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

doi:10.1016/j.isci.2021.103653

Persistent coxsackievirus B1 infection triggers extensive changes in the transcriptome of human pancreatic ductal cells

iScience. 2021 Dec 18;25(1):103653. doi: 10.1016/j.isci.2021.103653. eCollection 2022 Jan 21.

Authors

Tanja Buchacher^{1

2}, Anni Honkimaa³, Tommi Välikangas^{1

2}, Niina Lietzén¹, M Karoliina Hirvonen^{1

2}, Jutta E Laiho³, Amir-Babak Sioofy-Khojine³, Eeva-Liisa Eskelinen⁴, Heikki Hyöty^{3

5}, Laura L Elo^{1

2

4}, Riitta Lahesmaa^{1

2}

Affiliations

¹ Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
² InFLAMES Research Flagship Center, University of Turku, Turku, Finland.
³ Faculty of Medicine and Health Technology, Tampere University, Tampere FI-33014, Finland.
⁴ Institute of Biomedicine, University of Turku, Turku FI-20014, Finland.
⁵ Fimlab Laboratories, Pirkanmaa Hospital District, Tampere FI-33520, Finland.

Abstract

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.

Keywords: Cell biology; Transcriptomics; Virology.