Behind the naming of ebolaviruses... [UPDATE 2]

Just don't call me a taxi

Virus taxonomy is the classification of viruses into groups based on similarities. 

Today classification is supported by viral gene and genome sequence information.

The International Committee on Taxonomy of Viruses (ICTV) takes care of the official virus taxonomy. It has a pretty friendly website with a good search engine and the latest (2013 at writing) virus taxonomy can be found here. [1]

So what does it, and its tome, Virus Taxonomy, Ninth Report of the International Committee on Taxonomy of Viruses [2], have to say about ebolaviruses? Well, not as much as you might like, if you want to be able to name them, talk conversationally about them and discuss the issues around the disease resulting from infection by most of them. Sure, you can just call it all "Ebola" (which is a river in Africa by the way) and be done with it, but you'd be wrong. And some smart alec will correct you for sure. Here is where the ICTV Filoviridae Study Group fills in a lot of blanks.

One thing to get on top of first up. When talking or writing about these    looking little pathogens, we can just call lump them together under the conversational term "ebolaviruses" thus..."Hey Jeanette, did you hear about the latest ebolavirus infection numbers over the weekend?" is a question that could refer to any of the 5 very different viruses.

So, let's try and make that tearoom conversation a little more accurate.

The very dry detailed stuff down to the level of a species.

The italicization and the capitalization below are really important to taxonomy guys - so, ya know, care. 

Also, the ICTV reminds us that the name of the species is not the name of a virus - they are 2 different things. The species is a broad term for all the measurably different viruses out in the wild, that it contains. Here, species is to viruses what Mitsubishi Sigma is to identifying my old car. A virus name,

e.g. Ebola virus (see below), is like identifying my car as "a silver 1988 Mitsubishi Sigma". 

What if we used taxonomy on cars? A different way to explain how to name ebolaviruses.
Click to enlarge

The viruses we are talking about here belong to the order Mononegavirales, family Filoviridae, genus Ebolavirus. 

There are 5 species within the genus. The species names are in italics below. Underneath is the name of the virus (the virus belongs to the species container) and its abbreviation. The viruses in bold have caused outbreaks of human disease.

• Ta� Forest ebolavirus
• Ta� Forest virus (TAFV)
• Reston ebolavirus
• Reston virus (RESTV)
• Sudan ebolavirus
• Sudan virus (SUDV)
• Zaire ebolavirus
• Ebola virus (EBOV)
• Bundibugyo ebolavirus
• Bundibugyo virus (BDBV)

But what should I call the latest ebolavirus strain, variant, genotype, subtype, serotype, isolate thingy?

In the case of the current outbreak, that latest virus is an Ebola virus (EBOV), which we can now say belongs to the species Zaire ebolavirus (a Mitsubishi Sigma). 

But back to the car analogy. The silver 1989 Mitsubishi Sigma name is still not enough to tell it apart from any other silver Mitsubishi Sigma parked at the same shopping centre. How do you choose yours in a way that won't get you arrested for breaking into someone else's car? They both look like silver Mitsubishi Sigmas. But the silver Mitsubishi Sigma with license plate ABC 321 is yours and your alone, and that code differentiates your car from any other anywhere in the world.

We know from genome sequencing studies that the virus circulating in Guinea is an EBOV (a silver Mitsubishi Sigma) and is not identical to the one in (what was called) Zaire in 1976 (this silver Mitsubishi Sigma car has a different license plate). They couldn't be the same physical virus anyway, because each person hosts millions and millions of virions, each cell has a varied population of viruses in it, and each virion has a relatively short life. 

There is no universal definition for classification of viruses below the level of a species. But there are lots of terms that are used - most are listed in the heading to this section. In filovirus-land, the Study Group has sought to impart some order upon the chaos [3]. 

A virus strain needs to have 1 or more observable, genetically stable and unique differences compared to other viruses in the same species. For instance, one might cause a disease that is different from the one we know. So apart from a different license plate, it might also have an Awesome Mix #1 CD in the tray. 

From Kuhn et al.[5]
Viruses  2014, 6(11), 4760-4799Click on image to enlarge.

A variant has some genetic sequence or other differences that may result in a slightly different observable change. The West African EBOV is a variant and not a strain of Zaire ebolavirus and was named after the Makona river (see figure) which makes contact with all three countries that have had widespread and intense transmission.[5] For example, these from Guinea and Sierra Leone:

• Ebola virus H.sapiens-wt/GIN/2014/Makona-Kissidougou-C15, complete genome
• Ebola virus H.sapiens-wt/GIN/2014/Makona-Gueckedou-C07, complete genome
• Ebola virus H.sapiens-wt/SLE/2014/Makona-EM104

A virus isolate is a virus sample resulting from growing or culturing it in cells or tissues. Variants can therefore be represented by isolates. These isolates can be identical or slightly different (your neighbour could order the exact same car as you did-but he would still have a different license plate and no bobble-heads and fluffy dice).

The naming schemes do go into further detail, but you can read that in [3].

The disease.

The disease caused by EBOV, SUDV, TAFV and BDBV is called Ebola virus disease (EVD). Frankly, that is a tough one to explain after all of the above. It reads as though we are talking about just 1 virus causing disease (EBOV). But not so. Viruses from 4 species cause EVD - EBOV, SUDV, TAFV and BDBV. Diseases are named by World Health Organization's International Classification of Diseases (ICD) site, (4) and the name of this disease goes back many years and has not been updated yet. The disease has been called Ebola haemorrhagic fever, but is not now. Ebola virus disease is, by itself, a proper noun - that is its name - so it always gets the capital 'E'. And to continue from the taxonomy above, EVD is caused by a virus that can be ascribed to a species. In West Africa right now, EVD is due to infection by an Ebola virus variant classified in the species  Zaire ebolavirus.

Navigating a tree in the ebolavirus jungle.

Lastly, I've cobbled together a tree of genomes from each of the 5 ebolavirus species. It may help. Or not.

A phylogenetic tree of some genome sequences of the 5 species of ebolavirus, each indicated with a specific coloured dot.

References...

1. ICTV Virus Taxonomy: 2013 Release
   http://www.ictvonline.org/virusTaxonomy.asp
2. Ebola virus disease World Helath Organization fact sheet
   http://www.who.int/mediacentre/factsheets/fs103/en/
3. Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae.Arch Virol (2013) 158:301�311.
   http://download.springer.com/static/pdf/619/art%253A10.1007%252Fs00705-012-1454-0.pdf?auth66=1408093824_af9d701ab93574066469a6f6745c11d7&ext=.pdf
4. International Classification of Diseases (ICD)
   http://www.who.int/classifications/icd/en/
5. Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014
   http://www.mdpi.com/1999-4915/6/11/4760

Updates...

1. 05AUG2015: Added comment about Ebola virus disease being a proper noun

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Where the Guinea ebolaviruses hang in the jungle of the genus Ebolavirus

The 3 complete genomes from the NEJM article are boxed in pink.
Viruses that belong to the species Zaire ebolavirus, are boxed in blue
(including the Gueckedou and Kissidougou isolates).
With my thanks to Dr Stephan Gunther for providing these 3
genome sequences for this tree. Alignments were made using Geneious v6.1.6.
Neighbor-joining tree with 500 bootstraps made using Mega 6.06.
GenBank accession numbers are shown for each entry. Two representatives of the genus Marburgvirus are also included at the bottom of the tree.
Click on image to enlarge.

References...

1. Emergence of Zaire Ebola Virus Disease in Guinea � Preliminary Report
   http://www.nejm.org/doi/pdf/10.1056/NEJMoa1404505

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Naming the new Zaire ebolavirus variants

The recent NEJM paper [1,2] on the Guinea Ebola outbreak listed 3 full genome sequences (detected from infected people using standard "Filioviridae-specific RT-PCR assays" and published "real-time RT-PCR assays targeting the glycoprotein (GP) or nucleoprotein (NP) gene".

My thanks to Dr Stephen Gunther for answering my email and giving permission to list these names. They should be on Genbank now he tells me (I have not found them as yet). We now know that these virus variants of the species Zaire ebolavirus are called:

• Ebola virus H.sapiens-wt/GIN/2014/Gueckedou-C05
  GenBank accession number: KJ660346, KJ660347 or KJ660348
• Ebola virus H.sapiens-wt/GIN/2014/Gueckedou-C07
  GenBank accession number: KJ660346, KJ660347 or KJ660348
• Ebola virus H.sapiens-wt/GIN/2014/Kissidougou-C15
  GenBank accession number: KJ660346, KJ660347 or KJ660348

See more one the way the Filioviridae Study Group prefers to name ebolaviruses in a recent post here.[2]

On the issue of whether these variants can still be detected using published diagnostic PCRs, the answer is yes they can (they were detected using them after all!). To look more closely at that, I aligned the 3 new full genomes and also the primer sequences for 2 diagnostic reverse-transcription real-time polymerase chain reaction (RT-rtPCR) assays mentioned in the NEJM article by Baize and colleagues [3,4]. They target the nucleoprotein (NP; [4]) region of the genome and the glycoprotein (GP; [3])

The two PCR assay regions targeting GP and NP PCR oligonucleotides
(primers and fluorogenic probes) primers. The yellow stars in the NP assay
highlight a 2 nucleotide mismatches between the forward primer or probe
(T in oligo, A in genome) and the 3 genomes. These shouldn't decrease
assay sensitivity too much at all.
Click on image to enlarge.

References...

1. Emergence of Zaire Ebola Virus Disease in Guinea � Preliminary Report
   http://www.nejm.org/doi/pdf/10.1056/NEJMoa1404505
2. http://newsmedicalnet.blogspot.com.au/2014/04/update-on-ebola-virus-disease-evd-case_17.html
3. Development and Evaluation of a Fluorogenic 5 ' Nuclease Assay To Detect and Differentiate between Ebola Virus Subtypes Zaire and Sudan | Gibb and colleagues | J Clin Microbiol. 2001 p4125-30
   http://jcm.asm.org/content/39/11/4125.full.pdf+html
4. Rapid detection of filoviruses by real-time TaqMan polymerase chain reaction assays.| Huang and colleagues | Virologica sinica 2012 p273-7
   http://www.ncbi.nlm.nih.gov/pubmed/23001480

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Media MER muttering more than murmurs.

Ouch. Anyway, before you finish typing or reading that coronavirus outbreak story make sure it doesn't use the names human betacoronavirus 2c EMC, human betacoronavirus 2c England-Qatar, human betacoronavirus 2C Jordan-N3, betacoronavirus England 1 or (especially the short-sighted) novel coronavirus (NCoV)-they are so, like, yesterday's name. 

Prof Raoul J. de Groot and a host of coronavirus (CoV) experts, comprising the CoV Study Group, have penned a scientific article that has just been accepted into the Journal of Virology. The name of the newest spiky little killer is officially Middle East respiratory syndrome coronavirus or MERS-CoV for short. New variants (the same virus detected in other people/animals) will be given a name using the influenza virus naming system:

Virus name host/country of virus detection/variant identifier/year detected e.g. MERS-CoV Hu/Jordan-N3/2012).

That's as official as it gets anyway so this is how we should label it from here on in.

We're also avoiding calling it a human CoV until we know how humans get the infections. Since the virus is similar to a bat version one of many question is whether the cases all got it directly from bats (unlikely) or from human contact with another, intermediate, host. This builds on the media reports noted on 07.05.13.

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It's an nHCoV, its an EMC...no...its MERS?

It was an unusual move that apparently required "a great deal of effort to find a name that all parties involved could agree on". Avian Flu Diary reports on a ScienceInsider article noting that the Coronavirus Study Group will propose an entirely new name for the latest human coronavirus type that seems to cause respiratory disease in humans and belongs to a new coronavirus species. 

Usually the International Committee on Taxonomy of Viruses (ICTV) doesn't fiddle around with naming below the level of species and the new human coronavirus type seems to be part of a group of viruses (including bat coronaviruses) that together will likely form a novel species. Do the bat viruses also cause respiratory syndrome in humans...or other animals? There is likely to be some (more) confusion caused by this name change, and it is very possible that the press will not strictly adhere to the new name any more than the old one (an argument that supports either side of the debate).

So far the virus has been called novel coronavirus (NCOV-a name that never should have stuck-what do we call the next one....more novel CoV?) and in the scientific, peer-reviewed literature, HCoV-EMC after the laboratory that characterized the virus (Erasmus Medical Center). Still, its only about 8 months since we learned of the first case subsequently attributed to this virus in Sept 2012 (the patient presented in June 2012). How big could the body of literature be on EMC at this point? Apparently its 23 papers strong according to PubMED.

The new name for the disease and the virus group will change to MERS-CoV (Middle East respiratory syndrome). It will next go before the ICTV for ratification.

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