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Virology Feb 1996Orbiviruses (Reoviridae family) are complex nonenveloped RNA viruses with seven structural proteins and a RNA genome consisting of 10 variously sized double-stranded RNA... (Review)
Review
Orbiviruses (Reoviridae family) are complex nonenveloped RNA viruses with seven structural proteins and a RNA genome consisting of 10 variously sized double-stranded RNA segments. Significant advances in orbivirus research have been made in recent years through the use of gene manipulation techniques coupled with the baculovirus expression system. Several orbivirus proteins have yielded to crystallization and X-ray crystallographic structure determination and, when combined with the three-dimensional image reconstruction of virion particles and cores obtained by cryoelectron microscopy, considerable insight has been gained into the intricate organization and topography of the individual viral components. Formal identification of the sites of interaction has been obtained through protein-protein interaction studies on the components of the virion particle, including those that are involved in capsid assembly. Finally, a beginning of the understanding of the sequence of assembly events has also been obtained.
Topics: Animals; Bluetongue virus; Orbivirus; Viral Proteins; Virus Assembly
PubMed: 8614976
DOI: 10.1006/viro.1996.0028 -
Viruses Sep 2023Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein...
Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or African horse sickness virus. We further explored the functional role(s) of NS4 proteins of BTV and the tick-borne Great Island virus (GIV). We show that NS4 of BTV or GIV helps an E3L deletion mutant of vaccinia virus to replicate efficiently in interferon-treated cells, further confirming the role of NS4 as an interferon antagonist. Our results indicate that ectopically expressed NS4 of BTV localised with caspase 3 within the nucleus and was found in a protein complex with active caspase 3 in a pull-down assay. Previous studies have shown that pro-apoptotic caspases (including caspase 3) suppress type I interferon response by cleaving mediators involved in interferon signalling. Our data suggest that orbivirus NS4 plays a role in modulating the apoptotic process and/or regulating the interferon response in mammalian cells, thus acting as a virulence factor in pathogenesis.
Topics: Animals; Orbivirus; Caspase 3; Bluetongue virus; Apoptosis; Interferon Type I; Thogotovirus; Mammals
PubMed: 37766314
DOI: 10.3390/v15091908 -
Viruses Sep 2021Understanding how viruses with multi-segmented genomes incorporate one copy of each segment into their capsids remains an intriguing question. Here, we review our recent... (Review)
Review
Understanding how viruses with multi-segmented genomes incorporate one copy of each segment into their capsids remains an intriguing question. Here, we review our recent progress and describe the advancements made in understanding the genome packaging mechanism of a model nonenveloped virus, Bluetongue virus (BTV), with a 10-segment (S1-S10) double-strand RNA (dsRNA) genome. BTV (multiple serotypes), a member of the genus in the family, is a notable pathogen for livestock and is responsible for significant economic losses worldwide. This has enabled the creation of an extensive set of reagents and assays, including reverse genetics, cell-free RNA packaging, and bespoke bioinformatics approaches, which can be directed to address the packaging question. Our studies have shown that (i) UTRs enable the conformation of each segment necessary for the next level of RNA-RNA interaction; (ii) a specific order of intersegment interactions leads to a complex RNA network containing all the active components in sorting and packaging; (iii) networked segments are recruited into nascent assembling capsids; and (iv) select capsid proteins might be involved in the packaging process. The key features of genome packaging mechanisms for BTV and related dsRNA viruses are novel and open up new avenues of potential intervention.
Topics: Animals; Bluetongue virus; Capsid Proteins; Genome, Viral; Nucleic Acid Conformation; RNA, Double-Stranded; RNA, Viral; Viral Genome Packaging; Viral Nonstructural Proteins; Virus Assembly; Virus Replication
PubMed: 34578422
DOI: 10.3390/v13091841 -
Journal of Medical Entomology Nov 2023Orbiviruses are of significant importance to the health of wildlife and domestic animals worldwide; the major orbiviruses transmitted by multiple biting midge...
Orbiviruses are of significant importance to the health of wildlife and domestic animals worldwide; the major orbiviruses transmitted by multiple biting midge (Culicoides) species include bluetongue virus, epizootic hemorrhagic disease virus, and African horse sickness virus. The viruses, insect vectors, and hosts are anticipated to be impacted by global climate change, altering established Orbivirus epidemiology. Changes in global climate have the potential to alter the vector competence and extrinsic incubation period of certain biting midge species, affect local and long-distance dispersal dynamics, lead to range expansion in the geographic distribution of vector species, and increase transmission period duration (earlier spring onset and later fall transmission). If transmission intensity is associated with weather anomalies such as droughts and wind speeds, there may be changes in the number of outbreaks and periods between outbreaks for some regions. Warmer temperatures and changing climates may impact the viral genome by facilitating reassortment and through the emergence of novel viral mutations. As the climate changes, Orbivirus epidemiology will be inextricably altered as has been seen with recent outbreaks of bluetongue, epizootic hemorrhagic disease, and African horse sickness outside of endemic areas, and requires interdisciplinary teams and approaches to assess and mitigate future outbreak threats.
Topics: Horses; Animals; Orbivirus; Ceratopogonidae; African Horse Sickness Virus; African Horse Sickness; Climate Change; Horse Diseases
PubMed: 37862060
DOI: 10.1093/jme/tjad098 -
EcoHealth Dec 2022Orbiviruses are arthropod borne viruses of vertebrates, with some of them being important pathogens of veterinary, conservation and economic importance, while others are...
Orbiviruses are arthropod borne viruses of vertebrates, with some of them being important pathogens of veterinary, conservation and economic importance, while others are occasionally associated with human disease. Some apparently bat specific orbiviruses have been detected, but little is known about their distribution and diversity. We thus sampled and screened 52 bats living in the Congo Basin, and detected RNA indicative of a novel orbivirus in a single banana serotine (Afronycteris nanus) by PCR. The detected RNA clusters with epizootic haemorrhagic disease virus, bluetongue virus, and others. The findings highlight the need for more studies into arbovirus presence and diversity in bat species.
Topics: Animals; Humans; Orbivirus; Chiroptera; Congo; Musa; RNA; Arboviruses
PubMed: 36629956
DOI: 10.1007/s10393-022-01619-2 -
International Journal of Molecular... Oct 2020Bluetongue virus (BTV) and African horse sickness virus (AHSV) are vector-borne viruses belonging to the genus, which are transmitted between hosts primarily by biting...
Bluetongue virus (BTV) and African horse sickness virus (AHSV) are vector-borne viruses belonging to the genus, which are transmitted between hosts primarily by biting midges of the genus . With recent BTV and AHSV outbreaks causing epidemics and important economy losses, there is a pressing need for efficacious drugs to treat and control the spread of these infections. The polyanionic aromatic compound aurintricarboxylic acid (ATA) has been shown to have a broad-spectrum antiviral activity. Here, we evaluated ATA as a potential antiviral compound against infections in both mammalian and insect cells. Notably, ATA was able to prevent the replication of BTV and AHSV in both cell types in a time- and concentration-dependent manner. In addition, we evaluated the effect of ATA in vivo using a mouse model of infection. ATA did not protect mice against a lethal challenge with BTV or AHSV, most probably due to the in vivo effect of ATA on immune system regulation. Overall, these results demonstrate that ATA has inhibitory activity against replication in vitro, but further in vivo analysis will be required before considering it as a potential therapy for future clinical evaluation.
Topics: African Horse Sickness; African Horse Sickness Virus; Animals; Aurintricarboxylic Acid; Bluetongue virus; Ceratopogonidae; Horses; Sheep; Virus Diseases; Virus Replication
PubMed: 33023235
DOI: 10.3390/ijms21197294 -
Current Opinion in Virology Oct 2020Bluetongue virus (BTV) reverse genetics (RG), available since 2007, has allowed the dissection of the virus replication cycle, including discovery of a primary... (Review)
Review
Bluetongue virus (BTV) reverse genetics (RG), available since 2007, has allowed the dissection of the virus replication cycle, including discovery of a primary replication stage. This information has allowed the generation of Entry-Competent-Replication-Abortive (ECRA) vaccines, which enter cells and complete primary replication but fail to complete the later stage. A series of vaccine trials in sheep and cattle either with a single ECRA serotype or a cocktail of multiple ECRA serotypes have demonstrated that these vaccines provide complete protection against virulent virus challenge without cross-serotype interference. Similarly, an RG system developed for the related African Horse Sickness virus, which causes high mortality in equids has provided AHSV ECRA vaccines that are protective in horses. ECRA vaccines were incapable of productive replication in animals despite being competent for cell entry. This technology allows rapid generation of emerging Orbivirus vaccines and offers immunogenicity and safety levels that surpass attenuated or recombinant routes.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Bluetongue; Bluetongue virus; Cattle; Orbivirus; Reoviridae Infections; Reverse Genetics; Sheep; Vaccines, Attenuated; Viral Vaccines; Virus Replication
PubMed: 32610251
DOI: 10.1016/j.coviro.2020.05.003 -
Vector Borne and Zoonotic Diseases... Jun 2015Although recognized as causing emerging and re-emerging disease outbreaks worldwide since the late 1800 s, there has been growing interest in the United States and... (Review)
Review
Although recognized as causing emerging and re-emerging disease outbreaks worldwide since the late 1800 s, there has been growing interest in the United States and Europe in recent years in orbiviruses, their insect vectors, and the diseases they cause in domestic livestock and wildlife. This is due, in part, to the emergence of bluetongue (BT) in northern Europe in 2006-2007 resulting in a devastating outbreak, as well as severe BT outbreaks in sheep and epizootic hemorrhagic disease (EHD) outbreaks in deer and cattle in the United States. Of notable concern is the isolation of as many as 10 new BT virus (BTV) serotypes in the United States since 1999 and their associated unknowns, such as route of introduction, virulence to mammals, and indigenous competent vectors. This review, based on a gap analysis workshop composed of international experts on orbiviruses conducted in 2013, gives a global perspective of current basic virological understanding of orbiviruses, with particular attention to BTV and the closely related epizootic hemorrhagic disease virus (EHDV), and identifies a multitude of basic virology research gaps, critical for predicting and preventing outbreaks.
Topics: Animals; Bluetongue; Bluetongue virus; Disease Outbreaks; Hemorrhagic Disease Virus, Epizootic; Host Specificity; Insect Vectors; Orbivirus; Reoviridae Infections; Research; Sheep
PubMed: 26086555
DOI: 10.1089/vbz.2014.1701 -
Current Topics in Microbiology and... 2006X-ray and electron microscopy analysis of Bluetongue virus (BTV), the type species of the Orbivirus genus within the family Reoviridae, have revealed various aspects of... (Review)
Review
X-ray and electron microscopy analysis of Bluetongue virus (BTV), the type species of the Orbivirus genus within the family Reoviridae, have revealed various aspects of the organisation and structure of the proteins that form the viral capsid. Orbiviruses have a segmented dsRNA genome, which imposes constraints on their structure and life cycle. The atomic structure of the BTV core particle, the key viral component which transcribes the viral mRNA within the cell cytoplasm, revealed the architecture and assembly of the major core proteins VP7 and VP3. In addition, these studies formed the basis for a plausible model for the organisation of the dsRNA viral genome and the arrangement of the viral transcriptase complex (composed of the RNA-dependent RNA polymerase, the viral capping enzyme and RNA helicase) that resides within the core particle. Electron cryo-microscopy of the viral particle has shown how the two viral proteins VP2 and VP5 are arranged to form the outer capsid, with distinct packing arrangements between them and the core protein VP7. By comparison of the outer capsid proteins of orbiviruses with those of other nonturreted members of the family Reoviridae, we are able to propose a more detailed model of these structures and possible mechanisms for cell entry. Further structural results are also discussed including the atomic structure of an N-terminal domain of nonstructural protein NS2, a protein involved in virus genome assembly and morphogenesis.
Topics: Biological Transport; Capsid Proteins; Genome, Viral; Orbivirus; Transcription, Genetic; Viral Core Proteins; Viral Nonstructural Proteins; Viral Proteins; Virion
PubMed: 16909901
DOI: 10.1007/3-540-30773-7_8 -
Current Opinion in Virology Dec 2017Congenital infections of domestic animals with viruses in several families, including Bunyaviridae, Flaviridae, Parvoviridae, and Reoviridae, are the cause of naturally... (Review)
Review
Congenital infections of domestic animals with viruses in several families, including Bunyaviridae, Flaviridae, Parvoviridae, and Reoviridae, are the cause of naturally occurring teratogenic central nervous system and/or musculoskeletal defects (arthrogryposis) in domestic animals. Congenital infections of ruminant livestock with bluetongue virus (BTV) and some related members of the genus Orbivirus (family Reoviridae) have clearly shown the critical role of gestational age at infection in determining outcome. Specifically, fetuses infected prior to mid-gestation that survive congenital BTV infection are born with cavitating central nervous system defects that range from severe hydranencephaly to cerebral cysts (porencephaly). Generally, the younger the fetus (in terms of gestational age) at infection, the more severe the teratogenic lesion at birth. Age-dependent virus infection and destruction of neuronal and/or glial cell precursors that populate the developing central nervous system are responsible for these naturally occurring virus-induced congenital defects of animals, thus lesions are most severe when progenitor cells are infected prior to their normal migration during embryogenesis. Whereas congenital infection is characteristic of certain BTV strains, notably live-attenuated (modified-live) vaccine viruses that have been passaged in embryonating eggs, transplacental transmission is not characteristic of many field strains of the virus and much remains to be determined regarding the genetic determinants of transplacental transmission of individual virus strains.
Topics: Age Factors; Animals; Bluetongue; Bluetongue virus; Congenital Abnormalities; Female; Gestational Age; Infectious Disease Transmission, Vertical; Livestock; Orbivirus; Pregnancy; Reoviridae Infections; Ruminants; Sheep; Teratogens; Virus Diseases
PubMed: 29107849
DOI: 10.1016/j.coviro.2017.10.002