A human adenovirus encoding IFN-γ can transduce Tasmanian devil facial tumour cells and upregulate MHC-I

Author:

Kayigwe Ahab N.12,M. Darby Jocelyn2,Lyons A. Bruce3ORCID,L. Patchett Amanda2ORCID,Lisowski Leszek45ORCID,Liu Guei-Sheung267ORCID,S. Flies Andrew2ORCID

Affiliation:

1. Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Bibititi and Morogoro Rd Junction, P. O. Box 2958, Dar-es-salaam, Tanzania

2. Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia

3. Tasmanian School of Medicine, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia

4. Military Institute of Medicine, Laboratory of Molecular Oncology and Innovative Therapies, 04-141 Warsaw, Poland

5. Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia

6. Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, 3002, Australia

7. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, 3002, Australia

Abstract

The devil facial tumour disease (DFTD) has led to a massive decline in the wild Tasmanian devil (Sarcophilus harrisii) 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.

Funder

Australian Research Council

Publisher

Microbiology Society

Subject

Virology

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