Cargando…

Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Honkimaa, Anni, Kimura, Bryn, Sioofy-Khojine, Amir-Babak, Lin, Jake, Laiho, Jutta, Oikarinen, Sami, Hyöty, Heikki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697981/
https://www.ncbi.nlm.nih.gov/pubmed/33203081
http://dx.doi.org/10.3390/microorganisms8111790
_version_ 1783615724014534656
author Honkimaa, Anni
Kimura, Bryn
Sioofy-Khojine, Amir-Babak
Lin, Jake
Laiho, Jutta
Oikarinen, Sami
Hyöty, Heikki
author_facet Honkimaa, Anni
Kimura, Bryn
Sioofy-Khojine, Amir-Babak
Lin, Jake
Laiho, Jutta
Oikarinen, Sami
Hyöty, Heikki
author_sort Honkimaa, Anni
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7697981
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-76979812020-11-29 Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells Honkimaa, Anni Kimura, Bryn Sioofy-Khojine, Amir-Babak Lin, Jake Laiho, Jutta Oikarinen, Sami Hyöty, Heikki Microorganisms Article 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. MDPI 2020-11-15 /pmc/articles/PMC7697981/ /pubmed/33203081 http://dx.doi.org/10.3390/microorganisms8111790 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Honkimaa, Anni
Kimura, Bryn
Sioofy-Khojine, Amir-Babak
Lin, Jake
Laiho, Jutta
Oikarinen, Sami
Hyöty, Heikki
Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells
title Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells
title_full Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells
title_fullStr Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells
title_full_unstemmed Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells
title_short Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells
title_sort genetic adaptation of coxsackievirus b1 during persistent infection in pancreatic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697981/
https://www.ncbi.nlm.nih.gov/pubmed/33203081
http://dx.doi.org/10.3390/microorganisms8111790
work_keys_str_mv AT honkimaaanni geneticadaptationofcoxsackievirusb1duringpersistentinfectioninpancreaticcells
AT kimurabryn geneticadaptationofcoxsackievirusb1duringpersistentinfectioninpancreaticcells
AT sioofykhojineamirbabak geneticadaptationofcoxsackievirusb1duringpersistentinfectioninpancreaticcells
AT linjake geneticadaptationofcoxsackievirusb1duringpersistentinfectioninpancreaticcells
AT laihojutta geneticadaptationofcoxsackievirusb1duringpersistentinfectioninpancreaticcells
AT oikarinensami geneticadaptationofcoxsackievirusb1duringpersistentinfectioninpancreaticcells
AT hyotyheikki geneticadaptationofcoxsackievirusb1duringpersistentinfectioninpancreaticcells