Schmallenberg in sheep, a variable virus

4416794415_5bc163c831ResearchBlogging.orgIn 2011, a new animal virus was detected in the German town of Schmallenberg. This virus, which infects sheep and cows, is now sweeping across Europe and was first identified in the UK in 2012. In a new paper published in the Journal of General Virology, researchers in Belgium have found an area of the virus’s genome that is very prone to mutation.

Schmallenberg virus (SBV) belongs to the genus Orthobunyavirus, which contains several other viruses of veterinary importance. It causes a relatively mild or symptomless infection in adult cows or sheep, but can cross the placental barrier and cause serious congenital malformations or stillbirth in calves and lambs. SBV is an Arbovirus, transmitted between animals by biting insects. DEFRA suggest that the virus was bought to the UK by infected midges being blown across the Channel.

New research, led by Dr Benoît Muylkens, looked at the genetic variation of SBV after it infected the sheep flock at the University of Namur, Belgium. Dr Muylkens and colleagues compared the genomes of two SBV samples isolated from the nervous systems of two stillborn lambs to see how similar the viruses were. They found a high level of variability between the two samples, with the majority of differences found in a specific region of the SBV genome described by the authors as ‘hypervariable’. This region, which represents around ten per cent of the viral genome, had over half of the genetic changes.

As Dr Muylkens told me, “It was amazing to see how two viruses, isolated at the same time, from the same outbreak in a single herd, were so different. The two infected ewes  came from a subgroup in the herd; they lived very close together”.

Curiously, each of the samples showed more similarity to  the first sequenced SBV virus – isolated in Germany the previous year– than they did to each other.

SBV’s variation can be explained by its genetic material, which is RNA, rather than DNA. Like a great many other RNA viruses, the protein machinery that SBV uses to copy its genome lacks any proofreading ability. If a mistake happens while the RNA is being replicated – the wrong nucleotide being incorporated, for example – the mistake is permanent, meaning that every generation is potentially different from the one that preceded it.

The hypervariable region where most of the changes occurred was found in a gene encoding a glycoprotein that spikes out from the surface of the virus. Glycoproteins help viruses attach to, and enter, host cells; having one that is constantly changing may have several benefits to SBV.

Surface glycoproteins are often targets for the immune system, so having one that constantly changes might help SBV evade the host’s defences. Additionally, the changes might help the virus find new attachment sites on host cells.

In this work, the researchers grew several generations of SBV in vitro and showed that variability was found in the genome even in the absence of immune system pressure, suggesting that the changes in surface glycoprotein are not purely a method of immune system avoidance.

This work on SBV is important as it shows how the virus behaves in real life conditions. The researchers are now investigating the differences between the viruses in this study and those taken from the flock after a second infection that occurred a year later. That SBV can reinfect a previously exposed population suggests that it has changed enough to avoid the immune system. This is bad news, particularly as no vaccine yet exists.

Dr Muylkens explains, “Europe is now probably infected in an endemic fashion. I think the situation will be different with SBV compared to Blue Tongue Virus, which arrived in 2006. After a few years of vaccination we could manage it – now it appears to be absent in Europe. I’m not sure we’ll be so quick to manage SBV.”

Benjamin Thompson

Reference:

Coupeau, D., Claine, F., Wiggers, L., Kirschvink, N., & Muylkens, B. (2013). In vivo and in vitro identification of a hypervariable region in Schmallenberg virus Journal of General Virology DOI: 10.1099/vir.0.051821-0

Image Credit: Mark Bridge on Flickr
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