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

Virus-induced congenital malformations in cattle

Diagnosing the cause of bovine congenital malformations (BCMs) is challenging for bovine veterinary practitioners and laboratory diagnosticians as many known as well as a large number of not-yet reported syndromes exist. Foetal infection with certain viruses, including bovine virus diarrhea virus (BVDV), Schmallenberg virus (SBV), blue tongue virus (BTV), Akabane virus (AKAV), or Aino virus (AV), is associated with a range of congenital malformations. It is tempting for veterinary practitioners to diagnose such infections based only on the morphology of the defective offspring. However, diagnosing a virus as a cause of BCMs usually requires laboratory examination and even in such cases, interpretation of findings may be challenging due to lack of experience regarding genetic defects causing similar lesions, even in cases where virus or congenital antibodies are present. Intrauterine infection of the foetus during the susceptible periods of development, i.e. around gestation days 60–180, by BVDV, SBV, BTV, AKAV and AV may cause malformations in the central nervous system, especially in the brain. Brain lesions typically consist of hydranencephaly, porencephaly, hydrocephalus and cerebellar hypoplasia, which in case of SBV, AKAV and AV infections may be associated by malformation of the axial and appendicular skeleton, e.g. arthrogryposis multiplex congenita. Doming of the calvarium is present in some, but not all, cases. None of these lesions are pathognomonic so diagnosing a viral cause based on gross lesions is uncertain. Several genetic defects share morphology with virus induced congenital malformations, so expert advice should be sought when BCMs are encountered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-015-0145-8) contains supplementary material, which is available to authorized users

Isolation of a new rhabdovirus in Australia related to Tibrogargan virus

A virus isolated from the blood of a healthy steer and designated DPP53 was shown to have rhabdovirus morphology. Although DPP53 virus was antigenically related to Tibrogargan virus by reciprocal immunofluorescence and neutralization tests, the viruses were distinguishable by neutralization tests. DPP53 virus contained RNA and was sensitive to both ether and chloroform. The geographical distribution of neutralizing antibody to DPP53 virus in Australian cattle corresponded to the distribution of Culicoides brevitarsis indicating that this virus may be arthropod-borne with this midge as a possible vector. Antibody to DPP53 virus was detected in serum from cattle, buffalo, dogs and one horse, but not in serum from deer, pigs, humans or wallabies. Highest virus titres were obtained by growth in Vero and BHK21 cell cultures, but the virus could also be grown in Aedes albopictus cell cultures. Higher virus titres were obtained when the multiplicity of infection was low. The name advanced for DPP53 virus is 'Coastal Plains' virus

The effect of disability on the needs of caregivers

Purpose - The perception among carers and health professionals is that the health care system remains limited in its effectiveness and accessibility to non-institutionalized people with a mental illness. The purpose of this paper is to determine the effect of the care recipient's main disabling condition (either physical or mental) on the carer's perceived need for assistance in their role as carer. Design/methodology/approach - Based on the data collected from the Australian Survey of Disability, Ageing and Carers, the investigation involves the non-institutionalized recipients of care with profound and severe disabilities, aged 15 years and over, residing in private dwellings and their primary informal carers. Findings - Regression analysis reveals that carers of those with a mental disability are 2.7 times more likely to report care needs unmet compared to carers of those with a physical disability. Further analysis using interactions shows that carers who are the adult children of mentally disabled parents report a comparatively very large amount of perceived unmet need. Originality/value - If equity ismeasured in terms of perceived need rather than finite resources a case is made that primary carers of people with a mental disability experience greater burdens in care.Griffith Business School, Department of Accounting, Finance and EconomicsFull Tex

Caring for people with a mental disability at home: Australian carers' perceptions of service provision

This study investigates carer perceptions of the adequacy of assistance received by comparing two populations: those with a mental disability and those with a physical disability in Australia by using data representing 12.5% of the total population. This very large sample provides robust evidence for the study's findings. Of those caring for individuals with severe core disabilities, 21.6% of those with a mental disability compared to only 8.3% of carers of those with a physical disability reported inadequate service assistance. Greater involvement of consumers and their families in health care service planning will provide opportunities to deliver more appropriate services and enhance equities within this sector

Size Matters: The Link between CEO Remuneration, Firm Size and Firm Performance Moderated by Remuneration Committee Independence

CEO compensation, Remuneration committee independence, Firm size, Firm performance.

The effect of disability on the needs of caregivers

Purpose: The perception among carers and health professionals is that the health care system remains limited in its effectiveness and accessibility to non-institutionalized people with a mental illness. The purpose of this paper is to determine the effect of the care recipient's main disabling condition (either physical or mental) on the carer's perceived need for assistance in their role as carer. Design/methodology/approach: Based on the data collected from the Australian Survey of Disability, Ageing and Carers, the investigation involves the non-institutionalized recipients of care with profound and severe disabilities, aged 15 years and over, residing in private dwellings and their primary informal carers. Findings: Regression analysis reveals that carers of those with a mental disability are 2.7 times more likely to report care needs unmet compared to carers of those with a physical disability. Further analysis using interactions shows that carers who are the adult children of mentally disabled parents report a comparatively very large amount of perceived unmet need. Originality/value: If equity is measured in terms of perceived need rather than finite resources a case is made that primary carers of people with a mental disability experience greater burdens in care. © Emerald Group Publishing Limited

A blocking ELISA for the detection of specific antibodies to bovine ephemeral fever virus

A blocking ELISA (B/ELISA) for detecting antibodies to bovine ephemeral fever virus (BEFV) in cattle is described. In this test, the binding capacity of a monoclonal antibody specific for an epitope on antigenic site G1 of the BEF virus glycoprotein is blocked in the presence of positive serum. The sensitivity of the B/ELISA was compared with the virus neutralisation (VN) test using a total of 380 sera from cattle. Of these, 118 were from an area known to be free of bovine ephemeral fever, 181 from naturally and experimentally BEFV-infected cattle, 33 sequential serum samples from a sentinel steer from which Berrimah virus (BERV) had been isolated, 9 from a sentinel cow from which Kimberley virus (KIMV) was isolated and a panel of 39 sera supplied as a blind trial. The B/ELISA results overall compared favourably with those of the VN tests. The monospecificity of the test was demonstrated using hyperimmune mouse ascitic fluid to other BEF serogroup viruses, namely KIM and BER viruses and the results showed no significant cross-reaction. The greater simplicity and sensitivity of the test when compared with the VN test makes it the preferred test for the diagnosis and monitoring of clinical bovine ephemeral fever