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Home / Equine Research Bank / J Virol / VP2 Exchange and NS3/NS3a Deletion in African Horse Sickness...
Journal of virology2015; 89(17); 8764-8772; doi: 10.1128/JVI.01052-15

VP2 Exchange and NS3/NS3a Deletion in African Horse Sickness Virus (AHSV) in Development of Disabled Infectious Single Animal Vaccine Candidates for AHSV.

Abstract: African horse sickness virus (AHSV) is a virus species in the genus Orbivirus of the family Reoviridae. There are nine serotypes of AHSV showing different levels of cross neutralization. AHSV is transmitted by species of Culicoides biting midges and causes African horse sickness (AHS) in equids, with a mortality rate of up to 95% in naive horses. AHS has become a serious threat for countries outside Africa, since endemic Culicoides species in moderate climates appear to be competent vectors for the related bluetongue virus (BTV). To control AHS, live-attenuated vaccines (LAVs) are used in Africa. We used reverse genetics to generate "synthetic" reassortants of AHSV for all nine serotypes by exchange of genome segment 2 (Seg-2). This segment encodes VP2, which is the serotype-determining protein and the dominant target for neutralizing antibodies. Single Seg-2 AHSV reassortants showed similar cytopathogenic effects in mammalian cells but displayed different growth kinetics. Reverse genetics for AHSV was also used to study Seg-10 expressing NS3/NS3a proteins. We demonstrated that NS3/NS3a proteins are not essential for AHSV replication in vitro. NS3/NS3a of AHSV is, however, involved in the cytopathogenic effect in mammalian cells and is very important for virus release from cultured insect cells in particular. Similar to the concept of the bluetongue disabled infectious single animal (BT DISA) vaccine platform, an AHS DISA vaccine platform lacking NS3/NS3a expression was developed. Using exchange of genome segment 2 encoding VP2 protein (Seg-2[VP2]), we will be able to develop AHS DISA vaccine candidates for all current AHSV serotypes. Objective: African horse sickness virus is transmitted by species of Culicoides biting midges and causes African horse sickness in equids, with a mortality rate of up to 95% in naive horses. African horse sickness has become a serious threat for countries outside Africa, since endemic Culicoides species in moderate climates are supposed to be competent vectors. By using reverse genetics, viruses of all nine serotypes were constructed by the exchange of Seg-2 expressing the serotype-determining VP2 protein. Furthermore, we demonstrated that the nonstructural protein NS3/NS3a is not essential for virus replication in vitro. However, the potential spread of the virus by biting midges is supposed to be blocked, since the in vitro release of the virus was strongly reduced due to this deletion. VP2 exchange and NS3/NS3a deletion in African horse sickness virus were combined in the concept of a disabled infectious single animal vaccine for all nine serotypes.
Copyright © 2015, van de Water et al.
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Publication Date: 2015-06-10 PubMed ID: 26063433PubMed Central: PMC4524073DOI: 10.1128/JVI.01052-15Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the development of a single animal vaccine for African horse sickness virus (AHSV) using VP2 exchange and NS3/NS3a deletion techniques.

Understanding African Horse Sickness Virus (AHSV)

  • AHSV is a virus species that belongs to the Orbivirus genus of the Reoviridae family.
  • There are nine serotypes of AHSV, each exhibiting different levels of cross neutralization.
  • AHSV is contracted by equines through the bite of Culicoides biting midges which result in African horse sickness (AHS).
  • AHS has a mortality rate as high as 95% in naive horses and is a rising threat in countries outside Africa where Culicoides species in moderate climates can act as competent vectors.

Strategies for AHSV Control

  • In Africa, live-attenuated vaccines (LAVs) are used for AHSV control. New strategies are being developed using reverse genetics to generate “synthetic” reassortants of AHSV for all the nine serotypes by swapping genome segment 2 (Seg-2).
  • Seg-2 encodes for VP2 protein, which helps in determining the serotype and is the dominant target for neutralizing antibodies.
  • The study found that the single Seg-2 AHSV reassortants had similar cytopathogenic effects in mammalian cells but exhibited different growth kinetics.

Role of NS3/NS3a Proteins in AHSV

  • It was observed that NS3/NS3a proteins were not necessary for AHSV replication in vitro. However, they played a major role in causing the cytopathogenic effect in mammalian cells and were crucial for the virus release from cultured insect cells.
  • A new vaccine platform for AHS was developed using the disabled infectious single animal (DISA) concept. In this platform, the NS3/NS3a expression was absent. This concept is similar to the bluetongue disabled infectious single animal (BT DISA) vaccine platform.
  • The researchers believe that the AHS DISA vaccine candidates for all current AHSV serotypes can be developed by utilising the exchange of genome segment 2 encoding VP2 protein (Seg-2[VP2]).

To sum up, AHSV causes a fatal horse sickness, and this study dives deep into the genetics of AHSV, particularly focusing on the role and potential manipulations of Seg-2 (which encodes for the VP2 protein), as well as NS3/NS3a proteins. The research leads to the development of a new vaccine platform that could potentially create effective vaccines for all nine serotypes of AHSV.

Cite This Article

APA
van de Water SG, van Gennip RG, Potgieter CA, Wright IM, van Rijn PA. (2015). VP2 Exchange and NS3/NS3a Deletion in African Horse Sickness Virus (AHSV) in Development of Disabled Infectious Single Animal Vaccine Candidates for AHSV. J Virol, 89(17), 8764-8772. https://doi.org/10.1128/JVI.01052-15

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 89
Issue: 17
Pages: 8764-8772

Researcher Affiliations

van de Water, Sandra G P
  • Department of Virology, Central Veterinary Institute of Wageningen UR (CVI), Lelystad, The Netherlands.
van Gennip, René G P
  • Department of Virology, Central Veterinary Institute of Wageningen UR (CVI), Lelystad, The Netherlands.
Potgieter, Christiaan A
  • Deltamune (Pty.) Ltd., Lyttelton, Centurion, South Africa Department of Biochemistry, Centre for Human Metabonomics, North-West University, Potchefstroom, South Africa.
Wright, Isabel M
  • Deltamune (Pty.) Ltd., Lyttelton, Centurion, South Africa.
van Rijn, Piet A
  • Department of Virology, Central Veterinary Institute of Wageningen UR (CVI), Lelystad, The Netherlands Department of Biochemistry, Centre for Human Metabonomics, North-West University, Potchefstroom, South Africa piet.vanrijn@wur.nl.

MeSH Terms

  • African Horse Sickness / immunology
  • African Horse Sickness / prevention & control
  • African Horse Sickness / virology
  • African Horse Sickness Virus / genetics
  • African Horse Sickness Virus / immunology
  • African Horse Sickness Virus / metabolism
  • Animals
  • Antibodies, Neutralizing / immunology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Cell Line
  • Ceratopogonidae / virology
  • Cricetinae
  • Genome, Viral / genetics
  • Horses / immunology
  • Horses / virology
  • Mutation / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, Subunit / immunology
  • Viral Nonstructural Proteins / genetics
  • Viral Vaccines / immunology
  • Virus Replication / genetics

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