Persistent coxsackievirus B1 infection triggers extensive changes in the transcriptome of human pancreatic ductal cells
Tanja Buchacher,
Anni Honkimaa,
Tommi Välikangas,
Niina Lietzén,
M. Karoliina Hirvonen,
Jutta E. Laiho,
Amir-Babak Sioofy-Khojine,
Eeva-Liisa Eskelinen,
Heikki Hyöty,
Laura L. Elo,
Riitta Lahesmaa
Affiliations
Tanja Buchacher
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland
Anni Honkimaa
Faculty of Medicine and Health Technology, Tampere University, Tampere FI-33014, Finland
Tommi Välikangas
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland
Niina Lietzén
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland
M. Karoliina Hirvonen
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland
Jutta E. Laiho
Faculty of Medicine and Health Technology, Tampere University, Tampere FI-33014, Finland
Amir-Babak Sioofy-Khojine
Faculty of Medicine and Health Technology, Tampere University, Tampere FI-33014, Finland
Eeva-Liisa Eskelinen
Institute of Biomedicine, University of Turku, Turku FI-20014, Finland
Heikki Hyöty
Faculty of Medicine and Health Technology, Tampere University, Tampere FI-33014, Finland; Fimlab Laboratories, Pirkanmaa Hospital District, Tampere FI-33520, Finland
Laura L. Elo
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland; Institute of Biomedicine, University of Turku, Turku FI-20014, Finland
Riitta Lahesmaa
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland; Corresponding author
Summary: Enteroviruses, particularly the group B coxsackieviruses (CVBs), have been associated with the development of type 1 diabetes. Several CVB serotypes establish chronic infections in human cells in vivo and in vitro. However, the mechanisms leading to enterovirus persistency and, possibly, beta cell autoimmunity are not fully understood. We established a carrier-state-type persistent infection model in human pancreatic cell line PANC-1 using two distinct CVB1 strains and profiled the infection-induced changes in cellular transcriptome. In the current study, we observed clear changes in the gene expression of factors associated with the pancreatic microenvironment, the secretory pathway, and lysosomal biogenesis during persistent CVB1 infections. Moreover, we found that the antiviral response pathways were activated differently by the two CVB1 strains. Overall, our study reveals extensive transcriptional responses in persistently CVB1-infected pancreatic cells with strong opposite but also common changes between the two strains.
