Rescue of recent virulent and avirulent field strains of Bluetongue virus by reverse genetics

H.G.P. van Gennip, S.G.P. van de Water, C.A. Potgieter, I.M. Wright, D. Veldman, P.A. van Rijn

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)

Abstract

Since 1998, Bluetongue virus (BTV)-serotypes 1, 2, 4, 9, and 16 have invaded European countries around the Mediterranean Basin. In 2006, a huge BT-outbreak started after incursion of BTV-serotype 8 (BTV8) in North-Western Europe. More recently, BTV6 and BTV11 were reported in North-Western Europe in 2008. These latter strains are closely related to live-attenuated vaccine, whereas BTV8 is virulent and can induce severe disease in ruminants, including cattle. In addition, Toggenburg orbivirus (TOV) was detected in 2008 in Swiss goats, which was recognized as a new serotype of BTV (BTV25). The (re) emergency of known and unknown BTV-serotypes needs a rapid response to supply effective vaccines, and research to study this phenomenon. Recently, orbivirus research achieved an important breakthrough by the establishment of reverse genetics for BTV1. Here, reverse genetics for two recent BTV strains representing virulent BTV8 and avirulent BTV6 was developed. For this purpose, extensive sequencing of full-genomes was performed, resulting in the consensus sequences of BTV8/net07 and BTV6/net08. The recovery of 'synthetic BTV', respectively rgBTV8 and rgBTV6, completely from T7-derived RNA transcripts was confirmed by silent mutations by which these 'synthetic BTVs' could be genetically distinguished from wild type BTV, respectively wtBTV6 and wtBTV8. The in vitro and in vivo properties of rgBTV6 or rgBTV8 were comparable to the properties of their parent strains. The asymptomatic or avirulent properties of rgBTV6 and the virulence of rgBTV8 were confirmed by experimental infection of sheep. Reverse genetics of the vaccine-related BTV6 provides a perfect start to develop new generations of BT-vaccines. Reverse genetics of the virulent BTV8 will accelerate research on the special features of BTV8, like transmission by species of Culicoides in a moderate climate, transplacental transmission, and pathogenesis in cattle.
Original languageEnglish
Article numbere30540
JournalPLoS ONE
Volume7
Issue number2
DOIs
Publication statusPublished - 2012

Fingerprint

Bluetongue virus
Reverse Genetics
Viruses
serotypes
Orbivirus
Vaccines
Attenuated Vaccines
live vaccines
Research
Western European region
vaccines
Ceratopogonidae
Serogroup
Genetics
Consensus Sequence
Ruminants
Toggenburg
Climate
Genes
Goats

Keywords

  • protein
  • europe
  • replication
  • trafficking
  • netherlands
  • serotype-8
  • infection
  • epidemic
  • belgium
  • release

Cite this

van Gennip, H. G. P., van de Water, S. G. P., Potgieter, C. A., Wright, I. M., Veldman, D., & van Rijn, P. A. (2012). Rescue of recent virulent and avirulent field strains of Bluetongue virus by reverse genetics. PLoS ONE, 7(2), [e30540]. https://doi.org/10.1371/journal.pone.0030540
van Gennip, H.G.P. ; van de Water, S.G.P. ; Potgieter, C.A. ; Wright, I.M. ; Veldman, D. ; van Rijn, P.A. / Rescue of recent virulent and avirulent field strains of Bluetongue virus by reverse genetics. In: PLoS ONE. 2012 ; Vol. 7, No. 2.
@article{ec13107241ca44daaab10e5e9b8940dc,
title = "Rescue of recent virulent and avirulent field strains of Bluetongue virus by reverse genetics",
abstract = "Since 1998, Bluetongue virus (BTV)-serotypes 1, 2, 4, 9, and 16 have invaded European countries around the Mediterranean Basin. In 2006, a huge BT-outbreak started after incursion of BTV-serotype 8 (BTV8) in North-Western Europe. More recently, BTV6 and BTV11 were reported in North-Western Europe in 2008. These latter strains are closely related to live-attenuated vaccine, whereas BTV8 is virulent and can induce severe disease in ruminants, including cattle. In addition, Toggenburg orbivirus (TOV) was detected in 2008 in Swiss goats, which was recognized as a new serotype of BTV (BTV25). The (re) emergency of known and unknown BTV-serotypes needs a rapid response to supply effective vaccines, and research to study this phenomenon. Recently, orbivirus research achieved an important breakthrough by the establishment of reverse genetics for BTV1. Here, reverse genetics for two recent BTV strains representing virulent BTV8 and avirulent BTV6 was developed. For this purpose, extensive sequencing of full-genomes was performed, resulting in the consensus sequences of BTV8/net07 and BTV6/net08. The recovery of 'synthetic BTV', respectively rgBTV8 and rgBTV6, completely from T7-derived RNA transcripts was confirmed by silent mutations by which these 'synthetic BTVs' could be genetically distinguished from wild type BTV, respectively wtBTV6 and wtBTV8. The in vitro and in vivo properties of rgBTV6 or rgBTV8 were comparable to the properties of their parent strains. The asymptomatic or avirulent properties of rgBTV6 and the virulence of rgBTV8 were confirmed by experimental infection of sheep. Reverse genetics of the vaccine-related BTV6 provides a perfect start to develop new generations of BT-vaccines. Reverse genetics of the virulent BTV8 will accelerate research on the special features of BTV8, like transmission by species of Culicoides in a moderate climate, transplacental transmission, and pathogenesis in cattle.",
keywords = "protein, europe, replication, trafficking, netherlands, serotype-8, infection, epidemic, belgium, release",
author = "{van Gennip}, H.G.P. and {van de Water}, S.G.P. and C.A. Potgieter and I.M. Wright and D. Veldman and {van Rijn}, P.A.",
year = "2012",
doi = "10.1371/journal.pone.0030540",
language = "English",
volume = "7",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

van Gennip, HGP, van de Water, SGP, Potgieter, CA, Wright, IM, Veldman, D & van Rijn, PA 2012, 'Rescue of recent virulent and avirulent field strains of Bluetongue virus by reverse genetics', PLoS ONE, vol. 7, no. 2, e30540. https://doi.org/10.1371/journal.pone.0030540

Rescue of recent virulent and avirulent field strains of Bluetongue virus by reverse genetics. / van Gennip, H.G.P.; van de Water, S.G.P.; Potgieter, C.A.; Wright, I.M.; Veldman, D.; van Rijn, P.A.

In: PLoS ONE, Vol. 7, No. 2, e30540, 2012.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Rescue of recent virulent and avirulent field strains of Bluetongue virus by reverse genetics

AU - van Gennip, H.G.P.

AU - van de Water, S.G.P.

AU - Potgieter, C.A.

AU - Wright, I.M.

AU - Veldman, D.

AU - van Rijn, P.A.

PY - 2012

Y1 - 2012

N2 - Since 1998, Bluetongue virus (BTV)-serotypes 1, 2, 4, 9, and 16 have invaded European countries around the Mediterranean Basin. In 2006, a huge BT-outbreak started after incursion of BTV-serotype 8 (BTV8) in North-Western Europe. More recently, BTV6 and BTV11 were reported in North-Western Europe in 2008. These latter strains are closely related to live-attenuated vaccine, whereas BTV8 is virulent and can induce severe disease in ruminants, including cattle. In addition, Toggenburg orbivirus (TOV) was detected in 2008 in Swiss goats, which was recognized as a new serotype of BTV (BTV25). The (re) emergency of known and unknown BTV-serotypes needs a rapid response to supply effective vaccines, and research to study this phenomenon. Recently, orbivirus research achieved an important breakthrough by the establishment of reverse genetics for BTV1. Here, reverse genetics for two recent BTV strains representing virulent BTV8 and avirulent BTV6 was developed. For this purpose, extensive sequencing of full-genomes was performed, resulting in the consensus sequences of BTV8/net07 and BTV6/net08. The recovery of 'synthetic BTV', respectively rgBTV8 and rgBTV6, completely from T7-derived RNA transcripts was confirmed by silent mutations by which these 'synthetic BTVs' could be genetically distinguished from wild type BTV, respectively wtBTV6 and wtBTV8. The in vitro and in vivo properties of rgBTV6 or rgBTV8 were comparable to the properties of their parent strains. The asymptomatic or avirulent properties of rgBTV6 and the virulence of rgBTV8 were confirmed by experimental infection of sheep. Reverse genetics of the vaccine-related BTV6 provides a perfect start to develop new generations of BT-vaccines. Reverse genetics of the virulent BTV8 will accelerate research on the special features of BTV8, like transmission by species of Culicoides in a moderate climate, transplacental transmission, and pathogenesis in cattle.

AB - Since 1998, Bluetongue virus (BTV)-serotypes 1, 2, 4, 9, and 16 have invaded European countries around the Mediterranean Basin. In 2006, a huge BT-outbreak started after incursion of BTV-serotype 8 (BTV8) in North-Western Europe. More recently, BTV6 and BTV11 were reported in North-Western Europe in 2008. These latter strains are closely related to live-attenuated vaccine, whereas BTV8 is virulent and can induce severe disease in ruminants, including cattle. In addition, Toggenburg orbivirus (TOV) was detected in 2008 in Swiss goats, which was recognized as a new serotype of BTV (BTV25). The (re) emergency of known and unknown BTV-serotypes needs a rapid response to supply effective vaccines, and research to study this phenomenon. Recently, orbivirus research achieved an important breakthrough by the establishment of reverse genetics for BTV1. Here, reverse genetics for two recent BTV strains representing virulent BTV8 and avirulent BTV6 was developed. For this purpose, extensive sequencing of full-genomes was performed, resulting in the consensus sequences of BTV8/net07 and BTV6/net08. The recovery of 'synthetic BTV', respectively rgBTV8 and rgBTV6, completely from T7-derived RNA transcripts was confirmed by silent mutations by which these 'synthetic BTVs' could be genetically distinguished from wild type BTV, respectively wtBTV6 and wtBTV8. The in vitro and in vivo properties of rgBTV6 or rgBTV8 were comparable to the properties of their parent strains. The asymptomatic or avirulent properties of rgBTV6 and the virulence of rgBTV8 were confirmed by experimental infection of sheep. Reverse genetics of the vaccine-related BTV6 provides a perfect start to develop new generations of BT-vaccines. Reverse genetics of the virulent BTV8 will accelerate research on the special features of BTV8, like transmission by species of Culicoides in a moderate climate, transplacental transmission, and pathogenesis in cattle.

KW - protein

KW - europe

KW - replication

KW - trafficking

KW - netherlands

KW - serotype-8

KW - infection

KW - epidemic

KW - belgium

KW - release

U2 - 10.1371/journal.pone.0030540

DO - 10.1371/journal.pone.0030540

M3 - Article

VL - 7

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 2

M1 - e30540

ER -