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Showing posts with label phylogeny. Show all posts
Showing posts with label phylogeny. Show all posts

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), 4760-4799
Click on image to enlarge.
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:

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

    Updated MERS-CoV full genome tree...

    With thanks to @arambaut for some tips, and for tying my home computer up for 2-days running PHYML on the sequences (super-computer it ain't) - this is a slightly more robust tree of the MERS-CoV complete (or near-complete) genome nucleotide sequences published to date. This follows from my previous post and tree here.

    Very little from 2014 despite the majority of MERS-CoV variants circulating then. But of course we have to wait because next generation sequencing is the main way we roll with MERS-CoV.

    Alignment of 56 complete or near complete MERS-CoV genomes and an Egyptian divergent variant from a camel. Alignment made using Geneious v6.1.7. The PHYML v2.2.0 plug-in was added to make this tree, using 1000 bootstraps. Red stars indicate 
    virus which is reportedly from the same patient (seems doubtful). Vertical bars to the right indicate Clade A (dark blue) and B (pale blue). Sequences from the the 2013 Al-Ahsa hospital outbreak are boxed in pink; from the Jeddah 2014 hospital outbreak in blue; from  the Hafr Al-Batin community cluster in green. Camel icons indicate genomes from camel variants for MERS-CoV. GenBank accession numbers are indicated at the end of each sequence name which also includes region of detection, host (human if not specified) and year of sample collection.
    Click on image to enlarge.

    The tree really highlights how remarkably interwoven the camel and human MERS-CoV genome sequences are; remembering that these 30,000nt genomes don't differ from each other by more than 1% at the nucleotide level.

    Some new sequence analyses from the Netherlands cases should be coming out in the next issue of Eurosurveillance so get a tab ready and keep hitting refresh. Or, ya know, go get a life or something (I'm hitting refresh).

    T.perforatus MERS-CoV strain sequence, and others, online...

    If you're a bit of a sequence collector/hoarder/nut then you'll be interested to know that the recent bat CoV RNA-dependent RNA polymerase (RdRp) sequences are now online on GenBank.

    These seem to include the primer regions judging by their length. Consider that when using them.

    The MERS-CoV strain from T.perfortaus is CII_KSA_287 - highlighted in bold. Please note, that at writing, it is erroneously identified on GenBank as originating from Rhinopoma hardwickii. It should be Taphozous perforatus.

    Understanding phylogeny....how virus sequence relate to each other through time

    Over at Edinburgh University, there is an awesome Molecular evolution, phylogeneticis and epidemiology's website. 

    On it's "epidemic" blog, run by Prof. Andrew Rambaut, there is a fantastic new primer on how to read a phylogenetic tree.


    I highly recommend this for all levels of skill. It provides a great and colourful background to what a phylogenetic tree does, and does not, convey. 


    Of particular interest, an example includes bat and camel virus sequences. Also relevant to interpreting future MERS-CoV trees as part of the infection source/animal host debate.


    These trees were drawn in FigTree (Mac and Windows versions avail,able) and polished using Adobe Illustrator.

    Coronavirus family tree....

    The phylogenetic tree below shows the relationships among the four genera of coronaviruses (CoVs); Genus Alphacoronavirus, Betacoronavirus, Deltacoronavirus, Gammacoronavirus

    This tree is based on full length genomes (nucleotides; aligned using Geneious Pro; Neighbor-Joining tree built using Mega with 500 bootstraps). 

    The MERS-CoV clade of betacoronaviruses is marked on the left and the endemic human CoVs are indicated with yellow triangles.


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