Viruses in ?? : How can ICTVdB facilitate the construction of a virus database in TaiBNET?

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Viruses coming to TaiBNET

• Viruses in ?? How can ICTVdB facilitate the
  construction of a virus database in TaiBNET?

Cornelia Büchen-Osmond Australian National
University Columbia University
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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)

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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

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Virology began with plant pathology
Mosaic disease in tobacco plants
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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 1930s the true nature of viruses
  was revealed as nucleoproteins

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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 .

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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

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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

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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.
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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

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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

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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

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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

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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

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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

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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

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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
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Index of Viruses in ICTVdB

• Family Names in Taxonomic (genomic) Order

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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

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The decimal code in ICTVdB
The decimal code for White spot syndrome virus
indicates its taxonomic context
virales
Order
00.
00.103.
Nimaviridae
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)
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Virus descriptions in ICTVdB
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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, dHerelle
• Publications ProMed, journals

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and ICTVdB lists are the accepted world standard
for virus names
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ICTVdB in DELTA Format

• three basic flat files plus many directives
• character list (gt 3000 questions to describe a
  virus)
• specification file (specifies types of characters
  and dependencies)
• Items file (coded data of gt4000 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
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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

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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

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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

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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.

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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.

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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.

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The database will be populated with data from
several sources

• One time conversion of current Delta
  format flat files to the database Annual
  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.