TY - JOUR
T1 - Genetic adaptation of coxsackievirus B1 during persistent infection in pancreatic cells
AU - Honkimaa, Anni
AU - Kimura, Bryn
AU - Sioofy-Khojine, Amir Babak
AU - Lin, Jake
AU - Laiho, Jutta
AU - Oikarinen, Sami
AU - Hyöty, Heikki
N1 - Funding Information:
Funding: This research was funded by Sigrid Juselius Foundation, Diabetes Research Foundation, Reino Lahtikari Foundation, Novo Nordisk Foundation, Academy of Finland (grant numbers 288671 and 325999) and JDRF. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - Coxsackie B (CVB) viruses have been associated with type 1 diabetes. We have recently observed that CVB1 was linked to the initiation of the autoimmune process leading to type 1 diabetes in Finnish children. Viral persistency in the pancreas is currently considered as one possible mechanism. In the current study persistent infection was established in pancreatic ductal and beta cell lines (PANC-1 and 1.1B4) using four different CVB1 strains, including the prototype strain and three clinical isolates. We sequenced 5′ untranslated region (UTR) and regions coding for structural and non-structural proteins and the second single open reading frame (ORF) protein of all persisting CVB1 strains using next generation sequencing to identify mutations that are common for all of these strains. One mutation, K257R in VP1, was found from all persisting CVB1 strains. The mutations were mainly accumulated in viral structural proteins, especially at BC, DE, EF loops and C-terminus of viral capsid protein 1 (VP1), the puff region of VP2, the knob region of VP3 and infection-enhancing epitope of VP4. This showed that the capsid region of the viruses sustains various changes during persistency some of which could be hallmark(s) of persistency.
AB - Coxsackie B (CVB) viruses have been associated with type 1 diabetes. We have recently observed that CVB1 was linked to the initiation of the autoimmune process leading to type 1 diabetes in Finnish children. Viral persistency in the pancreas is currently considered as one possible mechanism. In the current study persistent infection was established in pancreatic ductal and beta cell lines (PANC-1 and 1.1B4) using four different CVB1 strains, including the prototype strain and three clinical isolates. We sequenced 5′ untranslated region (UTR) and regions coding for structural and non-structural proteins and the second single open reading frame (ORF) protein of all persisting CVB1 strains using next generation sequencing to identify mutations that are common for all of these strains. One mutation, K257R in VP1, was found from all persisting CVB1 strains. The mutations were mainly accumulated in viral structural proteins, especially at BC, DE, EF loops and C-terminus of viral capsid protein 1 (VP1), the puff region of VP2, the knob region of VP3 and infection-enhancing epitope of VP4. This showed that the capsid region of the viruses sustains various changes during persistency some of which could be hallmark(s) of persistency.
KW - Cell models of persistency
KW - Coxsackievirus B1
KW - Enterovirus
KW - Next generation sequencing
KW - Persistent infection
KW - Type 1 diabetes
KW - Virus adaptation
U2 - 10.3390/microorganisms8111790
DO - 10.3390/microorganisms8111790
M3 - Article
AN - SCOPUS:85096557911
SN - 2076-2607
VL - 8
JO - Microorganisms
JF - Microorganisms
IS - 11
M1 - 1790
ER -
