Genetic Susceptibility of the Host in Virus-Induced Diabetes

Abstract

Enteroviruses, especially Coxsackie B viruses, are among the candidate environmental factors causative of type 1 diabetes. Host genetic factors have an impact on the development of virus-induced diabetes (VID). Host background, in terms of whether the host is prone to autoimmunity, should also be considered when analyzing the role of target genes in VID. In this review, we describe the genetic susceptibility of the host based on studies in humans and VID animal models. Understanding the host genetic factors should contribute not only to revealing the mechanisms of VID development, but also in taking measures to prevent VID.

The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α

“…Conspicuously, rare loss-of-function TYK2 promoter mutations (Clin Var, 440728) in the Japanese population predispose to autoantibody-negative T1D and T2D (8). This association has been thought to be linked with increased susceptibility to viral infection(34). However, based on our results, the partial loss of TYK2 expression could lead to a lower β-cell mass as a contributing factor to the increased diabetes risk.…”

Human Cytomegalovirus and Autoimmune Diseases: Where Are We?

“…Type 1 diabetes (T1D) is a chronic disease, characterized by the destruction of pancreatic β-cells, resulting in insulin deficiency. Autoimmune processes triggered by virus infections, combined with genetic susceptibility and environmental factors, have been implicated in the complex pathogenesis of T1D [ 272 , 273 ].…”

SARS-CoV-2 Infection and Pancreatic β Cell Failure

“…Although diabetes is considered a risk factor for severe COVID-19, as described above, SARS-CoV-2 infection may also be a causal factor for diabetes mellitus [ 14 , 15 , 16 ]. Several viruses, including both RNA and deoxyribonucleic acid (DNA) viruses, have been described as potential causal agents for diabetes [ 17 ], such as the enterovirus [ 18 , 19 , 20 ], rotavirus [ 21 ], mumps virus [ 22 ], and cytomegalovirus [ 23 ]. In addition, during the COVID-19 pandemic, a possible association between SARS-CoV-2 infection and new-onset diabetes has been noted [ 11 , 24 , 25 ].…”

“…In addition, during the COVID-19 pandemic, a possible association between SARS-CoV-2 infection and new-onset diabetes has been noted [ 11 , 24 , 25 ]. Viruses may induce pancreatic β-cell death or damage in several ways: induction of direct cell lysis, programed cell death, inflammation (bystander damage or bystander activation), autoimmunity against β cells, dedifferentiation or transdifferentiation, increased insulin resistance in peripheral tissues, and lipotoxicity [ 17 , 26 , 27 , 28 , 29 , 30 , 31 ]. It is well understood that interaction between host factors and viral diabetogenicity is important for the development of diabetes upon virus infection [ 17 , 26 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ].…”

“…Viruses may induce pancreatic β-cell death or damage in several ways: induction of direct cell lysis, programed cell death, inflammation (bystander damage or bystander activation), autoimmunity against β cells, dedifferentiation or transdifferentiation, increased insulin resistance in peripheral tissues, and lipotoxicity [ 17 , 26 , 27 , 28 , 29 , 30 , 31 ]. It is well understood that interaction between host factors and viral diabetogenicity is important for the development of diabetes upon virus infection [ 17 , 26 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. While diabetes has been described, at least in part, as a virus-induced or virus-related disease, the developmental mechanisms of viral infection-induced diabetes are complicated and still unknown [ 26 , 27 ].…”