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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 25, 2015; 6(6): 828-839
Published online Jun 25, 2015. doi: 10.4239/wjd.v6.i6.828
Enterovirus and type 1 diabetes: What is the matter?
Carla Sanchez Bergamin, Sergio Atala Dib
Carla Sanchez Bergamin, Sergio Atala Dib, Department of Medicine, São Paulo Federal University, Rua Pedro de Toledo, São Paulo SP-04039001, Brazil
Author contributions: Bergamin CS and Dib SA equally contributed to this paper.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sergio Atala Dib, MD, PhD, Department of Medicine, São Paulo Federal University, Rua Pedro de Toledo, 781 - 12 andar, Vila Clementino, São Paulo SP-04039001, Brazil. sergio.dib@unifesp.br
Telephone: +55-11-55764744 Fax: +55-11-55796636
Received: December 3, 2014
Peer-review started: December 4, 2014
First decision: December 26, 2014
Revised: January 30, 2015
Accepted: April 8, 2015
Article in press: April 9, 2015
Published online: June 25, 2015
Processing time: 199 Days and 5 Hours
Abstract

A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus (T1DM) establishment. Environmental factors may initiate and possibly sustain, accelerate, or retard damage to β-cells. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of human enterovirus in the pathogenesis of T1DM. The genetic risk of T1DM and particular innate and acquired immune responses to enterovirus infection contribute to a tolerance to T1DM-related autoantigens. However, the frequency, mechanisms, and pathways of virally induced autoimmunity and β-cell destruction in T1DM remain to be determined. It is difficult to investigate the role of enterovirus infection in T1DM because of several concomitant mechanisms by which the virus damages pancreatic β-cells, which, consequently, may lead to T1DM establishment. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective.

Keywords: Virus; Enterovirus; Coxsackievirus; Type 1 diabetes mellitus; Auto-immune diabetes; Pathogenesis

Core tip: A complex interaction of genetic and environmental factors can trigger the immune-mediated mechanism responsible for type 1 diabetes mellitus (T1DM) establishment. The role of environmental factors in this process has been exhaustive studied and viruses are among the most probable ones, especially enteroviruses. Improvements in enterovirus detection methods and randomized studies with patient follow-up have confirmed the importance of these viruses in the pathogenesis of T1DM. However the frequency of viruses induces autoimmunity or β-cell destruction and the mechanisms and pathways how they increment the autoimmunity in T1DM still to be determined. Here, we review these mechanisms and all evolution in enterovirus studies and T1DM. Advances in molecular and genomic studies may facilitate the identification of pathways at earlier stages of autoimmunity when preventive and therapeutic approaches may be more effective.