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Journal of Virology Mar 2022With more than 80 members worldwide, the genus in the family is a large genus of enveloped RNA viruses, many of which are emerging pathogens in humans and livestock....
With more than 80 members worldwide, the genus in the family is a large genus of enveloped RNA viruses, many of which are emerging pathogens in humans and livestock. How orthobunyaviruses (OBVs) penetrate and infect mammalian host cells remains poorly characterized. Here, we investigated the entry mechanisms of the OBV Germiston (GERV). Viral particles were visualized by cryo-electron microscopy and appeared roughly spherical with an average diameter of 98 nm. Labeling of the virus with fluorescent dyes did not adversely affect its infectivity and allowed the monitoring of single particles in fixed and live cells. Using this approach, we found that endocytic internalization of bound viruses was asynchronous and occurred within 30 to 40 min. The virus entered Rab5a-positive (Rab5a) early endosomes and, subsequently, late endosomal vacuoles containing Rab7a but not LAMP-1. Infectious entry did not require proteolytic cleavage, and endosomal acidification was sufficient and necessary for viral fusion. Acid-activated penetration began 15 to 25 min after initiation of virus internalization and relied on maturation of early endosomes to late endosomes. The optimal pH for viral membrane fusion was slightly below 6.0, and penetration was hampered when the potassium influx was abolished. Overall, our study provides real-time visualization of GERV entry into host cells and demonstrates the importance of late endosomal maturation in facilitating OBV penetration. Orthobunyaviruses (OBVs), which include La Crosse, Oropouche, and Schmallenberg viruses, represent a growing threat to humans and domestic animals worldwide. Ideally, preventing OBV spread requires approaches that target early stages of infection, i.e., virus entry. However, little is known about the molecular and cellular mechanisms by which OBVs enter and infect host cells. Here, we developed accurate, sensitive tools and assays to investigate the penetration process of GERV. Our data emphasize the central role of late endosomal maturation in GERV entry, providing a comprehensive overview of the early stages of an OBV infection. Our study also brings a complete toolbox of innovative methods to study each step of the OBV entry program in fixed and living cells, from virus binding and endocytosis to fusion and penetration. The information gained herein lays the foundation for the development of antiviral strategies aiming to block OBV entry.
Topics: Animals; Cryoelectron Microscopy; Endosomes; Mammals; Orthobunyavirus; Virus Internalization
PubMed: 35019710
DOI: 10.1128/jvi.02146-21 -
The American Journal of Tropical... May 2017AbstractOropouche virus (OROV) is an important cause of arboviral illness in Latin American countries, more specifically in the Amazon region of Brazil, Venezuela and... (Review)
Review
AbstractOropouche virus (OROV) is an important cause of arboviral illness in Latin American countries, more specifically in the Amazon region of Brazil, Venezuela and Peru, as well as in other countries such as Panama. In the past decades, the clinical, epidemiological, pathological, and molecular aspects of OROV have been published and provide the basis for a better understanding of this important human pathogen. Here, we describe the milestones in a comprehensive review of OROV epidemiology, pathogenesis, and molecular biology, including a description of the first isolation of the virus, the outbreaks during the past six decades, clinical aspects of OROV infection, diagnostic methods, genome and genetic traits, evolution, and viral dispersal.
Topics: Animals; Birds; Brazil; Bunyaviridae Infections; Ceratopogonidae; Chromosome Mapping; Culex; Disease Outbreaks; Disease Vectors; Genome, Viral; Genotype; Humans; Orthobunyavirus; Panama; Peru; Sloths; Venezuela
PubMed: 28167595
DOI: 10.4269/ajtmh.16-0672 -
The Veterinary Record Aug 2014British sheep farmers were invited to complete a questionnaire about the impact of Schmallenberg virus (SBV) on animal health, welfare and their own emotional wellbeing...
British sheep farmers were invited to complete a questionnaire about the impact of Schmallenberg virus (SBV) on animal health, welfare and their own emotional wellbeing during the 2011-2012 lambing season, through Defra and Farming Industry websites, letters to farmers who had requested SBV laboratory tests and advertisement at Sheep 2012. The 494 responders included SBV confirmed (positive by RT-PCR) (n=76), SBV suspected by farmer (n=140) or SBV not suspected (n=278). Percentage of barren ewes was similar across SBV groups, however, lamb and ewe losses were higher on responder farms where SBV was confirmed or suspected. The median percentages of all lambs born (and lambs born deformed ) that died within one week of birth was 10.4 per cent (5.5 per cent), 7.0 per cent (2.9 per cent) and 5.3 per cent (0 per cent), respectively, on SBV confirmed, suspected and not suspected farms (P<0.001). Eight to 16 per cent of SBV confirmed or suspected farms reported lamb mortality of ≥40 per cent. Farmer perceived impact was greater where SBV was confirmed or suspected (P<0.001): 25 per cent reported a high impact on emotional wellbeing (4 per cent of SBV not suspected), 13 per cent reported a high impact on flock welfare and financial performance and 6 per cent were less likely to farm sheep next year because of SBV (<2 per cent in SBV not suspected). Overall, SBV impact has been large relative to reported sheep loss.
Topics: Agriculture; Animals; Bunyaviridae Infections; Cost of Illness; Female; Orthobunyavirus; Pregnancy; Seasons; Sheep; Sheep Diseases; United Kingdom
PubMed: 24795165
DOI: 10.1136/vr.102295 -
Oncotarget Dec 2015
Topics: Animals; Arenaviridae; Filoviridae; Flaviviridae; Hemorrhagic Fevers, Viral; Host-Pathogen Interactions; Humans; Immune Tolerance; Immunity, Innate; Orthobunyavirus; Signal Transduction
PubMed: 26657729
DOI: 10.18632/oncotarget.6509 -
Epidemiology and Infection Jan 2013In 2011, a novel orthobunyavirus of the Simbu serogroup, the Schmallenberg virus (SBV), was discovered using a metagenomic approach. SBV caused a large epidemic in... (Review)
Review
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.
Topics: Animal Diseases; Animals; Bunyaviridae Infections; Ceratopogonidae; Communicable Diseases, Emerging; Disease Vectors; Europe; Orthobunyavirus; Ruminants; Seroepidemiologic Studies
PubMed: 23046921
DOI: 10.1017/S0950268812002245 -
Proceedings of the National Academy of... Aug 2016The M genome segment of Bunyamwera virus (BUNV)-the prototype of both the Bunyaviridae family and the Orthobunyavirus genus-encodes the glycoprotein precursor (GPC) that...
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 SP(NSm) and NSm domain V as SP(Gc) 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 (SP(Gc)) 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.
Topics: A549 Cells; Animals; Aspartic Acid Endopeptidases; Binding Sites; Bunyamwera virus; Cell Line; Cell Line, Tumor; Chlorocebus aethiops; Glycoproteins; HEK293 Cells; Host-Pathogen Interactions; Humans; Membrane Proteins; Protein Precursors; Proteolysis; Serine Endopeptidases; Vero Cells; Viral Nonstructural Proteins
PubMed: 27439867
DOI: 10.1073/pnas.1603364113 -
Viruses Nov 2019First appearing in 2011 in Northern Europe, Schmallenberg virus (SBV), an of the Simbu serogroup, is associated with clinical disease mainly in ruminants such as... (Review)
Review
First appearing in 2011 in Northern Europe, Schmallenberg virus (SBV), an of the Simbu serogroup, is associated with clinical disease mainly in ruminants such as cattle, sheep and goats. The clinical signs are characterized by abortion and congenital deformities in newborns. The virus is transmitted by Culicoides midges of the Obsoletus complex. SBV infection induces a solid protective immunity that persists for at least 4 or 6 years in sheep and cattle, respectively. SBV infection can be diagnosed directly by real-time RT-qPCR and virus isolation or indirectly by serological assays. Three vaccines are commercially available in Europe. This article provides a comprehensive literature review on this emerging disease regarding pathogenesis, transmission, diagnosis, control and prevention. This review also highlights that although much has been learned since SBV's first emergence, there are still areas that require further study to devise better mitigation strategies.
Topics: Animal Diseases; Animals; Bunyaviridae Infections; Ceratopogonidae; Communicable Disease Control; Communicable Diseases, Emerging; Disease Susceptibility; Genome, Viral; Genomics; Insect Vectors; Orthobunyavirus; Public Health Surveillance; Ruminants; Viral Vaccines
PubMed: 31731618
DOI: 10.3390/v11111065 -
Veterinary Research May 2013After the unexpected emergence of Bluetongue virus serotype 8 (BTV-8) in northern Europe in 2006, another arbovirus, Schmallenberg virus (SBV), emerged in Europe in 2011... (Review)
Review
After the unexpected emergence of Bluetongue virus serotype 8 (BTV-8) in northern Europe in 2006, another arbovirus, Schmallenberg virus (SBV), emerged in Europe in 2011 causing a new economically important disease in ruminants. The virus, belonging to the Orthobunyavirus genus in the Bunyaviridae family, was first detected in Germany, in The Netherlands and in Belgium in 2011 and soon after in the United Kingdom, France, Italy, Luxembourg, Spain, Denmark and Switzerland. This review describes the current knowledge on the emergence, epidemiology, clinical signs, molecular virology and diagnosis of SBV infection.
Topics: Animals; Bunyaviridae Infections; Communicable Diseases, Emerging; Europe; Orthobunyavirus; Ruminants
PubMed: 23675914
DOI: 10.1186/1297-9716-44-31 -
Emerging Infectious Diseases 2021We describe an Oropouche orthobunyavirus infection in a women 28 years of age in Colombia. We confirmed the diagnosis by viral isolation, quantitative reverse...
We describe an Oropouche orthobunyavirus infection in a women 28 years of age in Colombia. We confirmed the diagnosis by viral isolation, quantitative reverse transcription PCR, and phylogenetic analysis of the small, medium, and large genomic segments. The virus is related to a strain isolated in Ecuador in 2016.
Topics: Bunyaviridae Infections; Colombia; Ecuador; Female; Humans; Orthobunyavirus; Phylogeny; RNA, Viral
PubMed: 34014154
DOI: 10.3201/eid2706.204405 -
Veterinary Journal (London, England :... Oct 2012The large-scale outbreak of disease across Northern Europe caused by a new orthobunyavirus known as Schmallenberg virus has caused considerable disruption to lambing and... (Review)
Review
The large-scale outbreak of disease across Northern Europe caused by a new orthobunyavirus known as Schmallenberg virus has caused considerable disruption to lambing and calving. Although advances in technology and collaboration between veterinary diagnostic and research institutes have enabled rapid identification of the causative agent and the development and deployment of tests, much remains unknown about this virus and its epidemiology that make predictions of its future impact difficult to assess. This review outlines current knowledge of the virus, drawing comparisons with related viruses, then explores possible scenarios of its impact in the near future, and highlights some of the urgent research questions that need to be addressed to allow the development of appropriate control strategies.
Topics: Animals; Bunyaviridae Infections; Disease Outbreaks; Europe; Orthobunyavirus
PubMed: 23026716
DOI: 10.1016/j.tvjl.2012.08.017