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25 pages, 13238 KiB

Open AccessArticle

Uncovering the Underlying Mechanisms Blocking Replication of Bluetongue Virus Serotype 26 (BTV-26) in Culicoides Cells

by Baptiste Monsion, Fauziah Mohd Jaafar, Peter P. C. Mertens and Houssam Attoui

Biomolecules 2023, 13(6), 878; https://doi.org/10.3390/biom13060878 - 23 May 2023

Cited by 1 | Viewed by 2730

Abstract

At least 12 serotypes of ‘atypical’ bluetongue virus (BTV-25 to BTV-36) have been identified to date. These atypical serotypes fail to infect/replicate in Culicoides-derived cell lines and/or adult Culicoides vectors and hence can no longer be transmitted by these vectors. They appear [...] Read more.

At least 12 serotypes of ‘atypical’ bluetongue virus (BTV-25 to BTV-36) have been identified to date. These atypical serotypes fail to infect/replicate in Culicoides-derived cell lines and/or adult Culicoides vectors and hence can no longer be transmitted by these vectors. They appear to be horizontally transmitted from infected to in-contact ruminants, although the route(s) of infection remain to be identified. Viral genome segments 1, 2 and 3 (Seg-1, Seg2 and Seg-3) of BTV-26 were identified as involved in blocking virus replication in KC cells. We have developed Culicoides-specific expression plasmids, which we used in transfected insect cells to assess the stability of viral mRNAs and protein expression from full-length open reading frames of Seg-1, -2 and -3 of BTV-1 (a Culicoides-vectored BTV) or BTV-26. Our results indicate that the blocked replication of BTV-26 in KC cells is not due to an RNAi response, which would lead to rapid degradation of viral mRNAs. A combination of degradation/poor expression and/or modification of the proteins encoded by these segments appears to drive the failure of BTV-26 core/whole virus-particles to assemble and replicate effectively in Culicoides cells. Full article

(This article belongs to the Special Issue New Insight into Vector Borne Diseases)

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9 pages, 246 KiB

Open AccessCommunication

Intravenous Infection of Small Ruminants Suggests a Goat-Restricted Host Tropism and Weak Humoral Immune Response for an Atypical Bluetongue Virus Isolate

by Massimo Spedicato, Giovanni Di Teodoro, Liana Teodori, Mariangela Iorio, Alessandra Leone, Barbara Bonfini, Lilia Testa, Maura Pisciella, Claudia Casaccia, Ottavio Portanti, Emanuela Rossi, Tiziana Di Febo, Nicola Ferri, Giovanni Savini and Alessio Lorusso

Viruses 2023, 15(1), 257; https://doi.org/10.3390/v15010257 - 16 Jan 2023

Viewed by 2276

Abstract

Bluetongue virus (BTV) is the etiologic agent of bluetongue (BT), a viral WOAH-listed disease affecting wild and domestic ruminants, primarily sheep. The outermost capsid protein VP2, encoded by S2, is the virion’s most variable protein, and the ability of reference sera to neutralize [...] Read more.

Bluetongue virus (BTV) is the etiologic agent of bluetongue (BT), a viral WOAH-listed disease affecting wild and domestic ruminants, primarily sheep. The outermost capsid protein VP2, encoded by S2, is the virion’s most variable protein, and the ability of reference sera to neutralize an isolate has so far dictated the differentiation of 24 classical BTV serotypes. Since 2008, additional novel BTV serotypes, often referred to as “atypical” BTVs, have been documented and, currently, the full list includes 36 putative serotypes. In March 2015, a novel atypical BTV strain was detected in the blood of asymptomatic goats in Sardinia (Italy) and named BTV-X ITL2015. The strain re-emerged in the same region in 2021 (BTV-X ITL2021). In this study, we investigated the pathogenicity and kinetics of infection of BTV-X ITL2021 following subcutaneous and intravenous infection of small ruminants. We demonstrated that, in our experimental settings, BTV-X ITL2021 induced a long-lasting viraemia only when administered by the intravenous route in goats, though the animals remained healthy and, apparently, did not develop a neutralizing immune response. Sheep were shown to be refractory to the infection by either route. Our findings suggest a restricted host tropism of BTV-X and point out goats as reservoirs for this virus in the field. Full article

(This article belongs to the Section Animal Viruses)

13 pages, 1203 KiB

Open AccessArticle

Bluetongue Virus Infection of Goats: Re-Emerged European Serotype 8 vs. Two Atypical Serotypes

by Christina Ries, Martin Beer and Bernd Hoffmann

Viruses 2022, 14(5), 1034; https://doi.org/10.3390/v14051034 - 13 May 2022

Cited by 7 | Viewed by 2328

Abstract

In recent years, numerous atypical Bluetongue virus (BTV) strains have been discovered all around the world. Atypical BTV strains are phylogenetically distinct from the classical BTV serotypes 1–24 and differ in terms of several biological features. For the first time, the atypical strains [...] Read more.

In recent years, numerous atypical Bluetongue virus (BTV) strains have been discovered all around the world. Atypical BTV strains are phylogenetically distinct from the classical BTV serotypes 1–24 and differ in terms of several biological features. For the first time, the atypical strains BTV-25-GER2018 and BTV-33-MNG3/2016 as well as the re-emerged classical strain BTV-8-GER2018 were evaluated comparatively in a pathogenesis study in goats—the natural host of atypical BTV. A substantial number of in-contact animals were included in this study to detect potential contact transmissions of the virus. After infection, EDTA blood, ocular, nasal and oral swab samples as well as serum were collected regularly and were used for virological and serological analyses, respectively. Our study showed differences in the immunological reaction between the two atypical BTV strains (no group-specific antibody detection) and the classical BTV strain BTV-8-GER2018 (group-specific antibody detection). Furthermore, we observed an increase in the total WBC count (neutrophils and lymphocytes) in goats infected with the atypical BTV strains. No horizontal transmission was seen for all three strains. Our study suggests that the atypical BTVs used in the trial differ from classical BTVs in their immunopathogenesis. However, no evidence of direct contact transmission was found. Full article

(This article belongs to the Special Issue Emerging and Re-emerging Pathogens of Livestock)

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19 pages, 28734 KiB

Open AccessArticle

Identification of the Genome Segments of Bluetongue Virus Type 26/Type 1 Reassortants Influencing Horizontal Transmission in a Mouse Model

by Houssam Attoui, Baptiste Monsion, Bernard Klonjkowski, Stéphan Zientara, Peter P. C. Mertens and Fauziah Mohd Jaafar

Viruses 2021, 13(11), 2208; https://doi.org/10.3390/v13112208 - 2 Nov 2021

Cited by 8 | Viewed by 3094

Abstract

Bluetongue virus serotypes 1 to 24 are transmitted primarily by infected Culicoides midges, in which they also replicate. However, “atypical” BTV serotypes (BTV-25, -26, -27 and -28) have recently been identified that do not infect and replicate in adult Culicoides, or a [...] Read more.

Bluetongue virus serotypes 1 to 24 are transmitted primarily by infected Culicoides midges, in which they also replicate. However, “atypical” BTV serotypes (BTV-25, -26, -27 and -28) have recently been identified that do not infect and replicate in adult Culicoides, or a Culicoides derived cell line (KC cells). These atypical viruses are transmitted horizontally by direct contact between infected and susceptible hosts (primarily small ruminants) causing only mild clinical signs, although the exact transmission mechanisms involved have yet to be determined. We used reverse genetics to generate a strain of BTV-1 (BTV-1 RG_C7) which is less virulent, infecting IFNAR^(−/−) mice without killing them. Reassortant viruses were also engineered, using the BTV-1 RG_C7 genetic backbone, containing individual genome segments derived from BTV-26. These reassortant viruses were used to explore the genetic control of horizontal transmission (HT) in the IFNAR^(−/−) mouse model. Previous studies showed that genome segments 1, 2 and 3 restrict infection of Culicoides cells, along with a minor role for segment 7. The current study demonstrates that genome segments 2, 5 and 10 of BTV-26 (coding for proteins VP2, NS1 and NS3/NS3a/NS5, respectively) are individually sufficient to promote HT. Full article

(This article belongs to the Section Animal Viruses)

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20 pages, 20515 KiB

Open AccessArticle

An Early Block in the Replication of the Atypical Bluetongue Virus Serotype 26 in Culicoides Cells Is Determined by Its Capsid Proteins

by Marc Guimerà Busquets, Gillian D. Pullinger, Karin E. Darpel, Lyndsay Cooke, Stuart Armstrong, Jennifer Simpson, Massimo Palmarini, Rennos Fragkoudis and Peter P. C. Mertens

Viruses 2021, 13(5), 919; https://doi.org/10.3390/v13050919 - 15 May 2021

Cited by 11 | Viewed by 3998

Abstract

Arboviruses such as bluetongue virus (BTV) replicate in arthropod vectors involved in their transmission between susceptible vertebrate-hosts. The “classical” BTV strains infect and replicate effectively in cells of their insect-vectors (Culicoides biting-midges), as well as in those of their mammalian-hosts (ruminants). However, [...] Read more.

Arboviruses such as bluetongue virus (BTV) replicate in arthropod vectors involved in their transmission between susceptible vertebrate-hosts. The “classical” BTV strains infect and replicate effectively in cells of their insect-vectors (Culicoides biting-midges), as well as in those of their mammalian-hosts (ruminants). However, in the last decade, some “atypical” BTV strains, belonging to additional serotypes (e.g., BTV-26), have been found to replicate efficiently only in mammalian cells, while their replication is severely restricted in Culicoides cells. Importantly, there is evidence that these atypical BTV are transmitted by direct-contact between their mammalian hosts. Here, the viral determinants and mechanisms restricting viral replication in Culicoides were investigated using a classical BTV-1, an “atypical” BTV-26 and a BTV-1/BTV-26 reassortant virus, derived by reverse genetics. Viruses containing the capsid of BTV-26 showed a reduced ability to attach to Culicoides cells, blocking early steps of the replication cycle, while attachment and replication in mammalian cells was not restricted. The replication of BTV-26 was also severely reduced in other arthropod cells, derived from mosquitoes or ticks. The data presented identifies mechanisms and potential barriers to infection and transmission by the newly emerged “atypical” BTV strains in Culicoides. Full article

(This article belongs to the Special Issue Bluetongue Virus: Pathogenesis and Vaccines)

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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://doi.org/10.3390/v13050721 - 21 Apr 2021

Cited by 48 | Viewed by 3365

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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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://doi.org/10.3390/v13010042 - 29 Dec 2020

Cited by 40 | Viewed by 3188

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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19 pages, 1755 KiB

Open AccessReview

Viral Vector Vaccines against Bluetongue Virus

by Luis Jiménez-Cabello, Sergio Utrilla-Trigo, Eva Calvo-Pinilla, Sandra Moreno, Aitor Nogales, Javier Ortego and Alejandro Marín-López

Microorganisms 2021, 9(1), 42; https://doi.org/10.3390/microorganisms9010042 - 25 Dec 2020

Cited by 23 | Viewed by 6329

Abstract

Bluetongue virus (BTV), the prototype member of the genus Orbivirus (family Reoviridae), is the causative agent of an important livestock disease, bluetongue (BT), which is transmitted via biting midges of the genus Culicoides. To date, up to 29 serotypes of BTV have [...] Read more.

Bluetongue virus (BTV), the prototype member of the genus Orbivirus (family Reoviridae), is the causative agent of an important livestock disease, bluetongue (BT), which is transmitted via biting midges of the genus Culicoides. To date, up to 29 serotypes of BTV have been described, which are classified as classical (BTV 1–24) or atypical (serotypes 25–27), and its distribution has been expanding since 1998, with important outbreaks in the Mediterranean Basin and devastating incursions in Northern and Western Europe. Classical vaccine approaches, such as live-attenuated and inactivated vaccines, have been used as prophylactic measures to control BT through the years. However, these vaccine approaches fail to address important matters like vaccine safety profile, effectiveness, induction of a cross-protective immune response among serotypes, and implementation of a DIVA (differentiation of infected from vaccinated animals) strategy. In this context, a wide range of recombinant vaccine prototypes against BTV, ranging from subunit vaccines to recombinant viral vector vaccines, have been investigated. This article offers a comprehensive outline of the live viral vectors used against BTV. Full article

(This article belongs to the Special Issue Bluetongue Virus)

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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://doi.org/10.3390/v12090983 - 4 Sep 2020

Cited by 15 | Viewed by 2932

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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