Skip to main content
SpringerLink
Log in

Methods for Identifying Virus-Derived Serpins

  • Protocol
  • First Online:
Serpins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1826))

Abstract

The serpin family of serine proteinase inhibitors plays key roles in the maintenance of mammalian homeostasis. Virus-encoded serpins disrupt the balance of mammalian proteases to facilitate virus replication in the infected host. DNA viruses, in particular members of the poxvirus family, have acquired multiple copies of the functional serpins which are essential for viral pathogenesis. Virus-encoded serpins have proven to be very effective inhibitors of host proteases and thus are very attractive candidate molecules as immunomodulatory drugs. With this chapter we explain approaches to identifying immune-modulating viral serpins.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Silverman GA, Bird PI, Carrell RW et al (2001) The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem 276(36):33293–33296. https://doi.org/10.1074/jbc.R100016200

    Article  PubMed  CAS  Google Scholar 

  2. Bratke KA, McLysaght A, Rothenburg S (2013) A survey of host range genes in poxvirus genomes. Infect Genet Evol 14:406–425. https://doi.org/10.1016/j.meegid.2012.12.002

    Article  PubMed  CAS  Google Scholar 

  3. Haller SL, Peng C, McFadden G et al (2014) Poxviruses and the evolution of host range and virulence. Infect Genet Evol 21:15–40. https://doi.org/10.1016/j.meegid.2013.10.014

    Article  PubMed  CAS  Google Scholar 

  4. Ardisson-Araujo DM, Rohrmann GF, Ribeiro BM et al (2015) Functional characterization of hesp018, a baculovirus-encoded serpin gene. J Gen Virol 96(Pt 5):1150–1160. https://doi.org/10.1099/vir.0.000041

    Article  PubMed  CAS  Google Scholar 

  5. Ray CA, Black RA, Kronheim SR et al (1992) Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell 69(4):597–604

    Article  CAS  PubMed  Google Scholar 

  6. Komiyama T, Ray CA, Pickup DJ et al (1994) Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition. J Biol Chem 269(30):19331–19337

    PubMed  CAS  Google Scholar 

  7. Zhou Q, Snipas S, Orth K et al (1997) Target protease specificity of the viral serpin CrmA. Analysis of five caspases. J Biol Chem 272(12):7797–7800

    Article  CAS  PubMed  Google Scholar 

  8. Quan LT, Caputo A, Bleackley RC et al (1995) Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A. J Biol Chem 270(18):10377–10379

    Article  CAS  PubMed  Google Scholar 

  9. Moon KB, Turner PC, Moyer RW (1999) SPI-1-dependent host range of rabbitpox virus and complex formation with cathepsin G is associated with serpin motifs. J Virol 73(11):8999–9010

    PubMed  PubMed Central  CAS  Google Scholar 

  10. Turner PC, Baquero MT, Yuan S et al (2000) The cowpox virus serpin SPI-3 complexes with and inhibits urokinase-type and tissue-type plasminogen activators and plasmin. Virology 272(2):267–280. https://doi.org/10.1006/viro.2000.0377

    Article  PubMed  CAS  Google Scholar 

  11. Lomas DA, Evans DL, Upton C et al (1993) Inhibition of plasmin, urokinase, tissue plasminogen activator, and C1S by a myxoma virus serine proteinase inhibitor. J Biol Chem 268(1):516–521

    PubMed  CAS  Google Scholar 

  12. Nash P, Lucas A, McFadden G (1997) SERP-1, a poxvirus-encoded serpin, is expressed as a secreted glycoprotein that inhibits the inflammatory response to myxoma virus infection. Adv Exp Med Biol 425:195–205

    Article  CAS  PubMed  Google Scholar 

  13. Messud-Petit F, Gelfi J, Delverdier M et al (1998) Serp2, an inhibitor of the interleukin-1beta-converting enzyme, is critical in the pathobiology of myxoma virus. J Virol 72(10):7830–7839

    PubMed  PubMed Central  CAS  Google Scholar 

  14. Nathaniel R, MacNeill AL, Wang YX et al (2004) Cowpox virus CrmA, Myxoma virus SERP2 and baculovirus P35 are not functionally interchangeable caspase inhibitors in poxvirus infections. J Gen Virol 85(Pt 5):1267–1278. https://doi.org/10.1099/vir.0.79905-0

    Article  PubMed  CAS  Google Scholar 

  15. Turner PC, Sancho MC, Thoennes SR et al (1999) Myxoma virus Serp2 is a weak inhibitor of granzyme B and interleukin-1beta-converting enzyme in vitro and unlike CrmA cannot block apoptosis in cowpox virus-infected cells. J Virol 73(8):6394–6404

    PubMed  PubMed Central  CAS  Google Scholar 

  16. Turner PC, Moyer RW (2002) Poxvirus immune modulators: functional insights from animal models. Virus Res 88(1–2):35–53

    Article  CAS  PubMed  Google Scholar 

  17. Upton C, Macen JL, Wishart DS et al (1990) Myxoma virus and malignant rabbit fibroma virus encode a serpin-like protein important for virus virulence. Virology 179(2):618–631

    Article  CAS  PubMed  Google Scholar 

  18. Macen JL, Upton C, Nation N et al (1993) SERP1, a serine proteinase inhibitor encoded by myxoma virus, is a secreted glycoprotein that interferes with inflammation. Virology 195(2):348–363. https://doi.org/10.1006/viro.1993.1385

    Article  PubMed  CAS  Google Scholar 

  19. Lucas A, Liu L, Macen J et al (1996) Virus-encoded serine proteinase inhibitor SERP-1 inhibits atherosclerotic plaque development after balloon angioplasty. Circulation 94(11):2890–2900

    Article  CAS  PubMed  Google Scholar 

  20. Guerin JL, Gelfi J, Camus C et al (2001) Characterization and functional analysis of Serp3: a novel myxoma virus-encoded serpin involved in virulence. J Gen Virol 82(Pt 6):1407–1417. https://doi.org/10.1099/0022-1317-82-6-1407

    Article  PubMed  CAS  Google Scholar 

  21. Brooks MA, Ali AN, Turner PC et al (1995) A rabbitpox virus serpin gene controls host range by inhibiting apoptosis in restrictive cells. J Virol 69(12):7688–7698

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Shisler JL, Isaacs SN, Moss B (1999) Vaccinia virus serpin-1 deletion mutant exhibits a host range defect characterized by low levels of intermediate and late mRNAs. Virology 262(2):298–311. https://doi.org/10.1006/viro.1999.9884

    Article  PubMed  CAS  Google Scholar 

  23. Legrand FA, Verardi PH, Jones LA et al (2004) Induction of potent humoral and cell-mediated immune responses by attenuated vaccinia virus vectors with deleted serpin genes. J Virol 78(6):2770–2779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Guo ZS, Naik A, O'Malley ME et al (2005) The enhanced tumor selectivity of an oncolytic vaccinia lacking the host range and antiapoptosis genes SPI-1 and SPI-2. Cancer Res 65(21):9991–9998. https://doi.org/10.1158/0008-5472.can-05-1630

    Article  PubMed  CAS  Google Scholar 

  25. Smallwood SE, Rahman MM, Smith DW et al. (2010) Myxoma virus: propagation, purification, quantification, and storage. Curr Protoc Microbiol Chapter 14:Unit 14A 11. doi:https://doi.org/10.1002/9780471729259.mc14a01s17

  26. Nash P, Whitty A, Handwerker J et al (1998) Inhibitory specificity of the anti-inflammatory myxoma virus serpin, SERP-1. J Biol Chem 273(33):20982–20991

    Article  CAS  PubMed  Google Scholar 

  27. Lamb SA, Rahman MM, McFadden G (2014) Recombinant myxoma virus lacking all poxvirus ankyrin-repeat proteins stimulates multiple cellular anti-viral pathways and exhibits a severe decrease in virulence. Virology 464–465: 134–145. https://doi.org/10.1016/j.virol.2014.06.021

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Immunotherapy, Vaccines, and Virotherapy, The Biodesign Institute, Arizona State University, Tempe, AZ, USA

    Masmudur M. Rahman

Authors
  1. Masmudur M. Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masmudur M. Rahman .

Editor information

Editors and Affiliations

  1. Biodesign Center for Personalized Diagnostics and Center for Immunotherapy Vaccines and Virotherapy, Arizona State University, Tempe, AZ, USA

    Alexandra Lucas

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Rahman, M.M. (2018). Methods for Identifying Virus-Derived Serpins. In: Lucas, A. (eds) Serpins. Methods in Molecular Biology, vol 1826. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8645-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8645-3_5

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8644-6

  • Online ISBN: 978-1-4939-8645-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation