Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

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

Increased larval mosquito densities from modified landuses in the Kapiti region, New Zealand: Vegetation, water quality, and predators as associated environmental factors

Landuse changes, including deforestation, agriculture, and urbanization, have coincided with an increase in vector-borne diseases worldwide. Landuse changes may alter mosquito populations by modifying the characteristics of aquatic larval habitats, but we still poorly understand the physical, chemical, and biological factors involved. We examined a total of 81 mosquito larval habitats for immature mosquitoes and 17 environmental variables in native forest, pastureland, and urbanland, at three locations in the Kapiti region, New Zealand. Significantly higher immature mosquito densities, predominantly of the endemic species Cx. pervigilans, were collected from urbanland and pastureland compared to native forest. Urbanland and pastureland habitats were mostly artificial containers compared to ground pools in native forest. Generalized linear modeling (GLM) revealed nine environmental variables that were significantly different between landuses. Of these variables, mosquito density was significantly (positively) correlated with bacteria and dissolved organic carbon. When location and date were controlled for in GLM, mosquito density was (negatively) related to the presence of vegetation and combined predators. The findings of this study support those from prior surveys in warmer climates suggesting greater mosquito-borne disease risk in anthropogenically-modified environments because of ecosystem disruption. Unlike most previous field-based work, this study suggests that in addition to habitat type, the presence of vegetation, water quality, and predators are also associated with mosquito density and may be involved in causal mechanisms. Urban containers and stock drinking troughs had high mosquito densities, suggesting that an initial step in directing control operations should be to focus on these habitats