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Martin Beer - One of the best experts on this subject based on the ideXlab platform.
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a genome wide crispr cas9 screen reveals the requirement of host cell sulfation for schmallenberg virus infection
Journal of Virology, 2020Co-Authors: Thiprampai Thamamongood, Martin Beer, Andrea Aebischer, Valentina Wagner, Max W Chang, Roland Elling, Christopher Benner, Adolfo Garciasastre, Georg Kochs, Martin SchwemmleAbstract:Schmallenberg virus (SBV) is an insect-transmitted Orthobunyavirus that can cause abortions and congenital malformations in the offspring of ruminants. Even though the two viral surface glycoproteins Gn and Gc are involved in host cell entry, the specific cellular receptors of SBV are currently unknown. Using genome-wide CRISPR-Cas9 forward screening, we identified 3'-phosphoadenosine 5'-phosphosulfate (PAPS) transporter 1 (PAPST1) as an essential factor for SBV infection. PAPST1 is a sulfotransferase involved in heparan sulfate proteoglycan synthesis encoded by the solute carrier family 35 member B2 gene (SLC35B2). SBV cell surface attachment and entry were largely reduced upon the knockout of SLC35B2, whereas the reconstitution of SLC35B2 in these cells fully restored their susceptibility to SBV infection. Furthermore, treatment of cells with heparinase diminished infection with SBV, confirming that heparan sulfate plays an important role in cell attachment and entry, although to various degrees, heparan sulfate was also found to be important to initiate infection by two other bunyaviruses, La Crosse virus and Rift Valley fever virus. Thus, PAPST1-triggered synthesis of cell surface heparan sulfate is required for the efficient replication of SBV and other bunyaviruses.IMPORTANCE SBV is a newly emerging Orthobunyavirus (family Peribunyaviridae) that has spread rapidly across Europe since 2011, resulting in substantial economic losses in livestock farming. In this study, we performed unbiased genome-wide CRISPR-Cas9 screening and identified PAPST1, a sulfotransferase encoded by SLC35B2, as a host entry factor for SBV. Consistent with its role in the synthesis of heparan sulfate, we show that this activity is required for efficient infection by SBV. A comparable dependency on heparan sulfate was also observed for La Crosse virus and Rift Valley fever virus, highlighting the importance of heparan sulfate for host cell infection by bunyaviruses. Thus, the present work provides crucial insights into virus-host interactions of important animal and human pathogens.
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Misinterpretation of Schmallenberg virus sequence variations: the sample material makes the difference
Virus Genes, 2019Co-Authors: Kerstin Wernike, Martin BeerAbstract:In recent reports about the molecular epidemiology of Schmallenberg virus (SBV), an Orthobunyavirus affecting ruminants, it was proposed that the observed sequence variability within the viral M-segment might be higher in sheep than in cattle. However, these analyses are highly biased by the sample material from which the publicly available sequences were generated. While from cattle predominantly blood samples from acutely infected animals were studied, the vast majority of ovine samples originate from malformed fetuses or newborn lambs. Therefore, the observed sequence variability is misinterpreted since the samples from malformed fetuses and lambs do not reflect circulating SBV.
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Orthobunyavirus spike architecture and recognition by neutralizing antibodies
Nature Communications, 2019Co-Authors: Jan Hellert, Kerstin Wernike, Andrea Aebischer, Ahmed Haouz, Emiliana Brocchi, Sven Reiche, Pablo Guardado-calvo, Martin BeerAbstract:Orthobunyaviruses (OBVs) form a distinct genus of arthropod-borne bunyaviruses that can cause severe disease upon zoonotic transmission to humans. Antigenic drift or genome segment re-assortment have in the past resulted in new pathogenic OBVs, making them potential candidates for causing emerging zoonoses in the future. Low-resolution electron cryo-tomography studies have shown that OBV particles feature prominent trimeric spikes, but their molecular organization remained unknown. Here we report X-ray crystallography studies of four different OBVs showing that the spikes are formed by an N-terminal extension of the fusion glycoprotein Gc. Using Schmallenberg virus, a recently emerged OBV, we also show that the projecting spike is the major target of the neutralizing antibody response, and provide X-ray structures in complex with two protecting antibodies. We further show that immunization of mice with the spike domains elicits virtually sterilizing immunity, providing fundamental knowledge essential in the preparation for potential newly emerging OBV zoonoses. Orthobunyaviruses (OBVs) cause severe disease in humans and farm animals, but the molecular basis for infection is not fully understood. Here, the authors present crystal structures of free and antibody-bound OBV envelope glycoproteins and show that their domains enable efficient immunization in a mouse model.
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Culicoides Biting Midges—Underestimated Vectors for Arboviruses of Public Health and Veterinary Importance
MDPI AG, 2019Co-Authors: Franziska Sick, Martin Beer, Helge Kampen, Kerstin WernikeAbstract:Culicoides biting midges, small hematophagous dipterans, are the demonstrated or putative vectors of multiple arboviruses of veterinary and public health importance. Despite its relevance in disease spread, the ceratopogonid genus Culicoides is still a largely neglected group of species, predominantly because the major human-affecting arboviruses are considered to be transmitted by mosquitoes. However, when a pathogen is detected in a certain vector species, a thorough search for further vectors often remains undone and, therefore, the relevant vector species may remain unknown. Furthermore, for many hematophagous arthropods, true vector competence is often merely suspected and not experimentally proven. Therefore, we aim to illuminate the general impact of Culicoides biting midges and to summarize the knowledge about biting midge-borne disease agents using the order Bunyavirales, the largest and most diverse group of RNA viruses, as an example. When considering only viruses evidentially transmitted by Culicoides midges, the Simbu serogroup (genus Orthobunyavirus) is presumably the most important group within the virus order. Its members are of great veterinary importance, as a variety of simbuviruses, e.g., the species Akabane Orthobunyavirus or Schmallenberg Orthobunyavirus, induces severe congenital infections in pregnant animals. The major zoonotic representative of this serogroup occurs in South and Central America and causes the so-called Oropouche fever, an acute febrile illness in humans
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A broad spectrum screening of Schmallenberg virus antibodies in wildlife animals in Germany
Veterinary Research, 2015Co-Authors: Susan Mouchantat, Kerstin Wernike, Bernd Hoffmann, Walburga Lutz, Rainer G. Ulrich, Konstantin Börner, Ulrich Wittstatt, Martin BeerAbstract:AbstractTo identify native wildlife species possibly susceptible to infection with Schmallenberg virus (SBV), a midge-transmitted Orthobunyavirus that predominantly infects domestic ruminants, samples from various free-living ruminants, but also carnivores, small mammals and wild boar were analyzed serologically. Before 2011, no SBV-specific antibodies were detectable in any of the tested species, thereafter, a large proportion of the ruminant population became seropositive, while every sample taken from carnivores or small mammals tested negative. Surprisingly, SBV-specific-antibodies were also present in a large number of blood samples from wild boar during the 2011/2012 and 2012/2013 hunting seasons. Hence, free-ranging artiodactyls may play a role as wildlife host.
Kerstin Wernike - One of the best experts on this subject based on the ideXlab platform.
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Misinterpretation of Schmallenberg virus sequence variations: the sample material makes the difference
Virus Genes, 2019Co-Authors: Kerstin Wernike, Martin BeerAbstract:In recent reports about the molecular epidemiology of Schmallenberg virus (SBV), an Orthobunyavirus affecting ruminants, it was proposed that the observed sequence variability within the viral M-segment might be higher in sheep than in cattle. However, these analyses are highly biased by the sample material from which the publicly available sequences were generated. While from cattle predominantly blood samples from acutely infected animals were studied, the vast majority of ovine samples originate from malformed fetuses or newborn lambs. Therefore, the observed sequence variability is misinterpreted since the samples from malformed fetuses and lambs do not reflect circulating SBV.
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Orthobunyavirus spike architecture and recognition by neutralizing antibodies
Nature Communications, 2019Co-Authors: Jan Hellert, Kerstin Wernike, Andrea Aebischer, Ahmed Haouz, Emiliana Brocchi, Sven Reiche, Pablo Guardado-calvo, Martin BeerAbstract:Orthobunyaviruses (OBVs) form a distinct genus of arthropod-borne bunyaviruses that can cause severe disease upon zoonotic transmission to humans. Antigenic drift or genome segment re-assortment have in the past resulted in new pathogenic OBVs, making them potential candidates for causing emerging zoonoses in the future. Low-resolution electron cryo-tomography studies have shown that OBV particles feature prominent trimeric spikes, but their molecular organization remained unknown. Here we report X-ray crystallography studies of four different OBVs showing that the spikes are formed by an N-terminal extension of the fusion glycoprotein Gc. Using Schmallenberg virus, a recently emerged OBV, we also show that the projecting spike is the major target of the neutralizing antibody response, and provide X-ray structures in complex with two protecting antibodies. We further show that immunization of mice with the spike domains elicits virtually sterilizing immunity, providing fundamental knowledge essential in the preparation for potential newly emerging OBV zoonoses. Orthobunyaviruses (OBVs) cause severe disease in humans and farm animals, but the molecular basis for infection is not fully understood. Here, the authors present crystal structures of free and antibody-bound OBV envelope glycoproteins and show that their domains enable efficient immunization in a mouse model.
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Culicoides Biting Midges—Underestimated Vectors for Arboviruses of Public Health and Veterinary Importance
MDPI AG, 2019Co-Authors: Franziska Sick, Martin Beer, Helge Kampen, Kerstin WernikeAbstract:Culicoides biting midges, small hematophagous dipterans, are the demonstrated or putative vectors of multiple arboviruses of veterinary and public health importance. Despite its relevance in disease spread, the ceratopogonid genus Culicoides is still a largely neglected group of species, predominantly because the major human-affecting arboviruses are considered to be transmitted by mosquitoes. However, when a pathogen is detected in a certain vector species, a thorough search for further vectors often remains undone and, therefore, the relevant vector species may remain unknown. Furthermore, for many hematophagous arthropods, true vector competence is often merely suspected and not experimentally proven. Therefore, we aim to illuminate the general impact of Culicoides biting midges and to summarize the knowledge about biting midge-borne disease agents using the order Bunyavirales, the largest and most diverse group of RNA viruses, as an example. When considering only viruses evidentially transmitted by Culicoides midges, the Simbu serogroup (genus Orthobunyavirus) is presumably the most important group within the virus order. Its members are of great veterinary importance, as a variety of simbuviruses, e.g., the species Akabane Orthobunyavirus or Schmallenberg Orthobunyavirus, induces severe congenital infections in pregnant animals. The major zoonotic representative of this serogroup occurs in South and Central America and causes the so-called Oropouche fever, an acute febrile illness in humans
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Virological and Serological Responses of Sheep and Cattle to Experimental Schmallenberg Virus Infection.
Vector-borne and Zoonotic Diseases, 2018Co-Authors: Abaineh D Endalew, Kerstin Wernike, Igor Morozov, A. Sally Davis, Natasha N. Gaudreault, Bhupinder Bawa, Mark G. Ruder, Barbara S. Drolet, D. Scott Mcvey, Vinay ShivannaAbstract:Schmallenberg virus (SBV) is an Orthobunyavirus in the Simbu serogroup that emerged in Germany in late 2011 and was mostly associated with a mild transient disease of sheep and cattle. SBV is trans...
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A broad spectrum screening of Schmallenberg virus antibodies in wildlife animals in Germany
Veterinary Research, 2015Co-Authors: Susan Mouchantat, Kerstin Wernike, Bernd Hoffmann, Walburga Lutz, Rainer G. Ulrich, Konstantin Börner, Ulrich Wittstatt, Martin BeerAbstract:AbstractTo identify native wildlife species possibly susceptible to infection with Schmallenberg virus (SBV), a midge-transmitted Orthobunyavirus that predominantly infects domestic ruminants, samples from various free-living ruminants, but also carnivores, small mammals and wild boar were analyzed serologically. Before 2011, no SBV-specific antibodies were detectable in any of the tested species, thereafter, a large proportion of the ruminant population became seropositive, while every sample taken from carnivores or small mammals tested negative. Surprisingly, SBV-specific-antibodies were also present in a large number of blood samples from wild boar during the 2011/2012 and 2012/2013 hunting seasons. Hence, free-ranging artiodactyls may play a role as wildlife host.
Richard M. Elliott - One of the best experts on this subject based on the ideXlab platform.
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The Antiviral RNAi Response in Vector and Non-vector Cells against Orthobunyaviruses.
Public Library of Science (PLoS), 2017Co-Authors: Isabelle Dietrich, Richard M. Elliott, Xiaohong Shi, Alain Kohl, Melanie Mcfarlane, Mick Watson, Anne-lie Blomström, Jessica K Skelton, Esther SchnettlerAbstract:BACKGROUND:Vector arthropods control arbovirus replication and spread through antiviral innate immune responses including RNA interference (RNAi) pathways. Arbovirus infections have been shown to induce the exogenous small interfering RNA (siRNA) and Piwi-interacting RNA (piRNA) pathways, but direct antiviral activity by these host responses in mosquito cells has only been demonstrated against a limited number of positive-strand RNA arboviruses. For bunyaviruses in general, the relative contribution of small RNA pathways in antiviral defences is unknown. METHODOLOGY/PRINCIPAL FINDINGS:The genus Orthobunyavirus in the Bunyaviridae family harbours a diverse range of mosquito-, midge- and tick-borne arboviruses. We hypothesized that differences in the antiviral RNAi response in vector versus non-vector cells may exist and that could influence viral host range. Using Aedes aegypti-derived mosquito cells, mosquito-borne Orthobunyaviruses and midge-borne Orthobunyaviruses we showed that bunyavirus infection commonly induced the production of small RNAs and the effects of the small RNA pathways on individual viruses differ in specific vector-arbovirus interactions. CONCLUSIONS/SIGNIFICANCE:These findings have important implications for our understanding of antiviral RNAi pathways and Orthobunyavirus-vector interactions and tropism
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Bunyamwera Orthobunyavirus glycoprotein precursor is processed by cellular signal peptidase and signal peptide peptidase
Proceedings of the National Academy of Sciences of the United States of America, 2016Co-Authors: Xiaohong Shi, Catherine H. Botting, Mark Niglas, Benjamin Brennan, Sally L. Shirran, Agnieszka M. Szemiel, Richard M. ElliottAbstract:The M genome segment of Bunyamwera virus (BUNV)—the prototype of both the Bunyaviridae family and the Orthobunyavirus genus—encodes the glycoprotein precursor (GPC) that is proteolytically cleaved to yield two viral structural glycoproteins, Gn and Gc, and a nonstructural protein, NSm. The cleavage mechanism of Orthobunyavirus GPCs and the host proteases involved have not been clarified. In this study, we investigated the processing of BUNV GPC and found that both NSm and Gc proteins were cleaved at their own internal signal peptides (SPs), in which NSm domain I functions as SPNSm and NSm domain V as SPGc. Moreover, the domain I was further processed by a host intramembrane-cleaving protease, signal peptide peptidase, and is required for cell fusion activities. Meanwhile, the NSm domain V (SPGc) remains integral to NSm, rendering the NSm topology as a two-membrane-spanning integral membrane protein. We defined the cleavage sites and boundaries between the processed proteins as follows: Gn, from residue 17–312 or nearby residues; NSm, 332–477; and Gc, 478–1433. Our data clarified the mechanism of the precursor cleavage process, which is important for our understanding of viral glycoprotein biogenesis in the genus Orthobunyavirus and thus presents a useful target for intervention strategies.
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Flexibility of Bunyavirus Genomes: Creation of an Orthobunyavirus with an Ambisense S Segment
Journal of Virology, 2015Co-Authors: Ingeborg Van Knippenberg, Richard M. ElliottAbstract:The Bunyamwera (BUNV) Orthobunyavirus NSs protein has proven a challenge to study in the context of viral infection. NSs is encoded in a reading frame that overlaps that of the viral nucleocapsid (N) protein thus limiting options for mutagenesis. In addition, NSs is poorly immunogenic, and antibodies only work in certain techniques while the protein itself is subject to proteasomal degradation. In order to generate a virus that expresses NSs independently of N, an ambisense S RNA segment was designed by mutating the 5′- and 3′-terminal nucleotide sequences. These mutations were previously shown to alter promoter activity so that both replication and transcription were promoted from both the genome and the antigenome RNAs (J. N. Barr et al., J. Virol. 79:12602–12607, 2005). As proof of principle, a recombinant BUNV was created that expressed green fluorescent protein (GFP) in the ambisense orientation. GFP expression was detected throughout at least 10 passages. Recombinant BUNV encoding epitope-tagged versions of NSs in the ambisense orientation expressed NSs via a subgenomic mRNA, and two viruses grew to titers only modestly lower than parental rBUNdelNSs2 virus. The ambisense viruses were temperature sensitive, and NSs was shown to localize to both the nucleus and the cytoplasm during infection. These viruses will be useful in further studies on structure-function relationships of the Orthobunyavirus NSs protein. IMPORTANCE Bunyamwera virus (BUNV) is the type species and model system for both the family Bunyaviridae and the genus Orthobunyavirus, a group that includes many significant human and animal pathogens. Studying the basic molecular biology of these viruses is of great importance to underpin research into vaccines and antivirals. We demonstrate here the plasticity of the BUNV genome by generating recombinant viruses where the normal negative-sense S segment has been converted into an ambisense segment, allowing independent expression of either a foreign gene (green fluorescent protein) or the viral nonstructural NSs protein. These new reagents will allow detailed investigation of NSs, the Orthobunyavirus interferon antagonist.
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Orthobunyaviruses: recent genetic and structural insights
Nature Reviews Microbiology, 2014Co-Authors: Richard M. ElliottAbstract:Orthobunyaviruses are arthropod-transmitted viruses that are characterized by a tripartite, negative-sense RNA genome. Some viruses in this family are associated with diseases in humans (such as fever and encephalitis) and domesticated animals (including abortion and teratogenic effects in offspring). Schmallenberg virus, which is a recently emerged member of the family, caused a disease outbreak in domesticated animals in Europe in 2012–2013. Viral replication occurs in the cytoplasm of infected cells and viruses mature by budding in the Golgi complex. Although infection of mammalian cells usually results in cell death, replication in arthropod vector cells is not cytopathic and these cells become persistently infected. Viral mRNA synthesis is primed by capped oligonucleotides that are derived from host cell mRNAs in a process that is known as cap snatching. The endonuclease activity that is responsible for generating the primers is contained in the amino-terminal domain of the viral RNA-dependent RNA polymerase protein. The three-dimensional structure of the viral N (nucleocapsid) protein shows that it forms a tetramer that contains a novel fold with a central, positively charged groove that binds to the viral RNA. The viral non-structural protein NSs is the major virulence factor and antagonizes the host innate immune response by causing global inhibition of RNA polymerase II-mediated transcription. Possession of a segmented genome enables Orthobunyaviruses to evolve rapidly by segment reassortment during mixed infections. Reassortment occurs widely in nature and reassortant viruses can have dramatically altered properties, such as increased virulence. Little is known about the burden of Orthobunyavirus disease and there is a need for improved global surveillance to monitor Orthobunyavirus activity. Orthobunyaviruses are transmitted by arthropod vectors and can infect humans, animals and crops. In this Review, Elliott describes recent genetic and structural advances that have revealed important insights into the composition of Orthobunyavirus virions, viral transcription and replication, and viral interactions with the host innate immune response. Orthobunyaviruses, which have small, tripartite, negative-sense RNA genomes and structurally simple virions composed of just four proteins, can have devastating effects on human health and well-being, either by causing disease in humans or by causing disease in livestock and crops. In this Review, I describe the recent genetic and structural advances that have revealed important insights into the composition of Orthobunyavirus virions, viral transcription and replication and viral interactions with the host innate immune response. Lastly, I highlight outstanding questions and areas of future research.
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Bunyaviruses and innate immunity.
Cellular Signaling and Innate Immune Responses to RNA Virus Infections, 2014Co-Authors: Friedemann Weber, Richard M. ElliottAbstract:This chapter summarizes the current state of knowledge about how the viruses of the Bunyaviridae succeed in establishing infection in the face of a powerful innate immune system. Members of the Bunyaviridae are classified into five genera: Orthobunyavirus, Phlebovirus, Hantavirus, Nairovirus, and Tospovirus. In this chapter the term ‘’bunyavirus‘’ refers to a member of the Bunyaviridae family, while the terms ‘’Orthobunyavirus‘’ ‘’phlebovirus‘’ refer to viruses in the eponymous genus. A well-established animal model for pathogenicity of arthropod-transmitted bunyaviruses does exist for La Crosse virus (LACV) virus in mice. Just as it is described for crimean-Congo hemorrhagic fever virus (CCHFV), high levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are present in hantavirus patients. A similar scenario is conceivable for those bunyaviruses that use arthropods as vectors. The first interferon (IFN) antagonists described for bunyaviruses were the NSs proteins of the Orthobunyavirus BUNV and the phlebovirus RVFV. Apparently, as bunyaviruses replicate in the cytoplasm and do not need ongoing cellular transcription for cap-snatching, blocking RNA polymerase II (RNAP II) function by NSs is the method of choice for Orthobunyaviruses and phleboviruses to counteract innate immune responses. Despite the significant economic and medical impact of the huge RNA virus family, the interactions of bunyaviruses with the innate immune system are only incompletely understood. Thus, a better understanding of the interplay between bunyaviruses and the innate immune response, as with most other viruses, can help in the design of new strategies for prevention and therapy.
Franz Josef Conraths - One of the best experts on this subject based on the ideXlab platform.
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Schmallenberg virus-Two years of experiences
Preventive Veterinary Medicine, 2014Co-Authors: Kerstin Wernike, Horst Schirrmeier, Franz Josef Conraths, Gina Zanella, Harald Granzow, Kristel Gache, Stephen Valas, Christoph Staubach, Philippe Marianneau, Franziska KraatzAbstract:In autumn 2011, a novel species of the genus Orthobunyavirus of the Simbu serogroup was discovered close to the German/Dutch border and named Schmallenberg virus (SBV). Since then, SBV has caused a large epidemic in European livestock. Like other viruses of the Simbu serogroup, SBV is transmitted by insect vectors. Adult ruminants may show a mild transient disease, while an infection during a critical period of pregnancy can lead to severe congenital malformation, premature birth or stillbirth. The current knowledge about the virus, its diagnosis, the spread of the epidemic, the impact and the possibilities for preventing infections with SBV is described and discussed.
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schmallenberg virus a novel Orthobunyavirus emerging in europe
Epidemiology and Infection, 2013Co-Authors: Martin Beer, Franz Josef Conraths, W.h.m. Van Der PoelAbstract:In 2011, a novel Orthobunyavirus of the Simbu serogroup, the Schmallenberg virus (SBV), was discovered using a metagenomic approach. SBV caused a large epidemic in Europe in ruminants. As with related viruses such as Akabane virus, it appears to be transmitted by biting midges. Transplacental infection often results in the birth of malformed calves, lambs and goat kids. In more than 5000 farms in Germany, The Netherlands, Belgium, France, UK, Italy, Spain, Luxembourg, Denmark and Switzerland acute infections of adult ruminants or malformed SBV-positive offspring were detected, and high seroprevalences were seen in adult ruminants in the core regions in The Netherlands, Germany and Belgium. The discovery of SBV, the spread of the epidemic, the role of vectors, the impact on livestock, public health issues, SBV diagnosis and measures taken are described in this review. Lessons to be learned from the Schmallenberg virus epidemic and the consequences for future outbreaks are discussed.
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‘Schmallenberg virus’ – a novel Orthobunyavirus emerging in Europe
Epidemiology and Infection, 2012Co-Authors: Martin Beer, Franz Josef Conraths, W.h.m. Van Der PoelAbstract:In 2011, a novel Orthobunyavirus of the Simbu serogroup, the Schmallenberg virus (SBV), was discovered using a metagenomic approach. SBV caused a large epidemic in Europe in ruminants. As with related viruses such as Akabane virus, it appears to be transmitted by biting midges. Transplacental infection often results in the birth of malformed calves, lambs and goat kids. In more than 5000 farms in Germany, The Netherlands, Belgium, France, UK, Italy, Spain, Luxembourg, Denmark and Switzerland acute infections of adult ruminants or malformed SBV-positive offspring were detected, and high seroprevalences were seen in adult ruminants in the core regions in The Netherlands, Germany and Belgium. The discovery of SBV, the spread of the epidemic, the role of vectors, the impact on livestock, public health issues, SBV diagnosis and measures taken are described in this review. Lessons to be learned from the Schmallenberg virus epidemic and the consequences for future outbreaks are discussed.
Marietjie Venter - One of the best experts on this subject based on the ideXlab platform.
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Reverse Genetics System for Shuni Virus, an Emerging Orthobunyavirus with Zoonotic Potential.
Viruses, 2020Co-Authors: Judith Oymans, Marietjie Venter, Paul J. Wichgers Schreur, Sophie Van Oort, R.p.m. Vloet, Gorben P. Pijlman, Monique M. Van Oers, Jeroen KortekaasAbstract:The genus Orthobunyavirus (family Peribunyaviridae, order Bunyavirales) comprises over 170 named mosquito- and midge-borne viruses, several of which cause severe disease in animals or humans. Their three-segmented genomes enable reassortment with related viruses, which may result in novel viruses with altered host or tissue tropism and virulence. One such reassortant, Schmallenberg virus (SBV), emerged in north-western Europe in 2011. Shuni virus (SHUV) is an Orthobunyavirus related to SBV that is associated with neurological disease in horses in southern Africa and recently caused an outbreak manifesting with neurological disease and birth defects among ruminants in Israel. The zoonotic potential of SHUV was recently underscored by its association with neurological disease in humans. We here report a reverse genetics system for SHUV and provide first evidence that the non-structural (NSs) protein of SHUV functions as an antagonist of host innate immune responses. We furthermore report the rescue of a reassortant containing the L and S segments of SBV and the M segment of SHUV. This novel reverse genetics system can now be used to study SHUV virulence and tropism, and to elucidate the molecular mechanisms that drive reassortment events.
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Orthobunyavirus Antibodies Among Humans in Selected Parts of the Rift Valley and Northeastern Kenya
Vector-borne and Zoonotic Diseases, 2015Co-Authors: Collins Odhiambo, Robert Swanepoel, Marietjie Venter, Rosemary SangAbstract:Abstract Ngari, Bunyamwera, Ilesha, and Germiston viruses are among the mosquito-borne human pathogens in the Orthobunyavirus genus, family Bunyaviridae, associated with febrile illness. Although the four Orthobunyaviruses have been isolated from mosquito and/or tick vectors sampled from different geographic regions in Kenya, little is known of human exposure in such areas. We conducted a serologic investigation to determine whether Orthobunyaviruses commonly infect humans in Kenya. Orthobunyavirus-specific antibodies were detected by plaque reduction neutralization tests in 89 (25.8%) of 345 persons tested. Multivariable analysis revealed age and residence in northeastern Kenya as risk factors. Implementation of acute febrile illness surveillance in northeastern Kenya will help to detect such infections.
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Genomic and phylogenetic characterization of Shuni virus
Archives of Virology, 2014Co-Authors: Charmaine Eeden, Frank Harders, Jeroen Kortekaas, Alex Bossers, Marietjie VenterAbstract:Shuni virus (SHUV), a member of the genus Orthobunyavirus , has in a recent study been associated with neurological disease in horses in South Africa. After its first isolation in 1966 from an asymptomatic bovine, very little attention was given to the genetic characterisation of SHUV. The association of SHUV with severe neurological disease in several horses in South Africa prompted us to determine the full genome sequence of a horse neurovirulent isolate to compare it to other members of the genus Orthobunyavirus , as well as the partially sequenced genome of the prototype SHUV strain. The availability of a full genome sequence will facilitate the development of a reverse genetics system to study SHUV molecular biology and pathogenesis.