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Viruses
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Bluetongue Virus: Pathogenesis and Vaccines
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Bluetongue Virus: Pathogenesis and Vaccines

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 11083

Special Issue Editors

Dr. Noemí Sevilla

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Guest Editor
Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria, Madrid, Spain
Interests: ruminant viruses; viral immunology; adenovirus-based vaccines
Special Issues, Collections and Topics in MDPI journals
Dr. Verónica Martín

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Guest Editor
Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria, Madrid, Spain
Special Issues, Collections and Topics in MDPI journals
Dr. José M. Rojas

E-Mail Website
Guest Editor
Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria, Madrid, Spain
Interests: immunology; vaccines; virus; immune response; sheep; BTV; PPRV
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bluetongue virus (BTV) is a dsRNA virus (family Reoviridae, genus Orbivirus) transmitted by insect vectors (Culicoides spp.). BTV infects domestic and wild ruminants and causes high morbidity and mortality, mainly in sheep. Bluetongue is a World Organization for Animal Health (OIE) listed disease due to the great socioeconomic losses it inflicts. The presence of BTV has been documented on all continents except for Antarctica, reflecting the geographical expansion of Culicoides vectors. There are at least 29 BTV serotypes, which are based on the specific humoral response elicited against the VP2 protein. It has been shown that the reassortment of BTV RNA segments is responsible for the appearance of new virus strains.

Improved understanding of key factors involved in host tropism, immune response, and vaccine efficacy is required for the development of safe and potent new-generation BTV vaccines that have DIVA potential and are applicable to all serotypes (due to the frequent emergence of novel BTV serotypes). Therefore, this Special Issue welcomes all types of manuscripts (e.g., reviews, research articles, and short communications) addressing molecular mechanisms, host–virus interactions, pathogenicity, and vaccine strategies.

Dr. Noemí Sevilla
Dr. Veronica Martín
Dr. Jose M. Rojas
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bluetongue virus
  • vaccines
  • pathogenesis
  • immune response
  • host tropism
  • host–virus interaction

Published Papers (4 papers)

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Research

24 pages, 4431 KiB  
Article
Serological Cross-Reactions between Expressed VP2 Proteins from Different Bluetongue Virus Serotypes
by Petra C. Fay, Fauziah Mohd Jaafar, Carrie Batten, Houssam Attoui, Keith Saunders, George P. Lomonossoff, Elizabeth Reid, Daniel Horton, Sushila Maan, David Haig, Janet M. Daly and Peter P. C. Mertens
Viruses 2021, 13(8), 1455; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081455 - 26 Jul 2021
Cited by 5 | Viewed by 2853
Abstract
Bluetongue (BT) is a severe and economically important disease of ruminants that is widely distributed around the world, caused by the bluetongue virus (BTV). More than 28 different BTV serotypes have been identified in serum neutralisation tests (SNT), which, along with geographic variants [...] Read more.
Bluetongue (BT) is a severe and economically important disease of ruminants that is widely distributed around the world, caused by the bluetongue virus (BTV). More than 28 different BTV serotypes have been identified in serum neutralisation tests (SNT), which, along with geographic variants (topotypes) within each serotype, reflect differences in BTV outer-capsid protein VP2. VP2 is the primary target for neutralising antibodies, although the basis for cross-reactions and serological variations between and within BTV serotypes is poorly understood. Recombinant BTV VP2 proteins (rVP2) were expressed in Nicotiana benthamiana, based on sequence data for isolates of thirteen BTV serotypes (primarily from Europe), including three ‘novel’ serotypes (BTV-25, -26 and -27) and alternative topotypes of four serotypes. Cross-reactions within and between these viruses were explored using rabbit anti-rVP2 sera and post BTV-infection sheep reference-antisera, in I-ELISA (with rVP2 target antigens) and SNT (with reference strains of BTV-1 to -24, -26 and -27). Strong reactions were generally detected with homologous rVP2 proteins or virus strains/serotypes. The sheep antisera were largely serotype-specific in SNT, but more cross-reactive by ELISA. Rabbit antisera were more cross-reactive in SNT, and showed widespread, high titre cross-reactions against homologous and heterologous rVP2 proteins in ELISA. Results were analysed and visualised by antigenic cartography, showing closer relationships in some, but not all cases, between VP2 topotypes within the same serotype, and between serotypes belonging to the same ‘VP2 nucleotype’. Full article
(This article belongs to the Special Issue Bluetongue Virus: Pathogenesis and Vaccines)
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18 pages, 3506 KiB  
Article
Inhibition of Orbivirus Replication by Fluvastatin and Identification of the Key Elements of the Mevalonate Pathway Involved
by Fauziah Mohd Jaafar, Baptiste Monsion, Mourad Belhouchet, Peter P. C. Mertens and Houssam Attoui
Viruses 2021, 13(8), 1437; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081437 - 23 Jul 2021
Cited by 7 | Viewed by 2384
Abstract
Statin derivatives can inhibit the replication of a range of viruses, including hepatitis C virus (HCV, Hepacivirus), dengue virus (Flavivirus), African swine fever virus (Asfarviridae) and poliovirus (Picornaviridae). We assess the antiviral effect of fluvastatin in [...] Read more.
Statin derivatives can inhibit the replication of a range of viruses, including hepatitis C virus (HCV, Hepacivirus), dengue virus (Flavivirus), African swine fever virus (Asfarviridae) and poliovirus (Picornaviridae). 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. Full article
(This article belongs to the Special Issue Bluetongue Virus: Pathogenesis and Vaccines)
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20 pages, 20515 KiB  
Article
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://0-doi-org.brum.beds.ac.uk/10.3390/v13050919 - 15 May 2021
Cited by 9 | Viewed by 3037
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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13 pages, 1979 KiB  
Article
The Bluetongue Disabled Infectious Single Animal (DISA) Vaccine Platform Based on Deletion NS3/NS3a Protein Is Safe and Protective in Cattle and Enables DIVA
by Piet A. van Rijn, Mieke A. Maris-Veldhuis and René G. P. van Gennip
Viruses 2021, 13(5), 857; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050857 - 07 May 2021
Cited by 4 | Viewed by 2116
Abstract
The bluetongue virus (BTV) is transmitted by Culicoides biting midges and causes bluetongue (BT), an OIE-notifiable disease of ruminants. At least 29 BTV serotypes are described as determined by the outer shell proteins VP2 and VP5. Vaccination is the most effective control measure. [...] Read more.
The bluetongue virus (BTV) is transmitted by Culicoides biting midges and causes bluetongue (BT), an OIE-notifiable disease of ruminants. At least 29 BTV serotypes are described as determined by the outer shell proteins VP2 and VP5. Vaccination is the most effective control measure. Inactivated and live-attenuated vaccines (LAVs) are currently available. These vaccines have their specific pros and cons, and both are not DIVA vaccines. The BT Disabled Infectious Single Animal (DISA) vaccine platform is based on LAV without nonessential NS3/NS3a expression and is applicable for many serotypes by the exchange of outer shell proteins. The DISA vaccine is effective and completely safe. Further, transmission of the DISA vaccine by midges is blocked (DISA principle). Finally, the DISA vaccine enables DIVA because of a lack of antibodies against the immunogenic NS3/NS3a protein (DIVA principle). The deletion of 72 amino acids (72aa) in NS3/NS3a is sufficient to block virus propagation in midges. Here, we show that a prototype DISA vaccine based on LAV with the 72aa deletion enables DIVA, is completely safe and induces a long-lasting serotype-specific protection in cattle. In conclusion, the in-frame deletion of 72-aa codons in the BT DISA/DIVA vaccine platform is sufficient to fulfil all the criteria for modern veterinary vaccines. Full article
(This article belongs to the Special Issue Bluetongue Virus: Pathogenesis and Vaccines)
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