1887

Abstract

The devil facial tumour disease (DFTD) has led to a massive decline in the wild Tasmanian devil () population. The disease is caused by two independent devil facial tumours (DFT1 and DFT2). These transmissible cancers have a mortality rate of nearly 100 %. An adenoviral vector-based vaccine has been proposed as a conservation strategy for the Tasmanian devil. This study aimed to determine if a human adenovirus serotype 5 could express functional transgenes in devil cells. As DFT1 cells do not constitutively express major histocompatibility complex class I (MHC-I), we developed a replication-deficient adenoviral vector that encodes devil interferon gamma (IFN-γ) fused to a fluorescent protein reporter. Our results show that adenoviral-expressed IFN-γ was able to stimulate upregulation of beta-2 microglobulin, a component of MHC-I, on DFT1, DFT2 and devil fibroblast cell lines. This work suggests that human adenoviruses can serve as a vaccine platform for devils and potentially other marsupials.

Funding
This study was supported by the:
  • Australian Research Council (Award DP180100520)
    • Principle Award Recipient: AndrewS Flies
  • Australian Research Council (Award DE180100484)
    • Principle Award Recipient: AndrewS Flies
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001812
2022-11-16
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/103/11/jgv001812.html?itemId=/content/journal/jgv/10.1099/jgv.0.001812&mimeType=html&fmt=ahah

References

  1. Pearse A-M, Swift K. Allograft theory: transmission of devil facial-tumour disease. Nature 2006; 439:549 [View Article]
    [Google Scholar]
  2. Pye RJ, Pemberton D, Tovar C, Tubio JMC, Dun KA et al. A second transmissible cancer in Tasmanian devils. Proc Natl Acad Sci USA 2016; 113:374–379 [View Article]
    [Google Scholar]
  3. Lazenby BT, Tobler MW, Brown WE, Hawkins CE, Hocking GJ et al. Density trends and demographic signals uncover the long-term impact of transmissible cancer in Tasmanian devils. J Appl Ecol 2018; 55:1368–1379 [View Article] [PubMed]
    [Google Scholar]
  4. Cunningham CX, Comte S, McCallum H, Hamilton DG, Hamede R et al. Quantifying 25 years of disease-caused declines in Tasmanian devil populations: host density drives spatial pathogen spread. Ecol Lett 2021; 24:958–969 [View Article] [PubMed]
    [Google Scholar]
  5. James S, Jennings G, Kwon YM, Stammnitz M, Fraik A et al. Tracing the rise of malignant cell lines: distribution, epidemiology and evolutionary interactions of two transmissible cancers in Tasmanian devils. Evol Appl 2019; 12:1772–1780 [View Article]
    [Google Scholar]
  6. Pye RJ, Pemberton D, Tovar C, Tubio JMC, Dun KA et al. A second transmissible cancer in Tasmanian devils. Proc Natl Acad Sci U S A 2016; 113:374–379 [View Article] [PubMed]
    [Google Scholar]
  7. Siddle HV, Kreiss A, Tovar C, Yuen CK, Cheng Y et al. Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer. Proc Natl Acad Sci U S A 2013; 110:5103–5108 [View Article] [PubMed]
    [Google Scholar]
  8. Stammnitz MR, Coorens THH, Gori KC, Hayes D, Fu B et al. The origins and vulnerabilities of two transmissible cancers in Tasmanian Devils. Cancer Cell 2018; 33:607–619 [View Article]
    [Google Scholar]
  9. Caldwell A, Coleby R, Tovar C, Stammnitz MR, Kwon YM et al. The newly-arisen Devil facial tumour disease 2 (DFT2) reveals a mechanism for the emergence of a contagious cancer. Elife 2018; 7:1–18 [View Article] [PubMed]
    [Google Scholar]
  10. Tovar C, Pye RJ, Kreiss A, Cheng Y, Brown GK et al. Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils. Sci Rep 2017; 7:1–14 [View Article] [PubMed]
    [Google Scholar]
  11. Pye R, Darby J, Flies AS, Fox S, Carver S et al. Post-release immune responses of Tasmanian devils vaccinated with an experimental devil facial tumour disease vaccine. Wildl Res 2021; 48:701 [View Article]
    [Google Scholar]
  12. Pye R, Patchett A, McLennan E, Thomson R, Carver S et al. Immunization strategies producing a humoral IgG immune response against devil facial tumor disease in the majority of Tasmanian devils destined for wild release. Front Immunol 2018; 9:259 [View Article]
    [Google Scholar]
  13. Pye R, Hamede R, Siddle HV, Caldwell A, Knowles GW et al. Demonstration of immune responses against devil facial tumour disease in wild Tasmanian devils. Biol Lett 2016; 12:20160553 [View Article] [PubMed]
    [Google Scholar]
  14. Wright B, Willet CE, Hamede R, Jones M, Belov K et al. Variants in the host genome may inhibit tumour growth in devil facial tumours: evidence from genome-wide association. Sci Rep 2017; 7:423 [View Article] [PubMed]
    [Google Scholar]
  15. Hamede R, Madsen T, McCallum H, Storfer A, Hohenlohe PA et al. Darwin, the devil, and the management of transmissible cancers. Conserv Biol 2021; 35:748–751 [View Article] [PubMed]
    [Google Scholar]
  16. Margres MJ, Ruiz-Aravena M, Hamede R, Chawla K, Patton AH et al. Spontaneous Tumor Regression in Tasmanian Devils Associated with RASL11A Activation. Genetics 2020; 215:1143–1152 [View Article] [PubMed]
    [Google Scholar]
  17. Flies AS, Flies EJ, Fox S, Gilbert A, Johnson SR et al. An oral bait vaccination approach for the Tasmanian devil facial tumor diseases. Expert Rev Vaccines 2020; 19:1–10 [View Article] [PubMed]
    [Google Scholar]
  18. Müller TF, Schröder R, Wysocki P, Mettenleiter TC, Freuling CM. Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe. PLoS Negl Trop Dis 2015; 9:e0003953 [View Article] [PubMed]
    [Google Scholar]
  19. Gilbert A, Johnson S, Walker N, Wickham C, Beath A et al. Efficacy of Ontario Rabies Vaccine Baits (ONRAB) against rabies infection in raccoons. Vaccine 2018; 36:4919–4926 [View Article] [PubMed]
    [Google Scholar]
  20. Fehlner-Gardiner C, Rudd R, Donovan D, Slate D, Kempf L et al. Comparing ONRAB® AND RABORAL V-RG® oral rabies vaccine field performance in raccoons and striped skunks, New Brunswick, Canada, and Maine, USA. J Wildl Dis 2012; 48:157–167 [View Article] [PubMed]
    [Google Scholar]
  21. Sobey KG, Walpole AA, Rosatte R, Fehlner-Gardiner C, Donovan D et al. An assessment of ONRAB oral rabies vaccine persistence in free-ranging mammal populations in Ontario, Canada. Vaccine 2013; 31:2207–2213 [View Article] [PubMed]
    [Google Scholar]
  22. Liu RY, Zhu YH, Zhou L, Zhao P, Li HL et al. Adenovirus-mediated delivery of interferon-γ gene inhibits the growth of nasopharyngeal carcinoma. J Transl Med 2012; 10:1
    [Google Scholar]
  23. Zhao P, Zhu Y-H, Wu J-X, Liu R-Y, Zhu X-Y et al. Adenovirus-mediated delivery of human IFNgamma gene inhibits prostate cancer growth. Life Sci 2007; 81:695–701 [View Article] [PubMed]
    [Google Scholar]
  24. Dreno B, Urosevic-Maiwald M, Kim Y, Guitart J, Duvic M et al. TG1042 (Adenovirus-interferon-γ) in primary cutaneous B-cell lymphomas: A phase II clinical trial. PLoS One 2014; 9:e83670 [View Article] [PubMed]
    [Google Scholar]
  25. Menezes PQ, Silva TT, Simas FB, Brauner RK, Bandarra P et al. Molecular Detection of Human Adenovirus and Rotavirus in Feces of White-Eared Opossums. Ecohealth 2020; 17:326–332 [View Article] [PubMed]
    [Google Scholar]
  26. Rice M, Wilks CR. Virus and virus-like particles observed in the intestinal contents of the possum, Trichosurus vulpecula. Arch Virol 1996; 141:945–950 [View Article]
    [Google Scholar]
  27. Chong R, Shi M, Grueber CE, Holmes EC, Hogg CJ et al. Fecal viral diversity of captive and wild Tasmanian devils characterized using virion-enriched metagenomics and metatranscriptomics. J Virol 2019; 93:e00205-19 [View Article]
    [Google Scholar]
  28. Harrach B, Tarján ZL, Benkő M. Adenoviruses across the animal kingdom: a walk in the zoo. FEBS Lett 2019; 593:3660–3673 [View Article] [PubMed]
    [Google Scholar]
  29. Thomson D, Meers J, Harrach B. Molecular confirmation of an adenovirus in brushtail possums (Trichosurus vulpecula). Virus Res 2002; 83:189–195 [View Article] [PubMed]
    [Google Scholar]
  30. Pye RJ, Pemberton D, Tovar C, Tubio JMC, Dun KA et al. A second transmissible cancer in Tasmanian devils. Proc Natl Acad Sci USA 2016; 113:374–379 [View Article]
    [Google Scholar]
  31. Binn LN, Marchwicki RH, Stephenson EH. Establishment of a canine cell line: derivation, characterization, and viral spectrum. Am J Vet Res 1980; 41:855–860 [PubMed]
    [Google Scholar]
  32. Flies AS, Darby JM, Lennard PR, Murphy PR, Ong CEB et al. A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers. Sci Adv 2020; 6:eaba5031 [View Article] [PubMed]
    [Google Scholar]
  33. Subach OM, Gundorov IS, Yoshimura M, Subach FV, Zhang J et al. Conversion of red fluorescent protein into a bright blue probe. Chem Biol 2008; 15:1116–1124 [View Article] [PubMed]
    [Google Scholar]
  34. Flies AS, Darby JM, Murphy PR, Pinfold TL, Patchett AL et al. Generation and Testing of Fluorescent Adaptable Simple Theranostic (FAST) Proteins. Bio Protoc 2020; 10:e3696 [View Article] [PubMed]
    [Google Scholar]
  35. He T-C, Zhou S, da Costa LT, Yu J, Kinzler KW et al. A simplified system for generating recombinant adenoviruses. Proc Natl Acad Sci USA 1998; 95:2509–2514 [View Article]
    [Google Scholar]
  36. Liu G-S, Wang J-H, Lee JH, Tsai P-J, Tsai H-E et al. Gene delivery by subconjunctival injection of adenovirus in rats: a study of local distribution, transgene duration and safety. PLoS One 2015; 10:e0143956 [View Article]
    [Google Scholar]
  37. Flies AS, Lyons AB, Corcoran LM, Papenfuss AT, Murphy JM et al. PD-L1 is not constitutively expressed on Tasmanian devil facial tumor cells but is strongly upregulated in response to IFN-γ and can be expressed in the tumor microenvironment. Front Immunol 2016; 7:1–13 [View Article]
    [Google Scholar]
  38. Ong CEB, Lyons AB, Woods GM, Flies AS. Inducible IFN-γ expression for MHC-I upregulation in Devil facial tumor cells. Front Immunol 2018; 9:1–9 [View Article]
    [Google Scholar]
  39. Caldwell A, Coleby R, Tovar C, Stammnitz MR, Kwon YM et al. The newly-arisen Devil facial tumour disease 2 (DFT2) reveals a mechanism for the emergence of a contagious cancer. Elife 2018; 7:e35314 [View Article] [PubMed]
    [Google Scholar]
  40. Ong CEB, Patchett AL, Darby JM, Chen J, Liu G-S et al. NLRC5 regulates expression of MHC-I and provides a target for anti-tumor immunity in transmissible cancers. J Cancer Res Clin Oncol 2021; 147:1973–1991 [View Article] [PubMed]
    [Google Scholar]
  41. Ong CEB, Cheng Y, Siddle HV, Lyons AB, Woods GM et al. Class II transactivator induces expression of MHC-I and MHC-II in transmissible Tasmanian devil facial tumours. Open Biol 2022; 12:220208 [View Article] [PubMed]
    [Google Scholar]
  42. Mena MA, Treynor TP, Mayo SL, Daugherty PS. Blue fluorescent proteins with enhanced brightness and photostability from a structurally targeted library. Nat Biotechnol 2006; 24:1569–1571 [View Article] [PubMed]
    [Google Scholar]
  43. Subach OM, Cranfill PJ, Davidson MW, Verkhusha VV. An enhanced monomeric blue fluorescent protein with the high chemical stability of the chromophore. PLoS One 2011; 6:e28674 [View Article] [PubMed]
    [Google Scholar]
  44. Miyawaki A, Llopis J, Heim R, McCaffery JM, Adams JA et al. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 1997; 388:882–887 [View Article] [PubMed]
    [Google Scholar]
  45. Webster A, Russell WC, Kemp GD. Characterization of the adenovirus proteinase: development and use of a specific peptide assay. J Gen Virol 1989; 70 (Pt 12):3215–3223 [View Article] [PubMed]
    [Google Scholar]
  46. Diouri M, Keyvani-Amineh H, Geoghegan KF, Weber JM. Cleavage efficiency by adenovirus protease is site-dependent. J Biol Chem 1996; 271:32511–32514 [View Article] [PubMed]
    [Google Scholar]
  47. Ugai H, Wang M, Le LP, Matthews DA, Yamamoto M et al. In vitro dynamic visualization analysis of fluorescently labeled minor capsid protein IX and core protein V by simultaneous detection. J Mol Biol 2010; 395:55–78 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001812
Loading
/content/journal/jgv/10.1099/jgv.0.001812
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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