1887

Abstract

Schmallenberg virus (SBV) belongs to the Simbu serogroup within the family , genus and is transmitted by biting midges. Infection of naïve ruminants in a critical phase of gestation may lead to severe congenital malformations. Sequence analysis from viremic animals revealed a very high genome stability. In contrast, sequence variations are frequently described for SBV from malformed fetuses. In addition to S segment mutations, especially within the M segment encoding the major immunogen Gc, point mutations or genomic deletions are also observed. Analysis of the SBV_D281/12 isolate from a malformed fetus revealed multiple point mutations in all three genome segments. It also has a large genomic deletion in the antigenic domain encoded by the M segment compared to the original SBV reference strain ‘BH80/11’ isolated from viremic blood in 2011. Interestingly, SBV_D281/12 showed a marked replication deficiency in cells (KC cells), but not in standard baby hamster kidney cells (BHK-21). We therefore generated a set of chimeric viruses of rSBV_D281/12 and wild-type rSBV_BH80/11 by reverse genetics, which were characterized in both KC and BHK-21 cells. It could be shown that the S segment of SBV_D281/12 is responsible for the replication deficit and that it acts independently from the large deletion within Gc. In addition, a single point mutation at position 111 (S to N) of the nucleoprotein was identified as the critical mutation. Our results suggest that virus variants found in malformed fetuses and carrying characteristic genomic mutations may have a clear ‘loss of fitness’ for their insect hosts . It can also be concluded that such mutations lead to virus variants that are no longer part of the natural transmission cycle between mammalian and insect hosts. Interestingly, analysis of a series of SBV sequences confirmed the S111N mutation exclusively in samples of malformed fetuses and not in blood from viremic animals. The characterization of these changes will allow the definition of protein functions that are critical for only one group of hosts.

Funding
This study was supported by the:
  • German Federal Ministry of Food and Agriculture (BMEL) through the Federal Office for Agriculture and Food (BLE) (Award 281B101816 and 28N207601)
    • Principle Award Recipient: MartinBeer
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.002005
2024-06-26
2024-07-15
Loading full text...

Full text loading...

References

  1. Hoffmann B, Scheuch M, Höper D, Jungblut R, Holsteg M et al. Novel orthobunyavirus in cattle, Europe, 2011. Emerg Infect Dis 2012; 18:469–472 [View Article]
    [Google Scholar]
  2. Wernike K, Beer M. Schmallenberg virus: a novel virus of veterinary importance. Adv Virus Res 2017; 99:39–60 [View Article] [PubMed]
    [Google Scholar]
  3. EFSA “Schmallenberg” virus: analysis of the epidemiological data (May 2013). EFSA Supporting Publications 2013 EN-3429; 2013 http://wwwefsaeuropaeu/de/supporting/doc/429epdf accessed 15 July 2013
  4. European Food Safety Authority Schmallenberg virus: State of Art. EFSA J 2014; 12:54 [View Article]
    [Google Scholar]
  5. Wernike K, Conraths F, Zanella G, Granzow H, Gache K et al. Schmallenberg virus-two years of experiences. Prev Vet Med 2014; 116:423–434 [View Article] [PubMed]
    [Google Scholar]
  6. Bilk S, Schulze C, Fischer M, Beer M, Hlinak A et al. Organ distribution of Schmallenberg virus RNA in malformed newborns. Vet Microbiol 2012; 159:236–238 [View Article] [PubMed]
    [Google Scholar]
  7. Elliott RM, Blakqori G. Molecular biology of orthobunyaviruses. In Plyusnin A, Elliott RM. eds Bunyaviridae: Molecular and Cellular Biology Norfolk, UK: Caister Academic Press; 2011
    [Google Scholar]
  8. Shi X, Lappin DF, Elliott RM. Mapping the Golgi targeting and retention signal of Bunyamwera virus glycoproteins. J Virol 2004; 78:10793–10802 [View Article] [PubMed]
    [Google Scholar]
  9. Shi X, van Mierlo JT, French A, Elliott RM. Visualizing the replication cycle of bunyamwera orthobunyavirus expressing fluorescent protein-tagged Gc glycoprotein. J Virol 2010; 84:8460–8469 [View Article] [PubMed]
    [Google Scholar]
  10. Roman-Sosa G, Karger A, Kraatz F, Aebischer A, Wernike K et al. The amino terminal subdomain of glycoprotein Gc of Schmallenberg virus: disulfide bonding and structural determinants of neutralization. J Gen Virol 2017; 98:1259–1273 [View Article] [PubMed]
    [Google Scholar]
  11. Wernike K, Hoffmann B, Conraths FJ, Beer M. Schmallenberg virus recurrence, Germany, 2014. Emerg Infect Dis 2015; 21:1202–1204 [View Article] [PubMed]
    [Google Scholar]
  12. Fischer M, Hoffmann B, Goller KV, Höper D, Wernike K et al. A mutation “hot spot” in the Schmallenberg virus M segment. J Gen Virol 2013; 94:1161–1167 [View Article] [PubMed]
    [Google Scholar]
  13. Coupeau D, Claine F, Wiggers L, Kirschvink N, Muylkens B. In vivo and in vitro identification of a hypervariable region in Schmallenberg virus. J Gen Virol 2013; 94:1168–1174 [View Article] [PubMed]
    [Google Scholar]
  14. Wernike K, Beer M. Misinterpretation of Schmallenberg virus sequence variations: the sample material makes the difference. Virus Genes 2019; 55:123–126 [View Article] [PubMed]
    [Google Scholar]
  15. Wernike K, Reimann I, Banyard AC, Kraatz F, La Rocca SA et al. High genetic variability of Schmallenberg virus M-segment leads to efficient immune escape from neutralizing antibodies. PLoS Pathog 2021; 17:e1009247 [View Article] [PubMed]
    [Google Scholar]
  16. Kärber G. Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche. Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie 1931; 162:480–483 [View Article]
    [Google Scholar]
  17. Spearman C. The method of “right and wrong cases” ('constant stimuli’) withour Gauss’s formulae. British J Psychol 1908; 2:227–242 [View Article]
    [Google Scholar]
  18. Geiser M, Cèbe R, Drewello D, Schmitz R. Integration of PCR fragments at any specific site within cloning vectors without the use of restriction enzymes and DNA ligase. Biotech Tech Rep 2001; 31:88–90 [View Article] [PubMed]
    [Google Scholar]
  19. Habjan M, Andersson I, Klingström J, Schümann M, Martin A et al. Processing of genome 5’ termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction. PLoS One 2008; 3:e2032 [View Article] [PubMed]
    [Google Scholar]
  20. Kraatz F, Wernike K, Hechinger S, König P, Granzow H et al. Deletion mutants of Schmallenberg virus are avirulent and protect from virus challenge. J Virol 2015; 89:1825–1837 [View Article] [PubMed]
    [Google Scholar]
  21. Wernike K, Brocchi E, Cordioli P, Sénéchal Y, Schelp C et al. A novel panel of monoclonal antibodies against Schmallenberg virus nucleoprotein and glycoprotein Gc allows specific orthobunyavirus detection and reveals antigenic differences. Vet Res 2015; 46:27 [View Article] [PubMed]
    [Google Scholar]
  22. Hellert J, Aebischer A, Wernike K, Haouz A, Brocchi E et al. Orthobunyavirus spike architecture and recognition by neutralizing antibodies. Nat Commun 2019; 10:879 [View Article] [PubMed]
    [Google Scholar]
  23. Roman-Sosa G, Brocchi E, Schirrmeier H, Wernike K, Schelp C et al. Analysis of the humoral immune response against the envelope glycoprotein Gc of Schmallenberg virus reveals a domain located at the amino terminus targeted by mAbs with neutralizing activity. J Gen Virol 2016; 97:571–580 [View Article] [PubMed]
    [Google Scholar]
  24. van Gennip RGP, Drolet BS, Rozo Lopez P, Roost AJC, Boonstra J et al. Vector competence is strongly affected by a small deletion or point mutations in bluetongue virus. Parasit Vectors 2019; 12:470 [View Article] [PubMed]
    [Google Scholar]
  25. Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog 2007; 3:e201 [View Article] [PubMed]
    [Google Scholar]
  26. Sick F, Breithaupt A, Golender N, Bumbarov V, Beer M et al. Shuni virus-induced meningoencephalitis after experimental infection of cattle. Transbound Emerg Dis 2021; 68:1531–1540 [View Article] [PubMed]
    [Google Scholar]
  27. Hulst M, Kortekaas J, Hakze-van der Honing R, Vastenhouw S, Cornellissen J et al. Genetic characterization of an atypical Schmallenberg virus isolated from the brain of a malformed lamb. Virus Genes 2013; 47:505–514 [View Article] [PubMed]
    [Google Scholar]
  28. Tonbak Ş, Azkur AK, Pesti̇l Z, Biyikli E, Abayli H et al. Circulation of Schmallenberg virus in Turkey, 2013. Turk J Vet Anim Sci 2016; 40:175–180 [View Article]
    [Google Scholar]
  29. Coupeau D, Claine F, Wiggers L, Kirschvink N, Muylkens B. S segment variability during the two first years of the spread of Schmallenberg virus. Arch Virol 2016; 161:1353–1358 [View Article] [PubMed]
    [Google Scholar]
  30. Fehér E, Marton S, Tóth ÁG, Ursu K, Wernike K et al. Sequence analysis of Schmallenberg virus genomes detected in Hungary. Acta Microbiol Immunol Hung 2017; 64:373–384 [View Article] [PubMed]
    [Google Scholar]
  31. Kęsik-Maliszewska J, Antos A, Rola J, Larska M. Comparison of Schmallenberg virus sequences isolated from mammal host and arthropod vector. Virus Genes 2018; 54: [View Article] [PubMed]
    [Google Scholar]
  32. McGowan SL, La Rocca SA, Grierson SS, Dastjerdi A, Choudhury B et al. Incursion of Schmallenberg virus into Great Britain in 2011 and emergence of variant sequences in 2016. Vet J 2018; 234:77–84 [View Article] [PubMed]
    [Google Scholar]
  33. Behar A, Izhaki O, Rot A, Benor T, Yankilevich M et al. Genomic detection of Schmallenberg virus, Israel. Emerg Infect Dis 2021; 27:2197–2200 [View Article] [PubMed]
    [Google Scholar]
  34. Yilmaz H, Hoffmann B, Turan N, Cizmecigil UY, Richt JA et al. Detection and partial sequencing of Schmallenberg virus in cattle and sheep in Turkey. Vector Borne Zoonotic Dis 2014; 14:223–225 [View Article] [PubMed]
    [Google Scholar]
  35. Ciota AT, Kramer LD. Insights into arbovirus evolution and adaptation from experimental studies. Viruses 2010; 2:2594–2617 [View Article] [PubMed]
    [Google Scholar]
  36. Ariza A, Tanner SJ, Walter CT, Dent KC, Shepherd DA et al. Nucleocapsid protein structures from orthobunyaviruses reveal insight into ribonucleoprotein architecture and RNA polymerization. Nucleic Acids Res 2013; 41:5912–5926 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.002005
Loading
/content/journal/jgv/10.1099/jgv.0.002005
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error