1887

Journal of General Virology header logo

Volume 96, Issue 3

Modification of a salmonid alphavirus replicon vector for enhanced expression of heterologous antigens Free

Abstract

A salmonid alphavirus (SAV) replicon has been developed to express heterologous antigens but protein production was low to modest compared with terrestrial alphavirus replicons. In this study, we have compared several modifications to a SAV replicon construct and analysed their influence on foreign gene expression. We found that an insertion of a translational enhancer consisting of the N-terminal 102 nt of the capsid gene, together with a nucleotide sequence encoding the foot-and-mouth disease virus (FMDV) 2A peptide, caused a significant increase in EGFP reporter gene expression. The importance of fusing a hammerhead (HH) ribozyme sequence at the 5′ end of the viral genome was also demonstrated. In contrast, a hepatitis D virus ribozyme (HDV-RZ) sequence placed at the 3′ end did not augment expression of inserted genes. Taken together, we have developed a platform for optimized antigen production, which can be applied for immunization of salmonid fish in the future.

  • Received:
  • Accepted:
  • Published Online:
© 2015 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.067348-0
2015-03-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/3/565.html?itemId=/content/journal/jgv/10.1099/vir.0.067348-0&mimeType=html&fmt=ahah

References

  1. Bennett A. M., Elvin S. J., Wright A. J., Jones S. M., Phillpotts R. J. 2000; An immunological profile of Balb/c mice protected from airborne challenge following vaccination with a live attenuated Venezuelan equine encephalitis virus vaccine. Vaccine 19:337–347 [View Article][PubMed]
     [Google Scholar]
  2. Berglund P., Smerdou C., Fleeton M. N., Tubulekas I., Liljeström P. 1998; Enhancing immune responses using suicidal DNA vaccines. Nat Biotechnol 16:562–565 [View Article][PubMed]
     [Google Scholar]
  3. Frolov I., Hoffman T. A., Prágai B. M., Dryga S. A., Huang H. V., Schlesinger S., Rice C. M. 1996; Alphavirus-based expression vectors: strategies and applications. Proc Natl Acad Sci U S A 93:11371–11377 [View Article][PubMed]
     [Google Scholar]
  4. Guo T. C., Johansson D. X., Haugland O., Liljeström P., Evensen O. 2014; A 6K-deletion variant of salmonid alphavirus is non-viable but can be rescued through RNA recombination. PLoS ONE 9:e100184 [View Article][PubMed]
     [Google Scholar]
  5. Herath T., Costa J., Thompson K., Adams A., Richards R. 2009; Alternative cell line for the isolation of salmonid alphavirus-1. Icel Agric Sci 22:19–27
     [Google Scholar]
  6. Leitner W. W., Ying H., Driver D. A., Dubensky T. W., Restifo N. P. 2000; Enhancement of tumor-specific immune response with plasmid DNA replicon vectors. Cancer Res 60:51–55[PubMed]
     [Google Scholar]
  7. Leitner W. W., Hwang L. N., deVeer M. J., Zhou A., Silverman R. H., Williams B. R., Dubensky T. W., Ying H., Restifo N. P. 2002; Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways. Nat Med 9:33–39 [View Article][PubMed]
     [Google Scholar]
  8. Lundstrom K. 1997; Alphaviruses as expression vectors. Curr Opin Biotechnol 8:578–582 [View Article][PubMed]
     [Google Scholar]
  9. Lundstrom K. 2001; Alphavirus vectors for gene therapy applications. Curr Gene Ther 1:19–29 [View Article][PubMed]
     [Google Scholar]
  10. Lundstrom K. 2005; Biology and application of alphaviruses in gene therapy. Gene Ther 12:Suppl 1S92–S97 [View Article][PubMed]
     [Google Scholar]
  11. Lundstrom K. 2009; Alphaviruses in gene therapy. Viruses 1:13–25 [View Article][PubMed]
     [Google Scholar]
  12. Lundstrom K. 2012; Alphavirus vectors in vaccine development. J Vaccines Vaccin 3:1000139 [View Article]
     [Google Scholar]
  13. Miller J., Ulrich R. 2001; On the analysis of psychometric functions: the Spearman-Kärber method. Percept Psychophys 63:1399–1420 [View Article][PubMed]
     [Google Scholar]
  14. Moriette C., Leberre M., Lamoureux A., Lai T. L., Brémont M. 2006; Recovery of a recombinant salmonid alphavirus fully attenuated and protective for rainbow trout. J Virol 80:4088–4098 [View Article][PubMed]
     [Google Scholar]
  15. Munang’andu H. M., Fredriksen B. N., Mutoloki S., Dalmo R. A., Evensen O. 2013; Antigen dose and humoral immune response correspond with protection for inactivated infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L). Vet Res 44:7 [View Article][PubMed]
     [Google Scholar]
  16. Olsen C. M., Pemula A. K., Braaen S., Sankaran K., Rimstad E. 2013; Salmonid alphavirus replicon is functional in fish, mammalian and insect cells and in vivo in shrimps (Litopenaeus vannamei). Vaccine 31:5672–5679 [View Article][PubMed]
     [Google Scholar]
  17. Phenix K. V., McKenna B., Fitzpatrick R., Vaughan L., Atkins G., Liljestrom P., Todd D. 2000; Cell culture evaluation of the Semliki Forest virus expression system as a novel approach for antigen delivery and expression in fish. Mar Biotechnol (NY) 2:27–37[PubMed]
     [Google Scholar]
  18. Rayner J. O., Dryga S. A., Kamrud K. I. 2002; Alphavirus vectors and vaccination. Rev Med Virol 12:279–296 [View Article][PubMed]
     [Google Scholar]
  19. Riezebos-Brilman A., de Mare A., Bungener L., Huckriede A., Wilschut J., Daemen T. 2006; Recombinant alphaviruses as vectors for anti-tumour and anti-microbial immunotherapy. J Clin Virol 35:233–243 [View Article][PubMed]
     [Google Scholar]
  20. Robert-Guroff M. 2007; Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol 18:546–556 [View Article][PubMed]
     [Google Scholar]
  21. Ryan M. D., Drew J. 1994; Foot-and-mouth disease virus 2A oligopeptide mediated cleavage of an artificial polyprotein. EMBO J 13:928–933[PubMed]
     [Google Scholar]
  22. Salgado-Miranda C., Loza-Rubio E., Rojas-Anaya E., García-Espinosa G. 2013; Viral vaccines for bony fish: past, present and future. Expert Rev Vaccines 12:567–578 [View Article][PubMed]
     [Google Scholar]
  23. Sjöberg E. M., Suomalainen M., Garoff H. 1994; A significantly improved Semliki Forest virus expression system based on translation enhancer segments from the viral capsid gene. Biotechnology (N Y) 12:1127–1131 [View Article][PubMed]
     [Google Scholar]
  24. Strauss J. H., Strauss E. G. 1994; The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 58:491–562[PubMed]
     [Google Scholar]
  25. Wen S., Qi X., Zhou R. 1999; [Study of transcription and cleavage in vitro of HDV with HBV-specific hammerhead ribozyme]. Zhonghua Gan Zang Bing Za Zhi 7:11–12[PubMed]
     [Google Scholar]
  26. Wolf A., Hodneland K., Frost P., Braaen S., Rimstad E. 2013a; A hemagglutinin-esterase-expressing salmonid alphavirus replicon protects Atlantic salmon (Salmo salar) against infectious salmon anemia (ISA). Vaccine 31:661–669 [View Article][PubMed]
     [Google Scholar]
  27. Wolf A., Hodneland K., Frost P., Hoeijmakers M., Rimstad E. 2014; Salmonid alphavirus-based replicon vaccine against infectious salmon anemia (ISA): impact of immunization route and interactions of the replicon vector. Fish Shellfish Immunol 36:383–392 [View Article][PubMed]
     [Google Scholar]
  28. Yamanaka R., Xanthopoulos K. G. 2004; Development of improved Sindbis virus-based DNA expression vector. DNA Cell Biol 23:75–80 [View Article][PubMed]
     [Google Scholar]
  29. Zhou X., Berglund P., Zhao H., Liljeström P., Jondal M. 1995; Generation of cytotoxic and humoral immune responses by nonreplicative recombinant Semliki Forest virus. Proc Natl Acad Sci U S A 92:3009–3013 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.067348-0
Loading
Modification of a salmonid alphavirus replicon vector for enhanced expression of heterologous antigens
J. Gen. Virol. 96, 565 (2015); https://doi.org/10.1099/vir.0.067348-0
/content/journal/jgv/10.1099/vir.0.067348-0
/content/journal/jgv/10.1099/vir.0.067348-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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