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Viruses Jul 2021Statin derivatives can inhibit the replication of a range of viruses, including hepatitis C virus (HCV, ), dengue virus (), African swine fever virus () and poliovirus...
Statin derivatives can inhibit the replication of a range of viruses, including hepatitis C virus (HCV, ), dengue virus (), African swine fever virus () and poliovirus (). We assess the antiviral effect of fluvastatin in cells infected with orbiviruses (bluetongue virus (BTV) and Great Island virus (GIV)). The synthesis of orbivirus outer-capsid protein VP2 (detected by confocal immunofluorescence imaging) was used to assess levels of virus replication, showing a reduction in fluvastatin-treated cells. A reduction in virus titres of ~1.7 log (98%) in fluvastatin-treated cells was detected by a plaque assay. We have previously identified a fourth non-structural protein (NS4) of BTV and GIV, showing that it interacts with lipid droplets in infected cells. Fluvastatin, which inhibits 3-hydroxy 3-methyl glutaryl CoA reductase in the mevalonic acid pathway, disrupts these NS4 interactions. These findings highlight the role of the lipid pathways in orbivirus replication and suggest a greater role for the membrane-enveloped orbivirus particles than previously recognised. Chemical intermediates of the mevalonic acid pathway were used to assess their potential to rescue orbivirus replication. Pre-treatment of IFNAR mice with fluvastatin promoted their survival upon challenge with live BTV, although only limited protection was observed.
Topics: Animals; Antiviral Agents; Bluetongue; Bluetongue virus; Cell Line; Ceratopogonidae; Fluvastatin; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Metabolic Networks and Pathways; Mevalonic Acid; Mice; Orbivirus; Receptor, Interferon alpha-beta; Viral Load; Virus Replication; Yellow fever virus
PubMed: 34452303
DOI: 10.3390/v13081437 -
Virus Research Sep 2021Ibaraki virus (IBAV) is the pathogen associated with Ibaraki disease. In a previous study, we suggested that IBAV enters hamster lung (HmLu-1) cells via endocytosis and...
Ibaraki virus (IBAV) is the pathogen associated with Ibaraki disease. In a previous study, we suggested that IBAV enters hamster lung (HmLu-1) cells via endocytosis and subsequently escapes into the cytoplasm upon endosomal acidification. However, it is unclear which of the endocytic pathways IBAV utilizes. In this study, we aimed to further elucidate the pathway of IBAV entry into host cells. We found that IBAV replication was not suppressed by inhibitors of clathrin-mediated or caveolin-mediated endocytosis but was markedly suppressed by 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and cytochalasin D, both of which inhibit macropinocytosis. Monensin, which inhibits endosomal acidification, also suppressed IBAV replication. To assess the inhibitory effects of these reagents on endocytosis, dextran and transferrin were used as indicators of macropinocytosis and clathrin-mediated endocytic activity, respectively. Our data confirmed that EIPA and monensin inhibited dextran uptake, and cytochalasin D inhibited the uptake of both. Additionally, we confirmed that endosomal/lysosomal acidification was inhibited by monensin. These results suggest that the macropinocytosis pathway is the major route of IBAV entry and confirm that IBAV infection of HmLu-1 cells is dependent on endosomal acidification.
Topics: Animals; Cell Line; Clathrin; Cricetinae; Cytochalasin D; Dextrans; Endocytosis; Monensin; Orbivirus; Pinocytosis; Virus Internalization
PubMed: 34174342
DOI: 10.1016/j.virusres.2021.198492 -
Viruses May 2022Tick-borne viruses are responsible for various symptoms in humans and animals, ranging from simple fever to neurological disorders or haemorrhagic fevers. The Kemerovo...
Tick-borne viruses are responsible for various symptoms in humans and animals, ranging from simple fever to neurological disorders or haemorrhagic fevers. The Kemerovo virus (KEMV) is a tick-borne orbivirus, and it has been suspected to be responsible for human encephalitis cases in Russia and central Europe. It has been isolated from and ticks. In a previous study, we assessed the vector competence of larvae from Slovakia for KEMV, using an artificial feeding system. In the current study, we used the same system to infect different tick population/species, including larvae from France and nymphs from Slovakia, and larvae from Russia. We successfully confirmed the first two criteria of vector competence, namely, virus acquisition and trans-stadial transmission, for both tick species that we tested. The estimated infection rates of engorged and moulted ticks suggest specificities between viral strains and tick species/developmental stages.
Topics: Animals; Disease Vectors; Europe; Ixodes; Larva; Orbivirus
PubMed: 35632845
DOI: 10.3390/v14051102 -
Viruses Sep 2019African horse sickness is a devastating disease that causes great suffering and many fatalities amongst horses in sub-Saharan Africa. It is caused by nine different... (Review)
Review
African horse sickness is a devastating disease that causes great suffering and many fatalities amongst horses in sub-Saharan Africa. It is caused by nine different serotypes of the orbivirus African horse sickness virus (AHSV) and it is spread by Culicoid midges. The disease has significant economic consequences for the equine industry both in southern Africa and increasingly further afield as the geographic distribution of the midge vector broadens with global warming and climate change. Live attenuated vaccines (LAV) have been used with relative success for many decades but carry the risk of reversion to virulence and/or genetic re-assortment between outbreak and vaccine strains. Furthermore, the vaccines lack DIVA capacity, the ability to distinguish between vaccine-induced immunity and that induced by natural infection. These concerns have motivated interest in the development of new, more favourable recombinant vaccines that utilize viral vectors or are based on reverse genetics or virus-like particle technologies. This review summarizes the current understanding of AHSV structure and the viral replication cycle and also evaluates existing and potential vaccine strategies that may be applied to prevent or control the disease.
Topics: Africa, Southern; African Horse Sickness; African Horse Sickness Virus; Animals; Antibodies, Neutralizing; Antibodies, Viral; Ceratopogonidae; Horses; Reverse Genetics; Vaccines, Attenuated; Vaccines, Synthetic; Viral Vaccines
PubMed: 31514299
DOI: 10.3390/v11090844 -
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 -
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 -
Transboundary and Emerging Diseases Jan 2020Bluetongue virus (Reoviridae; Orbivirus, BTV), which is usually transmitted by biting midges, affects wild and domestic ruminants worldwide, thereby causing an...
Bluetongue virus (Reoviridae; Orbivirus, BTV), which is usually transmitted by biting midges, affects wild and domestic ruminants worldwide, thereby causing an economically important disease. Recently, a putative new BTV strain was isolated from contaminated vaccine batches. In this study, we investigated the genomic and clinical characteristics of this isolate, provisionally designated BTV-28. Phylogenetic analysis of BTV-28 segment 2 (Seg-2) showed that it is related to Seg-2 from BTV serotypes 4, 10, 11, 17, 20 and 24, sharing 64%-66% identity in nucleotide sequences (nt) and 59%-62% in amino acid (aa) sequences of BTV VP2. BTV-28 Seg-6 is related to the newly reported XJ1407 BTV isolate, sharing 76.70% nt and 90.87% aa sequence identity. Seg-5 was most closely related to a South African BTV-4 strain, and all other segments showed close similarity to BTV-26. Experimental infection by injection of 6-month-old ewes caused clinical signs in all injected animals, lasting from 2 to 3 days to several weeks post-infection, including high body temperature, conjunctivitis, nasal discharge and rhinitis, facial oedema, oral hyperaemia, coronitis, cough, depression and tongue cyanosis. Naïve control animals, placed together with the infected sheep, displayed clinical signs and were positive for viral RNA, but their acute disease phase was shorter than that of BTV-injected ewes. Control animals that were kept in a separated pen did not display any clinical signs and were negative for viral RNA presence throughout the experiment. Seroconversion was observed in the injected and in one of the two contact-infected animals. These findings demonstrate that BTV-28 infection of sheep can result in clinical manifestation, and the clinical signs detected in the contact animals suggest that it might be directly transmitted between the mammalian hosts.
Topics: Animals; Bluetongue; Bluetongue virus; Capripoxvirus; Ceratopogonidae; Female; Phylogeny; Poxviridae Infections; RNA, Viral; Serogroup; Sheep; Sheep Diseases; Viral Vaccines
PubMed: 31469936
DOI: 10.1111/tbed.13338 -
Viruses May 2022is a family of viruses belonging to the order and comprises six genera, two of which, and , contain arboviruses that cause disease in humans and livestock. Areas such...
is a family of viruses belonging to the order and comprises six genera, two of which, and , contain arboviruses that cause disease in humans and livestock. Areas such as Yunnan Province in southwestern China, have high arboviral activity due in part to warm and wet summers, which support high populations of biting flies such as mosquitoes and . Three viral isolates previously obtained from collected at cattle farms in Shizong County of Yunnan Province, China, between 2019 and 2020 were completely sequenced and identified as Banna virus (BAV) genotype A of and serotypes 1 and 7 of epizootic hemorrhagic disease virus (EHDV) of . These results suggest that and are potential vectors of BAV and EHDV, respectively, and represent the first association of a BAV with and of an arbovirus with . Analysis using VP9 generally agreed with the current groupings within this genus based on VP12, although the classification for some strains should be corrected. Furthermore, the placement of Kadipiro virus (KDV) and Liao ning virus (LNV) in may need confirmation as phylogenetic analysis placed these viruses as sister to other species in the genus.
Topics: Animals; Arboviruses; Cattle; Ceratopogonidae; China; Coltivirus; Hemorrhagic Disease Virus, Epizootic; Mosquito Vectors; Phylogeny; Reoviridae
PubMed: 35632713
DOI: 10.3390/v14050971 -
Viruses Apr 2015The International Committee for Taxonomy of Viruses (ICTV) recognizes four species of tick-borne orbiviruses (TBOs): Chenuda virus, Chobar Gorge virus, Wad Medani virus...
The International Committee for Taxonomy of Viruses (ICTV) recognizes four species of tick-borne orbiviruses (TBOs): Chenuda virus, Chobar Gorge virus, Wad Medani virus and Great Island virus (genus Orbivirus, family Reoviridae). Nucleotide (nt) and amino acid (aa) sequence comparisons provide a basis for orbivirus detection and classification, however full genome sequence data were only available for the Great Island virus species. We report representative genome-sequences for the three other TBO species (virus isolates: Chenuda virus (CNUV); Chobar Gorge virus (CGV) and Wad Medani virus (WMV)). Phylogenetic comparisons show that TBOs cluster separately from insect-borne orbiviruses (IBOs). CNUV, CGV, WMV and GIV share low level aa/nt identities with other orbiviruses, in 'conserved' Pol, T2 and T13 proteins/genes, identifying them as four distinct virus-species. The TBO genome segment encoding cell attachment, outer capsid protein 1 (OC1), is approximately half the size of the equivalent segment from insect-borne orbiviruses, helping to explain why tick-borne orbiviruses have a ~1 kb smaller genome.
Topics: Animals; Cluster Analysis; Genome, Viral; Molecular Sequence Data; Orbivirus; Phylogeny; RNA, Viral; Sequence Analysis, DNA; Sequence Homology; Ticks
PubMed: 25928203
DOI: 10.3390/v7052185 -
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