certaines souches, le segment codant peut occuper la 7' ou la 8' position, comme le montre l'electrophorese en gel de polyacrylamide (10, 11). Normalement, les serotypes sont identifies au moyen d'une epreuve de neutralisation revelee par reduction des plages ou des foyers d'immunofluorescence (12, 13). Les criteres retenus pour l'identification de nou- 4425 -505 506 NOMENCLATURE DES ROTAVIRUS HUMAINS veaux serotypes dependent de l'epreuve choisie et des serums utilises. Un virus est considere contre appar- tenant a nouveau serotype quand, par l'epreuve de reduction des plages pratiquee avec des serums hyperimmuns, la difference de titre entre les reac- tions homologue et heterologue atteint 20 fois (12). Mais si l'on se sert de serum de convalescent pour l'epreuve de reduction des plages ou si l'on fait appel a l'epreuve de reduction des foyers d'immunofluo- rescence (12, 13), la difference peut ne pas depasser 8 fois. NOMENCLATURE PROPOStE Pour eviter toute confusion dans les publications et pour respecter les priorites, il est propose d'ap- pliquer aux souches de rotavirus humains la nomen- clature suivante: 1. Les sous-groupes de rotavirus seront designes par des chiffres romains, a savoir I et II. 2. Les s&rotypes de rotavirus seront designes par des chiffres arabes, a savoir 1, 2, 3, 4. Selon ce systeme, les rotavirus humains peuvent etre designes comme suit: Souches reprdsentatives de rotavirus humains Sous-groupe S&rotype (12, 14-17) DS-1, S2, KUN I 2 Wa, K8, KU II 1 M, P, ITO, NEMOTO, YO II 3 ST4, HOCHI, HOSOKAWA II 4 Certain rotavirus animaux peuvent etre rattaches au meme systeme: c'est ainsi que le virus SA-11 reagit comme le serotype 3, sous-groupe I et que le virus de la diarrhee du veau du Nebraska reagit comme le sous-groupe I tandis qu'il se distingue par son serotype des quatre rotavirus humains (18). La numerotation des nouveaux serotypes se fera dans l'ordre pour les rotavirus humains (ou ani- maux) partageant avec l'un des virus decrits ci-dessus l'antigene de groupe. Reste a resoudre le probleme de la nomenclature des virus d'origine humaine ou animale qui ne possedent pas I'antigene de sous- groupe commun a tous les rotavirus decrits ci-dessus. L'adoption officielle de la nomenclature ainsi pro- posee reste subordonnee a la decision du Comite International de Taxonomie des Virus. REMERCIEMENTS Les auteurs tiennent a remercier les personnalites suivantes qui ont bien voulu examiner le projet du present article et leur faire part de leurs observations: D' J. Bridger, Compton, Berks., Angleterre; D' S. Chiba, Sapporo, Japon; D' R. Espejo, Mexico, Mexique; D' M. Estes, Houston, TX, Etats-Unis d'Amerique; Dr I. Holmes, Melbourne, Australie; Dr R. Kono, Tokyo, Japon; Dr C. Mebus, Plum Island, NY, Etats-Unis d'Amerique; Dr G. Woode, Ames, IA, Etats-Unis d'Amerique; Dr R. Wyatt, Bethesda, MD, Etats-Unis d'Amerique. BIBLIOGRAPHIE 1. WOODE, G. N. ET AL. Morphological and antigenic relationships between viruses (rotaviruses) from acute gastroenteritis of children, calves, piglets, mice and foals. Infect. immun., 14: 804-810 (1976). 2. Zissis, G. & LAMBERT, J. P. Different serotypes of human rotaviruses. Lancet, 1: 39 (1978). 3. THOULESS, M. E. ET AL. Serotypes of human rota- viruses. Lancet, 1: 38-39 (1978). 4. YOLKEN, R. H. ET AL. Epidemiology of human rotavirus types I and 2 as studied by enzyme-linked immuno- sorbent assay. New Eng. j. med, 299: 1156-1161 (1978). 5. KAPIKIAN, A. Z. ET AL. Antigenic characterization of human and animal rotaviruses by immune adherence haemagglutination assay (IAHA). Infect. immun., 33: 415-425 (1981). 6. KALICA, A. R. ET AL. Genes of human (strain Wa) and bovine (strain UK) rotaviruses that code for neutraliz- ation and subgroup antigens. Virology, 112: 385-390 (1981). 7. GREENBERG, H. ET AL. Serological analysis of the sub- group protein of rotavirus using monoclonal anti- bodies. Infect. immun., 39: 91-99 (1983). 8. BASTARDO, J. W. ET AL. Preparation and characteriz- ation of antisera to electrophoretically purified SAl 1 virus polypeptides. Infect. immun., 34: 641-647 (1981). 9. KILLEN, H. M. & DIMMOCK, N. J. Identification of a neutralization-specific antigen of a calf rotavirus. J. gen. virol., 62: 297-311 (1982). 10. DYALL-SMITH, M. L. ET AL. Gene mapping of rotavirus double-stranded RNA segments by Northern blot hybridization: application to segments 7, 8 and 9. J. virol., 46: 317-320 (1983). 11. MASON, B. B. ET AL. Biochemical mapping of the Simian rotavirus SA 11 genome. J. virol., 46: 413-423 (1983). NOMENCLATURE DES ROTAVIRUS HUMAINS 507 12. WYATT, R. G. ET AL. Definition of human rotavirus serotypes by plaque reduction assay. Infect. immun., 37: 110-115 (1982). 13. BEARDS, G. M. ET AL. Rotavirus serotypes by serum neutralisation. J. med. virol., 5: 231-237 (1980). 14. SATO, K. ET AL. Antigenic relationships between rota- viruses from different species as studied by neutraliz- ation and immunofluorescence. Arch. virol., 73: 45-50 (1982). 15. URASAWA, S. ET AL. Three human rotavirus serotypes demonstrated by plaque neutralization of isolated strains. Infect. immun., 38: 781-784 (1982). 16. KUTSUZAWA, T. ET AL. Isolation of human rotavirus sub- groups 1 and 2 in cell culture. J. clin. microbiol., 16: 727-730 (1982). 17. WYATT, R. G. ET AL. Direct isolation in cell cultures of human rotaviruses and their characterization into four serotypes. J. clin. microbiol., 18: 310-317 (1983). 18. HOSHINO, Y. ET AL. Serotypic similarity and diversity of human and animal rotaviruses as studied by plaque reduction neutralisation. J. inf. dis. (sous presse).