Schmallenberg Virus Pathogenesis and Tropism

Approximately 30 percent of all infectious diseases that emerged between 1990 and 2000 were caused by arthropod-borne viruses (arboviruses). This is probably the result of a combination of factors including a dramatic increase in travelling and commercial exchanges, climate and ecological changes and increased livestock production. In addition, changes in trading and commercial policies have created optimal conditions for the movement of infected vertebrate hosts and invertebrate vectors over wide geographical areas.

Schmallenberg virus (SBV) was discovered in Germany (near the town of Schmallenberg) in November 2011 and since then has been found to be the cause of malformations and stillbirths in ruminants. SBV has spread very rapidly to many European countries including the United Kingdom. Very little is known about the biological properties of this virus and there is no vaccine available. In this study researchers developed an approach (called reverse genetics) that allows the recovery of “synthetic” SBV under laboratory conditions. They also developed a mouse model of infection for SBV and showed that SBV replicates in neurons of experimentally infected mice similar to naturally infected lambs and calves. Using thes tools they created SBV mutants that are not as pathogenic as the original virus due to the inability to counteract the host cell defences.This work provides important experimental tools to understand how this newly emerged virus causes disease in ruminants. In addition, it will now be possible to manipulate the SBV genome in order to develop effective vaccines.

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Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host. (2013) PLoS Pathog 9(1): e1003133. doi:10.1371/journal.ppat.1003133
Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV.

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