Manipulating the Schmallemberg virus genome to understand how it causes disease
Scottish researchers have developed methods to synthesize and change the genome of a recently discovered virus, in a bid to understand how it induces disease among livestock such as cattle, sheep and goats.
The research, led by Massimo Palmarini and Alain Kohl at the MRC Centre for Virus Research at the University of Glasgow, has laid bare important ways by which the Schmallenberg virus (SBV) causes disease and has paved the way for future development of new vaccines. The full report about the study publishes on January 10 in the Open Access journal, PLOS Pathogens.
SBV is of great concern because it causes stillbirths, abortions and fetal defects in pregnant cows and ewes. It has spread rapidly throughout Europe since its discovery in Germany in October 2011.
Palmarini, Director of Centre for Virus Research at the University of Glasgow, said: “insect-borne viruses, known as ‘arboviruses’, are increasingly becoming a problem throughout the world, whereas years ago they were limited mainly to the tropical areas of the globe.
“The spread of arboviruses is probably the result of several factors including increase in travelling and commercial exchanges, climate and ecological changes, and increased livestock production. This study will help us to understand how Schmallenberg virus works, but it can also serve as an example for other related viruses that may emerge in the future.”
The new research describes the molecular biological methods used to design and assemble the viral ‘genome’ completely in a test tube in a form that can be easily introduced and replicated in cultured cells. From these cells the researchers recovered the virus with identical infection properties to the "natural" SBV.
This approach, known as ‘reverse genetics’, allowed them to control the viral genome and identify a gene (called NSs) involved in protecting the virus against the immune response of infected animals. The researchers then made viruses missing the NSs gene. They discovered that, without the NSs gene, the virus adversely affected mice in the laboratory less than the virus containing the NSs gene.
Researchers also discovered that SBV rapidly grows in the brain and spinal cord of aborted lambs and calves. The virus prefers to infect neuron cells, which explains why it infects and damages the brain. This also results in muscular defects such as abnormally flexed legs often seen in stillborn animals when virus is transmitted from an SBV infected mother to the calves or lambs in the uterus during pregnancy.
SBV can be transmitted to livestock when they are bitten by insects such as midges which carry the virus. These insects control the viral infection by mounting a complex immune response meaning they themselves are not adversely affected by the virus. Recent work led by Alain Kohl and Esther Schnettler, published in the Journal of Virology, gives the first ever insights into how midges themselves respond to viruses such as SBV. This work may help inform the development of novel control strategies that target the insect rather than the animal.