KOP VAN KOE, COWS ON THE MOVE, NRM, KOEIENKOPHi all

This week’s paper is another virology paper – Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host (Varela M, Schnettler E, Caporale M, Murgia C, Barry G, et al.  (2013) Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host. PLoS Pathog 9(1):e1003133.doi:10.1371/journal.ppat.1003133).

I don’t actually work with viruses – I will be spending the next week teaching myself some basic virology – but I am interested in new and emerging diseases so I was very pleased to see this paper out.

Author’s Summary

“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 Netherlands, Belgium, France and the United Kingdom. Very little is known about the biological properties of this virus and there is no vaccine available. In this study (i) we developed an approach (called reverse genetics) that allows the recovery of “synthetic” SBV under laboratory conditions; (ii) we developed a mouse model of infection for SBV; (iii) we showed that SBV replicates in neurons of experimentally infected mice similar to naturally infected lambs and calves; (iv) we developed viral mutants that are not as pathogenic as the original virus due to the inability to counteract the host cell defenses; and v) we identified mutations that are associated with increased virulence. This work provides the 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 highly effective vaccines.”

Abstract

“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.”

Discussion Points

  • Was the paper well written?
  • Were the methods appropriate and how useful will they be for future SBV/other virology work?
  • If this was your work what experiments would you do next?

I will try to get a blog post on this paper up asap and will link to it in the comments.  (I have also previously written about the virus, one post discussing the discovery of it and one post with some useful links and a podcast from the SGM.)

Happy reading everyone and I look forward to next week’s club, Tues 22nd Jan, 8pm GMT

Image

With thanks to CRV Arnhem for making this available via a Creative Commons licence http://commons.wikimedia.org/wiki/File:Koeienkoppen.jpg

Advertisements