Viruses coming to TaiBNET

1. Viruses coming to TaiBNET Viruses in 臺灣 : How can ICTVdB facilitate the construction of a virus database in TaiBNET? • Cornelia Büchen-Osmond • Australian National University • Columbia University ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

2. How did we learn about viruses • symptoms known since thousands of years • as devastating diseases • in humans (small pox, polio) • in animals (foot-and-mouth disease) • in plants • tulip color breaking (potyvirus) • grapevine chrome mosaic (comovirus) ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

3. How old are viruses? determination of true age of viruses • no fossils to determine • genome sequence mutation, pair-wise comparison • phylogenetic tree analysis • ~1% decade in potyviruses • molecular clock says old • potyvirus in Australia introduced ~ 60,000 years • dsDNA animal virusesmuch older ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

4. Virology began with plant pathology Mosaic disease in tobacco plants ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

5. 110 years of virology • In 1892 the Russian scientist Iwanowski recognized that an infectious agent passing through a filter with a pore size of less than 250 nm was responsible for the mosaic disease affecting tobacco plants. • Beijerinck was the first who associated the term virus with the filterable infectious agent in tobacco plants. • he proposed that a virus was a culturable contagium vivum fuidum which multiplied in close association with the host's metabolism and was distributed in phloem vessels together with plant nutrients • his theory was in stark contradiction to the prevailing germ theory based on the metabolic pattern of bacterial diseases • only in the mid 1930’s the true nature of viruses was revealed as nucleoproteins ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

6. 110 years of virology • The first filterable infectious agent isolated from animals was the Foot-and-mouth-disease virus reported by Loeffler and Frosch in 1898 • By the beginning of the twentieth century, the concept of viruses as agents of human disease was established when Reed and Carroll recognized Yellow fever virus (Panama Canal) • Bacterial viruses were discovered independently in 1915 by Twort and by d'Hérelle in 1917 who coined the term bacteriophage, meaning "bacteria eater," to describe the agent's bacteriocidal ability . ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

7. Discovery of the causative agent • The cause of smallpox was understood much later • 1886 “elementary bodies” visualized in LM • 1925 multiplication of poxvirus in cultured cells and chick embryo chorioallantoic membranes (Parker and Nye; Goodpasture) • 1935 purification and chemical composition of vaccinia virus (Smadel & Hoagland) • 1943 EM of negatively stained particles (Ruska, Siemens) • 1954 EM thin sections of virus-infected cells (Morgan) • 1967 RNA polymerase in infectious particles • 1974 structure of poxvirus genome • 1994 complete genome sequence of Variola virus ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

8. What is a virus • viruses are found in all forms of life • subcellular entities consisting of • protein capsids • may have a lipid envelope • nucleoprotein/genome • dsDNA, ssDNA, dsDNA-RT, dsRNA, ssRNA, ssRNA-RT • totally dependent on the host • for genome transcription and replication • for assembly, maturation and egression ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

9. Virus infection is host specific • they can only infect a specific host • one or more host families • species specific • they can have a high mutation rates • they can recombine • they can acquire genes from the host • they can transfer genes Although much reduced forms of life, viruses are master explorers of the evolutionary space and are perhaps even a driving force in evolution and speciation. ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

10. Classification of Organisms Traditional Taxonomy based on morphology (using the naked eye and handheld lens) currently attempting to use molecular data(resulting in unclear relationships) Virus Taxonomy based also on morphology (using EM, x-ray diffraction and crystal structure) currently mainly using genomic sequence data ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

11. Early Classification Systems • In 1927 the need for a system of virus nomenclature and classification was recognized • Initially the classification scheme was based on plant, animal, and bacterial viruses • The earliest efforts to classify within a host group were based on • common pathogenic properties (symptoms) • common organ tropisms (liver, leaves etc) • common ecological and transmission characteristics • Viruses causing hepatitis were simply lumped together as “the hepatitis viruses” • This approach is still retained in the International Code of Diseases in which all virus diseases causing hepatitis are still lumped together under one basic code ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

12. Taxonomic Virus Properties Since the founding of ICTV (1961) the taxonomic status of a virus has been defined by • Virion properties • morphology • genome, protein, carbohydrates and lipids • Genome organisation and replication • metabolic interaction between virus and host • sequence annotations • Biological properties • host range and vectors • cyto- and histopathology (disease expression) • transmission, epidemiology, geographic distribution ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

13. Taxonomy of emerging viruses • 2 virus families24 floating genera 16 plant virus groups • 38 virus families138 genera/groups • 1 order50 families164 genera • 3 orders56 families233 genera • 3 orders73 families287 genera • 5 orders84 families314 genera 1971 1st Report 1990 5th Report • 6th Report • 7th Report • 8th Report 2008 ICTVweb ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

14. Virus nomenclature The International Committee on Taxonomy of Viruses • rules on classification and nomenclature • does not accept Linnaean style binomial nomenclature(genus name followed by species name) • recognizes taxonomic levels of Order, Family, Subfamily, Genus and Species with standardized Latinized endings • includes host, symptom, and/or location in species names • italicizes only a species name ending with “virus” ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

15. Examples of virus species names species name: Tobacco mosaic virus Alt. name: Tobacco mosaic tobamovirus virus name: Tobacco mosaic virus species name: Cercopithecine herpesvirus 1 synonym: Herpesvirus simiae (early attempt for true binomial nomenclature) virus name: Cercopithecine herpesvirus 1 species name: Tomato yellow leaf curl Sardinia virus synonym: Tomato leaf curl virus-Sardinia synonym: Tomato leaf curl virus - Sardinia synonym: Tomato leaf curl virus - Spain synonym: Tomato leaf curl virus – Sardinia [Spain] ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

16. ICTV-online since 2007 • a new database maintained by ICTV • each year, after final approval by all ICTV members, the latest Master Species list will be published online by ICTV • links to the ICTVdB “ Index of Viruses” and virus descriptions ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

17. ICTV-online entry for White spot syndrome virus first reported in shrimp aquaculture from Taiwan in 1992. This entry is based on ICTVdB “Index of Viruses” and this year updated by ICTV ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

18. Index of Viruses in ICTVdB Family Names in Taxonomic (genomic) Order ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

19. ICTVdB uses a decimal code to uniquely identify each virus The decimal code • gives every virus in ICTVdB a unique “IP number” • indicates its taxonomic status and level • serves as a link within the whole database • serves as a surrogate accession number in ICTVdB on the web and as hyperlink from other databases e.g., NCBI and SWISS-PROT or taxonomic databases such as Species2000 and GBIF • records changing taxonomic decisions by ICTV expert Study Groups, but retains old codes to chart the history of virus taxonomy ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

20. The decimal code in ICTVdB The decimal code for White spot syndrome virus indicates its taxonomic context …virales Order 00. Nimaviridae 00.103. Family Subfamily ….virinae 00.103.0. Whispovirus Genus 00.025.0.01. White spot syndrome virus 00.103.0.01.001. Species 00.103.0.01.001.00. 003. Isolate WSSV-1-TW(1992) ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

21. ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

22. Virus descriptions in ICTVdB ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

23. Interoperability in ICTVdB • Interoperability is achieved in descriptions • via decimal code within ICTVdB • from other databases to ICTVdB • on species level and above via • NCBI TaxID to retrieve nucleotide sequences, genomes and PubMed references • below species level via • sequence accession numbers • specific accession codes to • Databases: CDC, VIPERdB, VIDEdB, DPV (CMI/AAB) • Catalogs: ATCC, DSMZ, d’Herelle • Publications: ProMed, journals ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

24. ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

25. ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

26. and ICTVdB lists are the accepted world standard for virus names ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

27. ICTVdB in DELTA Format • three basic flat files plus many directives • character list (> 3000 questions to describe a virus) • specification file (specifies types of characters and dependencies) • Items file (coded data of >4000 virus descriptions) • dependencies make characters applicable or inapplicable, depending on choice and correspond to tables in relational databases • character list can be translated into other languages, including Chinese • easy transport of data set from • one language to another • one database to another The new ICTVdB platform will be in a relational database format using MySQL ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

28. Regional data sets • virus descriptions on isolate level with links • to species/genus level descriptions • to fact sheets • to sequence data • to host databases • to distribution maps for virus, host, vector • to images of virus, host vector • to references ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

29. Viruses of Plants in Australia • DELTA formatted database • regional data on viruses • on hosts and agronomic impacts • introduction to Australia • distribution in Australia • extensive host lists • on the WWW since 1992 • links to generic descriptions ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

30. Before viruses are entered in TaiBNET we need to have: • prepare lists of viruses in Taiwan • in humans • in agriculture • in husbandry • in aquaculture • in nature • in all forms of life • obtain data from taxonomic hierarchy tree in ICTV or GBIF • prepare short descriptions of isolate data • customize links to ICTVdB and genomic databases ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

31. Current ICTVdB DELTA System The current system is based on the DELTA format (DEscription Language for TAxonomy). At its core, Delta is based on linear lists of information (flat files) which specify taxa and their defining characteristics. The Delta system has been engineered to uniquely suit the needs of the worldwide taxonomic community and is used for the classification of plants, animals, viruses, etc... Unfortunately, this taxonomic format and the associated software are no longer being developed. Updates to the Delta database require a highly trained curator with an in depth knowledge of the system. Publication of the database to the web is done using a mixture of specialized programs, scripts and hand editing. As a result the web-based ICTVdB is actually a set of static web pages which must be regenerated each time data are released. Interactive virus identification is currently through the Windows application Intkey. Intkey is the interactive taxonomic keying system that is shipped with Delta. It allows a user to identify an organism by successive pruning of taxa. As details are entered about the organism, the number of taxa matching the specified information is listed. This is a valuable tool but the lack of cross-platform compatibility (Windows only) is a major complaint. Isolate data, describing viruses found around the world, are submitted through EntVir, a MySQL database system feed by PHP-based forms which also must be regenerated each time the database is published. Isolate data ultimately ends up as an email that is imported into the Delta system manually. In the current system, all isolate review and database entry is handled through a single curator. ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

32. Proposed ICTVdB System The proposed replacement architecture utilizes a relational database (MySQL) where the flat files have been translated to their equivalents in a relational database schema. The relational database will capture the taxonomic hierarchy, descriptive data for taxa, and isolate descriptions. Users will interact with the MySQL database through a custom web application with the following functions: Browse - A taxonomic tree will be used to navigate through viral taxa. This will allow visual browsing of the taxonomic hierarchy. Viruses will also be indexed by name, host and genome organization. Query - A basic search will allow users to query the taxonomic hierarchy, virus names and other data. The stand-alone IntKey application will be replaced by an advanced search function with a flexible system of forms and search refinement. Data Entry - An improved data entry system will be used to keep the ICTVdB up to date and to make data entry as simple as possible. Until this system is fully functional, the current EntVir system will remain in place. ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

33. Proposed System The proposed replacement architecture utilizes a relational database (MySQL) where the flat files have been translated to their equivalents in a relational database schema. The relational database will capture the taxonomic hierarchy, descriptive data for taxa, and isolate descriptions. Users will interact with the MySQL database through a custom web application with the following functions: Browse - A taxonomic tree will be used to navigate through viral taxa. This will allow visual browsing of the taxonomic hierarchy. Viruses will also be indexed by name, host and genome organization. Query - A basic search will allow users to query the taxonomic hierarchy, virus names and other data. The stand-alone IntKey application will be replaced by an advanced search function with a flexible system of forms and search refinement. Data Entry - An improved data entry system will be used to keep the ICTVdB up to date and to make data entry as simple as possible. Until this system is fully functional, the current EntVir system will remain in place. ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses

34. The database will be populated with data from several sources: One time conversion of current Delta format flat files to the databaseAnnual taxonomy and nomenclature updates from the ICTV executive committee Virus annotations made by Curators Contributors submission of virus isolates An important feature of the revised system is the concept of decentralized data entry and review. Isolate submission will be reviewed by the Head Curator and/or other specialists with knowledge of particular viral families. These Curators will be given the ability to review Pending isolate submissions for correctness and approve them for transfer from a Pending status to Approved isolates for release in the next ICTVdB version. Curators will be volunteers and will have the ability to decline to review isolates, in a manner similar to the peer review system used by journals. Yearly updates to the taxonomy will be made using the Master Species List maintained by the ICTV. The Master Species List contains the current description of virus taxonomy down to the species level and is updated, as needed, by the ICTV executive committee (EC). Decentralization is expected to greatly improve the accuracy and speed of the ICTVdB update process. ICTVdB the Universal Virus Database of the International Committee on Taxonomy of Viruses