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

Date Published: January 10, 2013

Publisher: Public Library of Science

Author(s): 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, Friedemann Weber.

http://doi.org/10.1371/journal.ppat.1003133

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.

Partial Text

Approximately 30 percent of all infectious diseases that emerged between 1990 and 2000 were caused by arthropod-borne viruses (arbovirus) [1]. 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.

SBV is a new emerging orthobunyavirus that has been associated with abortions and malformations in sheep and cattle. The Bunyaviridae include many viruses that have emerged or re-emerged in the last decade such as OROPV, Henan fever virus, Crimean-Congo hemorrhagic fever, RVFV, LCV and others [38]–[42]. SBV was isolated for the first time in Germany in October 2011 [3]. However, the virus probably entered Northwestern Europe in the border region of The Netherlands, Germany and Belgium [8] and subsequently spread rapidly to neighboring countries, including Luxembourg, France, Italy, Spain, Denmark and the United Kingdom. In this study, we have established an experimental platform that comprises both in vitro and in vivo systems to study SBV biology and pathogenesis.

 

Source:

http://doi.org/10.1371/journal.ppat.1003133

 

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