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16 pages, 3563 KiB

Open AccessArticle

Comparative Virus-Host Protein Interactions of the Bluetongue Virus NS4 Virulence Factor

by Aurore Fablet, Cindy Kundlacz, Juliette Dupré, Edouard Hirchaud, Lydie Postic, Corinne Sailleau, Emmanuel Bréard, Stéphan Zientara, Damien Vitour and Grégory Caignard

Viruses 2022, 14(2), 182; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020182 - 19 Jan 2022

Cited by 2 | Viewed by 1874

Abstract

Bluetongue virus (BTV) is the etiologic agent of a non-contagious arthropod-borne disease transmitted to wild and domestic ruminants. BTV induces a large panel of clinical manifestations ranging from asymptomatic infection to lethal hemorrhagic fever. Despite the fact that BTV has been studied extensively, [...] Read more.

Bluetongue virus (BTV) is the etiologic agent of a non-contagious arthropod-borne disease transmitted to wild and domestic ruminants. BTV induces a large panel of clinical manifestations ranging from asymptomatic infection to lethal hemorrhagic fever. Despite the fact that BTV has been studied extensively, we still have little understanding of the molecular determinants of BTV virulence. In our report, we have performed a comparative yeast two-hybrid (Y2H) screening approach to search direct cellular targets of the NS4 virulence factor encoded by two different serotypes of BTV: BTV8 and BTV27. This led to identifying Wilms’ tumor 1-associated protein (WTAP) as a new interactor of the BTV-NS4. In contrast to BTV8, 1, 4 and 25, NS4 proteins from BTV27 and BTV30 are unable to interact with WTAP. This interaction with WTAP is carried by a peptide of 34 amino acids (NS4²²⁻⁵⁵) within its putative coil-coiled structure. Most importantly, we showed that binding to WTAP is restored with a chimeric protein where BTV27-NS4 is substituted by BTV8-NS4 in the region encompassing residue 22 to 55. We also demonstrated that WTAP silencing reduces viral titers and the expression of viral proteins, suggesting that BTV-NS4 targets a cellular function of WTAP to increase its viral replication. Full article

(This article belongs to the Special Issue Bluetongue Virus (BTV))

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17 pages, 17811 KiB

Open AccessArticle

Putative Novel Atypical BTV Serotype ‘36’ Identified in Small Ruminants in Switzerland

by Christina Ries, Andrea Vögtlin, Daniela Hüssy, Tabea Jandt, Hansjörg Gobet, Monika Hilbe, Carole Burgener, Luzia Schweizer, Stephanie Häfliger-Speiser, Martin Beer and Bernd Hoffmann

Viruses 2021, 13(5), 721; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050721 - 21 Apr 2021

Cited by 30 | Viewed by 2466

Abstract

We identified a putative novel atypical BTV serotype ‘36’ in Swiss goat flocks. In the initial flock clinical signs consisting of multifocal purulent dermatitis, facial oedema and fever were observed. Following BTV detection by RT-qPCR, serotyping identified BTV-25 and also a putative novel [...] Read more.

We identified a putative novel atypical BTV serotype ‘36’ in Swiss goat flocks. In the initial flock clinical signs consisting of multifocal purulent dermatitis, facial oedema and fever were observed. Following BTV detection by RT-qPCR, serotyping identified BTV-25 and also a putative novel BTV serotype in several of the affected goats. We successfully propagated the so-called “BTV-36-CH2019” strain in cell culture, developed a specific RT-qPCR targeting Segment 2, and generated the full genome by high-throughput sequencing. Furthermore, we experimentally infected goats with BTV-36-CH2019. Regularly, EDTA blood, serum and diverse swab samples were collected. Throughout the experiment, neither fever nor clinical disease was observed in any of the inoculated goats. Four goats developed BTV viremia, whereas one inoculated goat and the two contact animals remained negative. No viral RNA was detected in the swab samples collected from nose, mouth, eye, and rectum, and thus the experimental infection of goats using this novel BTV serotype delivered no indications for any clinical symptoms or vector-free virus transmission pathways. The subclinical infection of the four goats is in accordance with the reports for other atypical BTVs. However, the clinical signs of the initial goat flock did most likely not result from infection with the novel BTV-36-CH0219. Full article

(This article belongs to the Special Issue Bluetongue Virus (BTV))

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16 pages, 901 KiB

Open AccessArticle

Transmission of Bluetongue Virus Serotype 8 by Artificial Insemination with Frozen–Thawed Semen from Naturally Infected Bulls

by Kris De Clercq, Leen Vandaele, Tine Vanbinst, Mickaël Riou, Isra Deblauwe, Wendy Wesselingh, Anne Pinard, Mieke Van Eetvelde, Olivier Boulesteix, Bart Leemans, Robert Gélineau, Griet Vercauteren, Sara Van der Heyden, Jean-François Beckers, Claude Saegerman, Donal Sammin, Aart de Kruif and Ilse De Leeuw

Viruses 2021, 13(4), 652; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040652 - 09 Apr 2021

Cited by 8 | Viewed by 2706

Abstract

Transmission of bluetongue (BT) virus serotype 8 (BTV-8) via artificial insemination of contaminated frozen semen from naturally infected bulls was investigated in two independent experiments. Healthy, BT negative heifers were hormonally synchronized and artificially inseminated at oestrus. In total, six groups of three [...] Read more.

Transmission of bluetongue (BT) virus serotype 8 (BTV-8) via artificial insemination of contaminated frozen semen from naturally infected bulls was investigated in two independent experiments. Healthy, BT negative heifers were hormonally synchronized and artificially inseminated at oestrus. In total, six groups of three heifers received semen from four batches derived from three bulls naturally infected with BTV-8. Each experiment included one control heifer that was not inseminated and that remained BT negative throughout. BTV viraemia and seroconversion were determined in 8 out of 18 inseminated heifers, and BTV was isolated from five of these animals. These eight heifers only displayed mild clinical signs of BT, if any at all, but six of them experienced pregnancy loss between weeks four and eight of gestation, and five of them became BT PCR and antibody positive. The other two infected heifers gave birth at term to two healthy and BT negative calves. The BT viral load varied among the semen batches used and this had a significant impact on the infection rate, the time of onset of viraemia post artificial insemination, and the gestational stage at which pregnancy loss occurred. These results, which confirm unusual features of BTV-8 infection, should not be extrapolated to infection with other BTV strains without thorough evaluation. This study also adds weight to the hypothesis that the re-emergence of BTV-8 in France in 2015 may be attributable to the use of contaminated bovine semen. Full article

(This article belongs to the Special Issue Bluetongue Virus (BTV))

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10 pages, 2203 KiB

Open AccessCommunication

The VP3 Protein of Bluetongue Virus Associates with the MAVS Complex and Interferes with the RIG-I-Signaling Pathway

by Marie Pourcelot, Rayane Amaral Moraes, Aurore Fablet, Emmanuel Bréard, Corinne Sailleau, Cyril Viarouge, Lydie Postic, Stéphan Zientara, Grégory Caignard and Damien Vitour

Viruses 2021, 13(2), 230; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020230 - 02 Feb 2021

Cited by 7 | Viewed by 1917

Abstract

Bluetongue virus (BTV), an arbovirus transmitted by Culicoides biting midges, is a major concern of wild and domestic ruminants. While BTV induces type I interferon (alpha/beta interferon [IFN-α/β]) production in infected cells, several reports have described evasion strategies elaborated by this virus to [...] Read more.

Bluetongue virus (BTV), an arbovirus transmitted by Culicoides biting midges, is a major concern of wild and domestic ruminants. While BTV induces type I interferon (alpha/beta interferon [IFN-α/β]) production in infected cells, several reports have described evasion strategies elaborated by this virus to dampen this intrinsic, innate response. In the present study, we suggest that BTV VP3 is a new viral antagonist of the IFN-β synthesis. Indeed, using split luciferase and coprecipitation assays, we report an interaction between VP3 and both the mitochondrial adapter protein MAVS and the IRF3-kinase IKKε. Overall, this study describes a putative role for the BTV structural protein VP3 in the control of the antiviral response. Full article

(This article belongs to the Special Issue Bluetongue Virus (BTV))

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21 pages, 2798 KiB

Open AccessArticle

Putative Novel Serotypes ‘33’ and ‘35’ in Clinically Healthy Small Ruminants in Mongolia Expand the Group of Atypical BTV

by Christina Ries, Tumenjargal Sharav, Erdene-Ochir Tseren-Ochir, Martin Beer and Bernd Hoffmann

Viruses 2021, 13(1), 42; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010042 - 29 Dec 2020

Cited by 32 | Viewed by 2479

Abstract

Between 2015 and 2018, we identified the presence of three so-far-unknown Bluetongue virus (BTV) strains (BTV-MNG1/2018, BTV-MNG2/2016, and BTV-MNG3/2016) circulating in clinical healthy sheep and goats in Mongolia. Virus isolation from EDTA blood samples of BTV-MNG1/2018 and BTV-MNG3/2016 was successful on the mammalian [...] Read more.

Between 2015 and 2018, we identified the presence of three so-far-unknown Bluetongue virus (BTV) strains (BTV-MNG1/2018, BTV-MNG2/2016, and BTV-MNG3/2016) circulating in clinical healthy sheep and goats in Mongolia. Virus isolation from EDTA blood samples of BTV-MNG1/2018 and BTV-MNG3/2016 was successful on the mammalian cell line BSR using blood collected from surveillance. After experimental inoculation of goats with BTV-MNG2/2016 positive blood as inoculum, we observed viraemia in one goat and with the EDTA blood of the experimental inoculation, the propagation of BTV-MNG2/2016 in cell culture was successful on mammalian cell line BSR as well. However, virus isolation experiments for BTV-MNG2/2016 on KC cells were unsuccessful. Furthermore, we generated the complete coding sequence of all three novel Mongolian strains. For atypical BTV, serotyping via the traditional serum neutralization assay is not trivial. We therefore sorted the ‘putative novel atypical serotypes’ according to their segment-2 sequence identities and their time point of sampling. Hence, the BTV-MNG1/2018 isolate forms the ‘putative novel atypical serotype’ 33, the BTV-MNG3/2016 the ‘putative novel atypical serotype’ 35, whereas the BTV-MNG2/2016 strain belongs to the same putative novel atypical serotype ‘30’ as BTV-XJ1407 from China. Full article

(This article belongs to the Special Issue Bluetongue Virus (BTV))

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20 pages, 4607 KiB

Open AccessArticle

Identifying Spanish Areas at More Risk of Monthly BTV Transmission with a Basic Reproduction Number Approach

by Cecilia Aguilar-Vega, Jaime Bosch, Eduardo Fernández-Carrión, Javier Lucientes and José Manuel Sánchez-Vizcaíno

Viruses 2020, 12(10), 1158; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101158 - 13 Oct 2020

Cited by 1 | Viewed by 2226

Abstract

Bluetongue virus (BTV) causes a disease that is endemic in Spain and its two major biological vector species, C. imicola and the Obsoletus complex species, differ greatly in their ecology and distribution. Understanding the seasonality of BTV transmission in risk areas is key [...] Read more.

Bluetongue virus (BTV) causes a disease that is endemic in Spain and its two major biological vector species, C. imicola and the Obsoletus complex species, differ greatly in their ecology and distribution. Understanding the seasonality of BTV transmission in risk areas is key to improving surveillance and control programs, as well as to better understand the pathogen transmission networks between wildlife and livestock. Here, monthly risk transmission maps were generated using risk categories based on well-known BTV R₀ equations and predicted abundances of the two most relevant vectors in Spain. Previously, Culicoides spp. predicted abundances in mainland Spain and the Balearic Islands were obtained using remote sensing data and random forest machine learning algorithm. Risk transmission maps were externally assessed with the estimated date of infection of BTV-1 and BTV-4 historical outbreaks. Our results highlight the differences in risk transmission during April-October, June-August being the period with higher R₀ values. Likewise, a natural barrier has been identified between northern and central-southern areas at risk that may hamper BTV spread between them. Our results can be relevant to implement risk-based interventions for the prevention, control and surveillance of BTV and other diseases shared between livestock and wildlife host populations. Full article

(This article belongs to the Special Issue Bluetongue Virus (BTV))

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20 pages, 5879 KiB

Open AccessArticle

Isolation and Cultivation of a New Isolate of BTV-25 and Presumptive Evidence for a Potential Persistent Infection in Healthy Goats

by Christina Ries, Ursula Domes, Britta Janowetz, Jens Böttcher, Katinka Burkhardt, Thomas Miller, Martin Beer and Bernd Hoffmann

Viruses 2020, 12(9), 983; https://0-doi-org.brum.beds.ac.uk/10.3390/v12090983 - 04 Sep 2020

Cited by 15 | Viewed by 2252

Abstract

Recently, several so-called “atypical” Bluetongue virus (BTV) serotypes were discovered, including BTV-25 (Toggenburg virus), in Switzerland. Most “atypical” BTV were identified in small ruminants without clinical signs. In 2018, two goats from a holding in Germany tested positive for BTV-25 genome by RT-qPCR [...] Read more.

Recently, several so-called “atypical” Bluetongue virus (BTV) serotypes were discovered, including BTV-25 (Toggenburg virus), in Switzerland. Most “atypical” BTV were identified in small ruminants without clinical signs. In 2018, two goats from a holding in Germany tested positive for BTV-25 genome by RT-qPCR prior to export. After experimental inoculation of the two goats with the BTV-25 positive field blood samples for generation of reference materials, viremia could be observed in one animal. For the first time, the BTV-25-related virus was isolated in cell culture from EDTA-blood and the full genome of isolate “BTV-25-GER2018” could be generated. BTV-25-GER2018 was only incompletely neutralized by ELISA-positive sera. We could monitor the BTV-25 occurrence in the respective affected goat flock of approximately 120 goats over several years. EDTA blood samples were screened with RT-qPCR using a newly developed BTV-25 specific assay. For serological surveillance, serum samples were screened using a commercial cELISA. BTV-25-GER2018 was detected over 4.5 years in the goat flock with intermittent PCR-positivity in some animals, and with or without concomitantly detected antibodies since 2015. We could demonstrate the viral persistence of BTV-25-GER2018 in goats for up to 4.5 years, and the first BTV-25 isolate is now available for further characterization. Full article

(This article belongs to the Special Issue Bluetongue Virus (BTV))

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11 pages, 2157 KiB

Open AccessArticle

Co-Circulation of Multiple Serotypes of Bluetongue Virus in Zambia

by Herman M. Chambaro, Michihito Sasaki, Edgar Simulundu, Isaac Silwamba, Yona Sinkala, Gabriel Gonzalez, David Squarre, Paul Fandamu, Caesar H. Lubaba, Musso Munyeme, Alikhadio Maseko, Choopa Chimvwele, Liywalii Mataa, Lynnfield E. Mooya, Andrew N. Mukubesa, Hayato Harima, Kenny L. Samui, Hetron M. Munang’andu, Martin Simuunza, King S. Nalubamba, Yongjin Qiu, Michael J. Carr, William W. Hall, Yuki Eshita, Hirofumi Sawa and Yasuko Orba Show full author list Hide full author list

Viruses 2020, 12(9), 963; https://0-doi-org.brum.beds.ac.uk/10.3390/v12090963 - 31 Aug 2020

Cited by 3 | Viewed by 3259

Abstract

Bluetongue (BT) is an arthropod-borne viral disease of ruminants with serious trade and socio-economic implications. Although the disease has been reported in a number of countries in sub-Saharan Africa, there is currently no information on circulating serotypes and disease distribution in Zambia. Following [...] Read more.

Bluetongue (BT) is an arthropod-borne viral disease of ruminants with serious trade and socio-economic implications. Although the disease has been reported in a number of countries in sub-Saharan Africa, there is currently no information on circulating serotypes and disease distribution in Zambia. Following surveillance for BT in domestic and wild ruminants in Zambia, BT virus (BTV) nucleic acid and antibodies were detected in eight of the 10 provinces of the country. About 40% (87/215) of pooled blood samples from cattle and goats were positive for BTV nucleic acid, while one hartebeest pool (1/43) was positive among wildlife samples. Sequence analysis of segment 2 revealed presence of serotypes 3, 5, 7, 12 and 15, with five nucleotypes (B, E, F, G and J) being identified. Segment 10 phylogeny showed Zambian BTV sequences clustering with Western topotype strains from South Africa, intimating likely transboundary spread of BTV in Southern Africa. Interestingly, two Zambian viruses and one isolate from Israel formed a novel clade, which we designated as Western topotype 4. The high seroprevalence (96.2%) in cattle from Lusaka and Central provinces and co-circulation of multiple serotypes showed that BT is widespread, underscoring the need for prevention and control strategies. Full article

(This article belongs to the Special Issue Bluetongue Virus (BTV))

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