Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host

• DOI: 10.1371/journal.ppat.1003133
• Publication Date: 2013-01-10T21:53:38Z
• Authors: Mariana Varela; Esther Schnettler; Marco Caporale; Claudio Murgia; Gerald Barry; Melanie McFarlane; Eva McGregor; Ilaria M. Piras; Andrew Shaw; Catherine Lamm; Anna Janowicz; Martin Beer; Mandy Glass; Vanessa Herder; Kerstin Hahn; Wolfgang Baumgärtner; Alain Kohl; Massimo Palmarini
• Keywords: Orthobunyavirus; Tissue tropism

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