VirusBank

import { encodeTool } from '/_js/functions.js'

FA = FileAttachment

// Load the toolbox
families = await FA("/families.json").json()
_toolbox = await FileAttachment("/toolbox/toolbox.json").json()
toolbox = _toolbox.map( tool => encodeTool(tool) )

// console.log(toolbox)

addEncodedTools = (virus) => {
  return ({ ... virus, tools: toolbox.flatMap( tool => virus[tool.encoded] ? tool.id : []) }) 
}

// Load all Newick tree file and create a dictionary `family -> tree`
nwks = await Promise.all(
  families.map(async (family) => { 
    let tree = await FA("/"+ family + "/tree.newick").text()
    return ({ family: family, nwk: tree })
  }))
nwksAsMap = Object.fromEntries(nwks.map( el => [el.family, el.nwk] ))

// console.log(nwks)

// Load annotations for viruses for each family
_annotations = await Promise.all(
  families.map( async (family) => {
    let xls = await FA("/"+ family + "/family.xlsx").xlsx()
    let _annotations = xls.sheet(0, { headers: true, range: ":L" })

    let _trimmed = _annotations.map( virus => {
      let trimmed = {}
      Object.keys(virus).forEach( key => {
        trimmed[key] = virus[key].trim()
      })
      return trimmed
    })

    return _trimmed.map( virus => ({... virus, family: family }) )
  }))

// console.log(_annotations)

// Add tools information, just the list of tools ids
annotations = _annotations
  .flat()
  .map( virus => addEncodedTools(virus) )

familyAnnotations = annotations
  .filter(virus => virus.family == virusFamily)

function virusInfo(_family, _virus) {
  const info = 
    familyAnnotations.filter(row => row.abbreviation == _virus && row.family == _family)
  return info[0]
}

// Handle grouped viruses by extending the model with isGroup: false/true
addGrouped = (virus) => {
  const isGroup = (typeof virus.group_abbreviation !== "undefined") && (virus.group_abbreviation !== "")
  const virus_pointer = (isGroup) ? virus.group_abbreviation : virus.abbreviation 
  return (
    { ... virus,
      isGroup: isGroup,
      virusPointer: virus_pointer,
      resVirusId: (isGroup) ? virus.group_abbreviation : virus.abbreviation,
      resAbbreviation: (isGroup) ? virus.group_abbreviation : virus.abbreviation,
      resVirusName: (isGroup) ? virus.group_virus_name : virus.virus_name 
    }
  )
}

// Create a list of all viruses of interest in the Excel file
// Add group information early on
annotatedViruses =
  familyAnnotations
    .filter(virus => virus.virus_of_interest == "Yes")
    .map(virus => addGrouped(virus))

// Create a sublist of viruses with toolbox
// Take into account groups by selecting unique entries
toolboxAnnotatedViruses =
  annotatedViruses
    .filter(virus => virus.availability_in_toolbox == "Yes")
    .filter((value, index, self) => {
      return self.findIndex(v => v.resAbbreviation === value.resAbbreviation) === index;
    })

// Derive a virus object from the ID
// The ID can be either a virus_id (from the ictv tree) or a group_abbreviation
virusIdToVirus = (virus_id) => {

  // lookup the virus_id in the full list of viruses
  const fullList =
    annotatedViruses
      .filter(v => v.virus_id.replace(/^'+|'+$/g, '') == virus_id || v.abbreviation == virus_id)
      //.filter(v => v.virus_id == virus_id || v.abbreviation == virus_id)

  // lookup the abbreviation for the group
  const groupList =
    toolboxAnnotatedViruses
      .filter(v => v.group_abbreviation == virus_id)

  if (fullList.length > 0) {
    return fullList[0]
  }
  if (groupList.length > 0) {
    return groupList[0]
  }
}

// Return all matches for a virus ID
virusIdToViruses = (virus_id) => {
  // lookup the virus_id in the full list of viruses
  const single_virus =
    annotatedViruses
      .filter(v => v.virus_id.replace(/^'+|'+$/g, '') == virus_id || v.abbreviation == virus_id)
      [0]

  if (single_virus.isGroup) {
    return annotatedViruses
      .filter(v => v.group_abbreviation == single_virus.group_abbreviation)
  } else {
    return [ single_virus ]
  }
}

function renderVirusToolbox(family, virus_id) {

  // First extract the virus object from the ID or abbreviation
  // This takes into account the groups
  const virus = virusIdToVirus(virus_id)

  if (typeof virus.tools !== "undefined" && virus.tools.length > 0) {
    return html`
      ${toolbox.filter(tool => virus.tools.includes(tool.id) ).map(tool => 
        html`
        <h2 id="${tool.id}-section">${tool.name}</h2>
        <div class="container grid">
          <div class="g-col-12 g-col-md-3 toolbox one-tool" style="text-align:center;">
            <div id="toolbox-contents" class="tool-container">
              <a href="/toolbox/index.html#${tool.id}-section">
                <div class="tool-wrapper">
                  <div id="${tool.id}" class="tool">
                    <div class="tool-tooltip-text">${tool.name}</div>
                    ${tool.icon.map( i =>
                    html`<img class="tool-icon" height="${(tool.icon.length > 1) ? 150/tool.icon.length : 100}%" src="${i}"/>`
                    )}
                  </div>
                </div>
              </a>
            </div>
          </div>
          <div class="g-col-12 g-col-md-9">
            <p>${tool.description}</p>
          </div>
          <div class="g-col-1" style="text-align:center;">
          </div>
        </div>
        <div class="col-xs-12" style="height:20px;"></div>
        `
      )}
    `
  }
   else {
    return html`
      <p>&nbsp;</p>
    `
   }
}

import { virusInfoOrUndefinedF } from "/_js/functions.js"
import { availableVirusInfoF } from "/_js/functions.js"
import { availableToolsF } from "/_js/functions.js"
import { virusOfInterestF } from "/_js/functions.js"

  import {virusInfoOrUndefinedF as virusInfoOrUndefinedF} from "/_js/functions.js"

  import {availableVirusInfoF as availableVirusInfoF} from "/_js/functions.js"

  import {availableToolsF as availableToolsF} from "/_js/functions.js"

  import {virusOfInterestF as virusOfInterestF} from "/_js/functions.js"

// Initialize a container to contain the containers for the tree and annotation window
html`

<!-- Show information on hovered virus, reuse the same class for convenience -->
<div class="phylo-container">
  <!-- Left part -->
  <div class="left">
    <div id="info-container" class="text-center" style="visibility:hidden;">
        <div id="name" class="g-col-md-12 bold">
          name
        </div>
        <div id="toolbox" class="g-col-md-12">
          no tools yet for this virus
        </div>
    </div>
  </div>
  <!-- Right part -->
  <div id="annotation-container" class="right no-gutter">
    <p>&nbsp;</p>
  </div>
</div>

<div class="phylo-container">

  <!-- Left part -->
  <div class="left">
    <div id="tree-container" class="tree-container">
      <svg id="tree-svg" class="tree-svg"></svg>
    </div>
    <div id="legend-container" class="text-center mb-2">
      <div class="grid">
        <div class="g-col-md-12 small">
          <span class="phylotree-node-text" style="font-size:15px !important;">HOVER</span> for more information /
          <span class="phylotree-node-text-hl" style="font-size:15px !important;">BOLD NODES</span> are present in collection and can be selected 
        </div>
      </div>
    </div>
  </div>

  <!-- Right part -->
  <div id="annotation-container" class="right no-gutter">
    <div class="container grid small" align="center" style="--bs-gap: 1.0rem;font-weight:500;">
      <div class="g-col-md-12 g-col-sm-12 card card-body tool-header opacity-100" id="virus">
        Viral Toolbox
      </div>
    </div>
    <div class="container">
      <div class="toolbox">
          <div id="toolbox-contents" class="tool-container">
          </div>
      </div>
    </div>
  </div>

</div>
`

name

no tools yet for this virus

HOVER for more information / BOLD NODES are present in collection and can be selected

Viral Toolbox

phylotree = await require("phylotree@1.1/dist/phylotree.js");

phylotree = Object {centerOfTree: ƒ(tree, power), clusterPicker: ƒ(tree, bootstrap_threshold, diameter_threshold, root_node, missing_bootstrap_value), computeMidpoint: ƒ(tree), extract_dates: ƒ(…), fitRootToTip: ƒ(tree), getDistanceMatrix: ƒ(seqs), inOrder: ƒ(node, callback, backtrack), leftChildRightSibling: ƒ(root), loadAnnotations: ƒ(tree, label, annotations), neighborJoining: ƒ(distanceMatrixArr, n, nodeList), pairwise_distances: ƒ(tree), parseAnnotations: ƒ(buf), parseFasta: ƒ(fastaData), phylopart: ƒ(tree, bootstrap_threshold, percentile_threshold, missing_bootstrap_value, resolution), phylotree: class, postOrder: ƒ(node, callback, backtrack), preOrder: ƒ(node, callback, backtrack), rootToTip: ƒ(tree), sackin: ƒ(tree)}

virusInfoOrUndefined = virusInfoOrUndefinedF(familyAnnotations)
availableVirusInfo = availableVirusInfoF(familyAnnotations)
availableTools = availableToolsF(familyAnnotations, toolbox)
virusOfInterest = virusOfInterestF(familyAnnotations)

// Initialize the toolbox when the data is loaded
init_toolbox =
  toolbox.map(tool =>
    d3.select("#toolbox-contents").node().append(
      html`
        <a href=${get_link("toolbox", "#" + tool.id + "-section")} target="_top">
          <div class="tool-wrapper">
            <div id="${tool.id}" class="tool">
              <div class="tool-tooltip-text">${tool.name}</div>
              ${tool.icon.map( i =>
              html`<img class="tool-icon" height="${(tool.icon.length > 1) ? 150/tool.icon.length : 100}%" src="${i}"/>`
              )}
            </div>
          </div>
        </a>
      `
    )
  )

// Reset the tools in the Toolbox
clearToolbox = () => {

  d3.select("#virus").text("Viral Toolbox")

  toolbox.map(tool => {
    d3.select("#" + tool.id).attr("class", "tool")
  })
}

// Update the tools in the toolbox based on the provided virus object
updateToolbox = (virus) => {

  d3.select("#virus").text(virus.resVirusName)
  toolbox
    .filter(tool => virus.tools.includes(tool.id))
    .map(tool =>
      d3.select("#" + tool.id).attr("class", "tool tool-selected")
    )
}

// Handle tabset depending on the number of tabs
rawTabs = d3.select("#vb-tabset").select("ul").selectAll("li").select("a").nodes()
nrTabs = rawTabs.length

function indexToTab(i, length) {
  const pre = "tabset-" + (length + 1) + "-"
  const post = "-tab"
  return pre + (i+1) + post
}
 
tabsetAnchor = indexToTab(0, nrTabs)

virusIdToTabMap = new Map(
  toolboxAnnotatedViruses
    .map( (virus,i) => [ virus.resAbbreviation, indexToTab(i, nrTabs) ] )
)

tabToVirusIdMap = new Map(
  Array.from(virusIdToTabMap, a => a.reverse())
)

// Hide virus information tabset
function hideTabset() {
  const virusInfo = document.getElementById(tabsetAnchor).parentNode.parentNode.parentNode
  virusInfo.style.display = "none"
}

hide = hideTabset()

// Instantiate tree
nwk = nwksAsMap[virusFamily]
tree = new phylotree.phylotree(nwk)   // class Phylotree
                                      // https://github.com/veg/phylotree.js/blob/master/src/main.js#L90

// import { update_tree } from "/_js/functions.js"

renderedTree = tree
  // Transform the tree (translate and prune)
  // based on the input Excel file for this virus family
  .traverse_and_compute(node => {

    const virus_id = node.data.name
    const isLeaf = tree.isLeafNode(node)

    if (isLeaf) {
      const virus = virusIdToVirus(virus_id)
      const isVirusOfInterest = (typeof virus !== "undefined") ? (virus.virus_of_interest == "Yes") : false
      if (isVirusOfInterest) {
        const currentName = virus_id
        const newName = virus.abbreviation.trim()
        node.data.name = newName
      } else {
        node.data.name = "remove_me"
        tree.deleteANode(node)
      }
    } 
  })
  .render({
    'width': 600,
    'height': 600,
    'left-right-spacing':  'fit-to-size',
    'top-bottom-spacing':  'fit-to-size',
    'is-radial':          true,
    'selectable':         false,
    'collapsible':        false,
    'transitions' :       false,
    'show-menu':          false,
    'show-scale':         false,
    'align-tips':         true,
    'zoom':               false,
    'brush':              false,
    'draw-size-bubbles':  false,
    'maximum-per-node-spacing': 500,
    'minimum-per-node-spacing': 100,
    'maximum-per-level-spacing': 500,
    'minimum-per-level-spacing': 100,
    'container': "#tree-container"
  })
  .style_nodes( (element, data) => {
    // the virus_id is how the virus is encoded in phylotree newick file
    const virus_id = data.data.name  
    
    // At this stage in the process, every node should have information
    const information = virusIdToVirus(virus_id) // virusInfoOrUndefined(virus_id)

    const inToolbox = (typeof information !== "undefined") && (information.availability_in_toolbox == "Yes")

    // Styling based on available information
    const updtElement1 =
      information 
        ? element.select("text").attr("class", "phylotree-node-text")
        : element.select("text").attr("class", "phylotree-node-text-inactive")
    const updtElement = inToolbox ? element.select("text").attr("class", "phylotree-node-text-hl") : element

    // Hover functionality - Virus name
    if (information)
      element
        .on("mouseover", virusHoverIn(data, information, inToolbox))
        .on("mouseout", virusHoverOut)
 
    // Click functionality - Toolbox
    inToolbox
      ? element.on('click', function(el) {
          clearToolbox();
          // Select the first tab in order to get to the root of the tabset
          const virusInfo = document.getElementById(tabsetAnchor).parentNode.parentNode.parentNode
          virusInfo.style.display = "block"
          virusInfo.scrollIntoView(true)
          // Now get the proper tab and open it
          const thisVirusInfo = document.getElementById(virusIdToTabMap.get(information.virusPointer))  // either the virus_id or the group abbreviation
          thisVirusInfo.click();

          // Experiments
          clearNodes()
          highlightNodes(virus_id)

          // Render the toolbox for this virus
          updateToolbox(information);
        })
      : element.on('click', function() {
          hideTabset()
          clearToolbox()
        })

  })
  .layout(true)

// Based on a virus ID (abbreviation), highlight the virus or the whole group it belongs to
highlightNodes = (virus_id) => {
  const abbreviations = virusIdToViruses(virus_id).map(v => v.abbreviation)

  d3.selectAll("g")
    .filter(function (d) { return (typeof d.data !== "undefined") ? abbreviations.includes(d.data.name) : false})
    .select("text").attr("class", "phylotree-node-text-selected")

}

// Initialize all viruses in the tree
clearNodes = () => {
  const inLst = annotatedViruses.map(v => v.abbreviation)
  const inToolboxLst = annotatedViruses.filter(v => v.availability_in_toolbox == "Yes").map(v => v.abbreviation)

  // Initialize all text
  d3.selectAll("g")
    .filter(function (d) { return (typeof d.data !== "undefined") })
    .select("text").attr("class", "phylotree-node-text")

  // Update toolbox entries
  d3.selectAll("g")
    .filter(function (d) { return (typeof d.data !== "undefined") ? inToolboxLst.includes(d.data.name) : false})
    .select("text").attr("class", "phylotree-node-text-hl")
}

// console.log(renderedTree)

showTree = renderedTree
  .svg
  .node()

// Show small virus information box on hover
virusHoverIn = (data, information, is_available) => () => {
  // First, populate the content
  const virusNameToShow =
    (information.resVirusName)
      ? information.resVirusName
      : (typeof information.virus_name !== "undefined")
        ? information.virus_name
        : ""
  d3.select("#name").text(virusNameToShow)
  if (information.tools.length > 0)
    d3.select("#toolbox").text("Viral tools are available, please select the virus for more information")
  else
     d3.select("#toolbox").text("No viral tools have been developed yet")
  // ... then show the content
  d3.select("#info-container").attr("style", "visibility:visible;")
}

virusHoverOut = () => {
  d3.select("#info-container").attr("style", "visibility:hidden;")
}

// Clicking on the tabs feeds the info back to the toolbox info
feedbackToolbox = d3.selectAll(".nav-item")
  .on('click', function(){
    const _id = d3.select(this).select("a").attr('id')
    const _virus_id = tabToVirusIdMap.get(_id)
    // We should only update the toolbox if an actual virus is selected
    // not if for instance the 'toolbox' tab is selected
    if (typeof _virus_id !== "undefined") {
      const _virus = virusIdToVirus(_virus_id)
      clearToolbox();
      updateToolbox(_virus)
      clearNodes()
      highlightNodes(_virus_id)
    }
  })
     
// Add SVG to the DOM
tmp = d3.select("#tree-container").node().appendChild(showTree)

// If the size of the SVG is smaller than the allocated 600px
// then resize it relatively to the fraction
// Allow for a bit of padding, hence the .95 factor.
newSizeF = (curSize) => {
    if (curSize < 600) {
      return 600 * (0.95 * 600 / curSize)
    } else {
        return curSize
    }
  }

newSize = newSizeF(renderedTree.size[0])
updateSize = renderedTree.set_size([newSize,newSize]).update()

virusInfoOrUndefined = ƒ(virus_id)

availableVirusInfo = ƒ(virus_id)

availableTools = ƒ(virus_id)

virusOfInterest = ƒ(virus_id)

init_toolbox = Array(6) [undefined, undefined, undefined, undefined, undefined, undefined]

clearToolbox = ƒ()

updateToolbox = ƒ(virus)

rawTabs = Array(2) [HTMLAnchorElement, HTMLAnchorElement]

nrTabs = 2

indexToTab = ƒ(i, length)

tabsetAnchor = "tabset-3-1-tab"

virusIdToTabMap = Map(2) {"EV-A71" => "tabset-3-1-tab", "EV-D68" => "tabset-3-2-tab"}

tabToVirusIdMap = Map(2) {"tabset-3-1-tab" => "EV-A71", "tabset-3-2-tab" => "EV-D68"}

hideTabset = ƒ()

hide = undefined

nwk = `((X02316:0.3252945029543982,GU219984:0.3445215742905273):0.0748826534338975,HRV:0.3347914067628908,((MZ171094:0.1656715162986374,((POL2LAN:0.12555882719160888,V01149:0.12282472919519088):0.004134255140666732,POL3L37:0.12456481459418028):0.04394048404142631):0.11158585149567968,(AY426531:0.32167849764464007,(((MF662690:0.13973831148986954,CAU05876:0.13459539879407595):0.02762466379235956,(AY421764:0.10413457376821139,AY421767:0.10898019034488632):0.05211088544526837):0.17672535662002303,(AF162711:0.14972458691036628,((OQ842446:0.11315331703428427,MN749143:0.12284423324794175):0.0307983483874279,((X80059:0.13135287255662464,X84981:0.12982253882304728):0.021904413924784538,(AY302558:0.1295458988413709,AY302539:0.14024755888376073):0.005691395657548726):0.005711205862142632):0.0020246125047686525):0.11806418394046059):0.028362832606513788):0.015797588352494785):0.12603378673526933);\r `

tree = Phylotree {newick_string: "((X02316:0.3252945029543982,GU219984:0.34452157429…88):0.015797588352494785):0.12603378673526933);\r\n", nodes: Zh, links: Array(35), parsed_tags: Array(0), partitions: Array(0), branch_length_accessor: ƒ(_node, new_length), branch_length: ƒ(_node, new_length), logger: console, selection_attribute_name: "selected"}

renderedTree = TreeRender {css_classes: Object, phylotree: Phylotree, container: "#tree-container", separation: ƒ(_node, _previous), _nodeLabel: ƒ(_node), svg: Pn, selectionCallback: null, scales: Array(2), size: Array(2), fixed_width: Array(2), font_size: 12, scale_bar_font_size: 12, offsets: Array(2), draw_branch: ƒ(), draw_scale_bar: null, edge_placer: ƒ(edge, where, radial_center), count_listener_handler: ƒ(), layout_listener_handler: ƒ(), node_styler: ƒ(element, data), edge_styler: null, …}

highlightNodes = ƒ(virus_id)

clearNodes = ƒ()

virusHoverIn = ƒ(data, information, is_available)

virusHoverOut = ƒ()

feedbackToolbox = Vn {_groups: Array(1), _parents: Array(1)}

tmp = SVGSVGElement {}

newSizeF = ƒ(curSize)

newSize = 673.3157713257275

updateSize = TreeRender {css_classes: Object, phylotree: Phylotree, container: "#tree-container", separation: ƒ(_node, _previous), _nodeLabel: ƒ(_node), svg: Pn, selectionCallback: null, scales: Array(2), size: Array(2), fixed_width: Array(2), font_size: 12, scale_bar_font_size: 12, offsets: Array(2), draw_branch: ƒ(), draw_scale_bar: null, edge_placer: ƒ(edge, where, radial_center), count_listener_handler: ƒ(), layout_listener_handler: ƒ(), node_styler: ƒ(element, data), edge_styler: null, …}

EV-A71
EV-D68

This virus appears to have evolved only recently with the first known strain isolated in 1965.

It was associated with an outbreak of neurological disease in the United States in 1969.

It then spread to Europe with outbreaks there in Bulgaria (1975) and Hungary (1978).

It has since spread to various countries in Asia (China, Japan, Taiwan, Cambodia and Vietnam) where it has been responsible for several very large epidemics.

renderVirusToolbox("enteroviruses", "EV-A71")

Cell-based assays

CPE reduction assay

This antiviral assay measures the ability of a tested compound to protect infected cells from virus-induced cytopathic effects (mostly virus-induced cell death). The cell viability can be determined in a colorimetric assay using MTS/PMS method.

Virus yield assay

This antiviral assay measures the ability of a tested compound to inhibit the viral replication in an infected cell culture through quantifying the viral RNA and the infectious virus loads released in the supernatant. This assay can be used for validation of compounds that show efficacy in CPE-reduction assays and to confirm that the compounds have direct effect on viral replication (not only cytoprotective).

Delay of treatment assay (Time-of-addition)

This a test to determine the stage(s) of the viral replication cycle at which the compound exerts its antiviral effect. Briefly, cells are treated with the compound at different time points prior or after the infection with the virus then cells are incubated for example until the end of one or 2 replication cycles. At the end of incubation, the intracellular and extracellular viral RNA loads at each time point are quantified by qRT-PCR to determine at which stage(s) the compound is still effective and when it loses its antiviral efficacy.

Plaque assay

This assay is a standard method to quantify infectious virus titers in a sample. Briefly, the test sample is serially diluted then aliquot of each dilution is added to a well in a cell culture plate with incubation to allow virus attachment followed by removal of the viral input and adding overlay of agarose or similar viscous material that limit the spread of viral infection. Under this condition, the attached virion will start to replicate producing more virions that will kill surrounding cells to generate a hole or plaque in the cell monolayer. By removal of the overlay and staining the live cells for e.g. by Crystal violet or methylene blue, this will provide a dark background for clear visualization of plaques. By counting the plaques at certain dilution(s), the plaque forming units (PFU)/mL can be calculated.

High-throughput screening

High throughput screening (HTS)

HTS is an approach in antiviral drug discovery involving the use of automated equipment to rapidly test huge libraries of chemical or biological materials with the aim of identifying hit molecules against specific viruses. HTS is usually done in culture plates with 384 or 1536 wells format using high performance liquid/plate handling devices.

Recombinant viruses

Reverse genetic system

A reverse genetic system is mostly a plasmid-based system that can be used to insert the desired mutations in the viral genome to study the effect of these mutations on viral replication, virulence, sensitivity to antiviral compounds in vitro and in vivo.

Reporter viruses

Reporter viruses are recombinant viruses engineered to carry reporter genes such as the one coding for fluorescent or luminescent proteins for development of high throughput antiviral assays or easily detection method for in vivo replication.

Animal infection models

Rodent models

Rodent models such as mice, rats and hamsters have been widely used to study viral infections. Such models allow to study host response and pathogenicity for wide variety of viruses. Moreover, these models are beneficial to assess the preclinical efficacy and safety of potential antivirals identified in cell culture assays.

Zebrafish models

Zebrafish (Danio rerio) are optically-transparent tropical freshwater fish of the family Cyprinidae that are widely used as vertebrate models of disease. They have remarkable genetic, physiologic and pharmacologic similarities to humans. Compared to rodents, the maintenance and husbandry costs are very low. Interestingly, zebrafish larvae have been shown to be susceptible to infection with some human viruses (herpes simplex virus type 1, influenza A virus, and chikungunya virus, human norovirus). Therefore, such a model can be used to study the pathogenesis as well as test antiviral drugs for specific human viruses in higher capacity and less cost compared to rodent models.

open virus page / reload family page

First described in 1962 in children hospitalized for pneumonia and bronchiolitis.

Since its discovery, during the long period of surveillance up to 2005, EV-D68 was reported only as a cause of sporadic outbreaks.

In August 2014, the United States and Canada experienced the first few cases of what resulted in the largest known EV-D68 outbreak in history. Unexpectedly, this outbreak of severe respiratory infections coincided with an upsurge in acute flaccid paralysis and cranial nerve dysfunction in children, which has caused concerns in the global community. Similar outbreaks were also seen in different European countries and Asian countries like Japan.

Subsequent EV-D68 epidemics were also seen in 2016 and 2018.

renderVirusToolbox("enteroviruses", "EV-D68")