The origin of Schmallenberg Virus and the need for more surveillance.

Last week we finally got the answer to where Schmallenberg virus came from. At least genetically speaking that is (we still don't know from what geographical region it was nor whether it had been in Europe this whole time). But we do now have some clues.

It has come to light that this previously unheard-of microbe is a mixture of two previously known and closely related viruses: Sathuperi and Shamonda viruses. Writing in Archives of Virology earlier this month, a Japanese group (Yanase et al, from the Japanese National Institute of Animal Health) delved into the depths of bunyavirus genetics and uncovered Schmallenberg's closest cousins by sequencing a number of other viruses from Africa and Australiasia. Sadly this paper is not open access.

I wrote about Schmallenberg virus soon after it was discovered earlier this year. This was the virus that popped up in sheep and cows last summer then by the time the next Spring came we quickly realised it's aftermath: it had induced a number of malformations in their young - who at the time of infection were in the womb. These often times had fatal consequences. 



Back then we had no idea where this virus had come from as it's genome sequenced really looked like nothing we had seen previously. The original paper only used one small part of the viruses genome to trace it's ancestry due to the low amount of sequence data for these viruses. Although it bore a distant relation to known viruses there were some significant gaps in our knowledge of genomes from this group of viruses.

A bunyavirus (from ViralZone). Note the three segments of genome.

You see Schmallenberg is a Bunyavirus, a group of single-stranded, negative-sensed RNA virus. But the special thing about these guys is that they are segmented. Just like influenza is. And we all know what flu likes to do with it's segmented genome: it likes to reassort and swap bits and pieces of it's self around. A bit like virus sex. Well Bunyaviruses do this as well and it turns out so did the direct ancestor to Schmallenberg.

The three segmented genome. Schmallenberg had the S and L of Shamonda and the M or Sathepuri. (From Viralzone)

When the Japanese group compared the Schmallenberg genome to those of the other viruses that they had just sequenced, the true ancestry of this deadly virus emerged. It was strikingly clear that it's entire genome did not share the same genetic history. Two of it's three segments were very closely related to the Shamonda viruses while the last segment seemed to have a different story to tell: it was more closely related to another, distinct virus called Sathepuri virus.

All this indicates is that at some point in time, two different viruses (Shamonda and Sathepuri) infected the same cell - maybe in an insect, maybe in a mammal - out came a entirely, never-before-seen virus. This virus somehow made it's way to North-West Europe and started infecting various biting insects and farm animals. We can't yet say where this occurred, nor can we say when but what we can say is that it definitely happened. We also can't be sure of what genetic changes the virus had to make in order to function as this kind of chimera and for it to spread into a new geographic niche.

The situation from Influenza (From Virology Blog). Just the same 

The one issue with this work is that of undersampling. We know so little about the genomic diversity of this group of virus and currently have very little data to compare Schmallenberg to. What we need is to sequence a whole range of isolates from across all continents in order to truly answer the question of where this virus originated. 


And even then, this information will be of little use and may even be used to point the finger of blame. We need to hope that Schmallenberg doesn't come back again in the next couple of years and then if it does, we are ready for it this time. The only way this will happen is with increased global recognition and surveillance of these viruses. 

Reference:


Yanase, T., Kato, T., Aizawa, M., Shuto, Y., Shirafuji, H., Yamakawa, M., & Tsuda, T. (2012). Genetic reassortment between Sathuperi and Shamonda viruses of the genus Orthobunyavirus in nature: implications for their genetic relationship to Schmallenberg virus Archives of Virology DOI: 10.1007/s00705-012-1341-8

A virologist's take on the black death genome #microtwjc 2

The second paper in the Microbiology Twitter Journal Club (Tuesday the 22nd May 2012) is the paper out last year documenting the sequencing and assembly of the complete genome of a strain of Yersinia Pestis (plague) from a 14th Century burial site. It's open access so check it out here.


Here's a PBS news story (w/ interview with lead author as well):

Watch Reconstructing Black Death: Why Was Plague Microbe so Deadly? on PBS. See more from PBS NewsHour.

There's also an accompanying feature covering the history and background to Black Death research by Nature, here. Also includes some nice criticisms of this work too. There's also a Nature Blog article here. And here's New York Times article. There's a range of articles by Michelle Ziegler over at Contagions blog to have a look at. And finally before I forget, Vincent Racaniello's 'This Week in Microbiology' podcast covered it last year here.


Here's the video abstract from Nature:

A third dose of MMR is safe but do we need it?

It was recently reported - at the National Foundation for Infectious Diseases 15th Annual Conference on Vaccine Research - that the rate of adverse effects from a third dose of the measles, mumps and rubella (MMR) vaccine is the same as those of the second dose. This was conducted as part of a Centres for Disease Control study and led by Glen Abedi, an epidemiologist at the CDC and Masters student. I'm basing this on a media report of the conference as the paper has not yet been published. You can find more results here.


This is the first study to look at the safety of receiving a third dose of the vaccine in school children during an outbreak. The study has some obvious caveats but what it brings up is the question of whether we should extend 3-dose coverage to the population as a whole?


A mumps outbreak from 2009 to 2010 in and around New York City offered the CDC the chance to specifically look and see just how safe the administration of the third dose would be. In this outbreak - and in others - a very large percentage of those with clinical mumps had received two doses of MMR. We don't really know why, maybe it's a question of them getting a large dose of mumps, or maybe it's the vaccine not being perfect and inducing waning immunity.


They used this as a booster shot against the mumps virus in order to prevent further infection and spread from the community and to do so, they set up vaccination clinics in a number of school in the Orange County area of NYC. Those immunised were between 11 and 17 years old. These booster clinics have been set up before for mumps. These clinics are very money intensive and have reported to cost around $500/person. 


As a means to stem the tide of the outbreak, this three dose schedule worked and the rates of mumps infection dropped from 4.93/1000 to 0.13/1000. Although there was no reporting of antibody levels before and after the 3 doses. And we can't be sure whether the outbreak would have abruptly ended like this without vaccine intervention. One caveat with these kinds of studies is that they usually administer the dose late into the outbreak. If done earlier they may have completely controlled it's spread.


But to determine whether this was safe they had to send out questionnaires to the families of the kids, they consulted local clinics and they looked up the Vaccine Adverse Events Reporting System (VAERS). Over 90% of those immunised responded and only 115 reported adverse effects 2 weeks after vaccination. Those effects were only local pain/swelling at the injection site, muscle pain and dizziness/light-headedness. All the kinds of things that suggest that your immune system recognised the vaccine. Note that no cases of meningitis, glandular swelling  or orchitis were recognised, somewhat more serious effects of mumps vaccination in some cases.


This research highlights that in certain situations (a relatively small localised outbreak, with very targeted vaccination of schoolchildren) a third dose of MMR is safe. Of course if they wanted to definitively test this I think they would need a bigger sample size/diversity than the 1755 religious school kids. Remember also that they didn't report looking into levels of mumps immunity so time will tell whether these children were really protected and whether they may still get mumps in the next couple of years.


But the question now remains is whether or not we should extend three doses to the general population or even in cases of a localised outbreak. Mumps is a very infectious virus and hence you need very high levels of population protection to achieve herd immunity (estimated as high as 92%). In the U.S, those between 13 and 17 have an estimated 2-dose MMR coverage of 90.5% and the MMR vaccine uptake percentage in colleges etc is just shy of 90%. So maybe what this data says is that in general we should really focus on achieving very high levels of 2-dose MMR but in the cases of a mumps outbreak we could use a targeted third dose. If we didn't mind the cost. Maybe in the future to lower the costs, all schools/campuses will introduce a MMR catch-up when the new students start.


Another issue apparent is whether we need a new mumps vaccine. Clearly our current mumps vaccine has been amazingly effective to date but maybe it is not enough to completely eradicate the virus. This is something we will have to consider now that people are developing newer vaccines against the virus.



Centers for Disease Control and Prevention (CDC) (2010). Update: mumps outbreak - New York and New Jersey, June 2009-January 2010. MMWR. Morbidity and mortality weekly report, 59 (5), 125-9 PMID: 20150887

Viruses This Week in Bats

OK they're cute, but are they deadly?

I was lucky enough to appear alongside the guys over at This Week in Virology (thanks Vincent, Alan, Rich and Dickson) to discuss the recent publication of a paper (here in open access) which identified bats and rodents as potential animal reservoirs for a whole load of newly discovered RNA viruses, among other things. Check out the link above and enjoy what was an extremely fun and interesting hour and a half long experience. 

The paper, from a large group of authors right across the world (actually when you look at where they looked, it wasn't all that much of the globe but I guess it is a sample after all), looked specifically for paramyxoviruses in bats and in rodents. 

They picked paramyxoviruses because these viruses have been known to jump species from mammals into humans and other animals, they cause significant diseases (measles, mumps, respiratory infection and encephalitis and finally because I guess they had to focus somewhere. They actually tried unbiased 'deep sequencing' and quickly found it was heavily biased toward not finding paramyxoviruses. Possibly explaining the lack of paramyxovirus discovery in previous non-targeted efforts.

Their thinking was that these bats and rodents would have the potential to host a large number of viruses due to their high population sizes/densities, close contact with each other and potential to travel large distances (in the case of bats). Of course based on these criteria they could have looked in fish or birds but bats and rodents being mammals, there's a higher likelihood that their viruses could do really well in humans (although look at influenza and human metapneuomovirus). Although I bet you would find hundreds more if you explored the seas and the skies as opposed to the jungles.

They looked in over 10,000 individual animals from 15 places around the world, mostly in the tropics and were able identify 66 previously unknown 'species', more than doubling the potential number of potential paramyxoviruses previously known. They even identified the possibly first cousins of many of our deadly viruses, like mumps, nipah and respiratory syncytial virus. 

They then took this further and looked at how viruses like these grew in bats, whether they caused disease and were the excreted and transmitted within and between bat populations. Instead of exploring what viruses were simply present, this group was more interested in establishing whether bats acted as an animal reservoir as knowing this would be excellent from a public health perspective. For example, what areas/species should be protecting and avoided from human contact.

Also from a purely biological perspective, if we assume that these closely related viruses (for example the 'bat mumps' virus) are well adapted to bats and not to humans and then vice versa for the human viruses, then the similarities and differences in functions of each component of the virus should be illuminating understanding how viruses jump species.

#Microtwjc 1 - bacterial cell shape and pathogenesis

This is new ground for me as a virologist, writing about bacterial genetics and pathogenesis. But it's for a good cause - the cause of Microbiology Twitter Journal Club or #microtwjc. Set up by Zoonotica and encompassing a number of other microbiologists. This post serves background reading for the discussion on this paper on Tuesday the 8th May at 20:00 BST.

This paper aims to determine the role of bacterial shape/structure in how micro-organisms cause disease. I don't think they actually succeed in doing this as it's going to be a pretty complicated picture. But it does highlight a number of interesting points in bacterial genetics and pathogenesis, especially for an organism in which very little is really known.

Two very different structures - ultimately a single genetic change. But how?