Updated: Nov 10, 2020
Coxsackie virus type B4 implicated as a potential course of Diabetes
Enteroviruses have been described to cause diabetes. Although they are known to cause a variety of severe infections this new discovery of their ability to cause diabetes has not been proven in vivo likewise the mechanism of action at the molecular level. Coxsackie virus type B4 (CVB4) has been implicated as a causative agent of diabetes. These findings could pioneer the search for new therapeutic agents. Clinical information has established a connection between SARS-CoV-2 and diabetes therefore this findings are likely to have impact on COVID-19. Researchers suggest that since receptor of SARS-CoV-2 is expressed in the endocrine pancreas, it could operate and lead to diabetes in a similar manner as CVB4, independent of immune reactions.
Coxsackie viruses belong to the Enterovirus family other members include poliovirus and echovirus responsible for mild flu-like illnesses to more debilitating illnesses such as myocarditis, pericarditis, meningitis or pancreatitis. These viruses have been suspected to cause diabetes in humans although the mechanism were unknown. In other to establish this mechanisms, the Reseachers working with animal models engrafted with human pancreatic cells, infected by CVB4 as well as with human and mouse insulin-producing cells, also infected with this virus observed that CVB4 infection induces deregulation of URI, a protein that regulates the normal functions of numerous cellular activities.downregulation of URI triggers a cascade of molecular events leadinf to modification of the genome via hypermethylation and silencinf of Pdx1. This gene is critical for the identity and function of beta cells present in the endocrine pancreas, at the so-called islets of Langerrhans and is responsible for the production and secretion of insulin, a hormone that decreases blood glucose level, Silencing PDX1 results in loss of identity and function of the beta cells, which become more like alpha cells, responsible for increasing blood glucose levels and hence leading to hyperglycemia and subsequent diabetes, independently of any immune reactions. These findings were demonstrated by using various genetically engineered mouse models and genomic studies. They demonstrate that loss of URI in mouse pancreata alters beta cell identity and function, leading to diabetes. Furthermore, diabetic mice that expresses in excess URI in beta cells are more toleranr to glucose.
In several pancreata from diabetic patients that expression of URI, PDX1 and viral partices correlates in beta cells, highlighting a casual link between enterovirus infection and diabetes in humans.
These findings could significantly advance the knowledge about the pathological effects of the virus causinf the current pandemic: In line with this, clinical observations have associated SARS-CoV-2, to diabetes in infected patients. Since the receptor is present in beta cells investigating whether this virus alters URI function and silences the expression of PDX1 to affect beta-cell function, promoting diabetes will be of utmost relevance.
The use of inhibitors against DNA methylase transferase, a protein responsible for the hypermethylation of the genome and silencing of PDX1 in therapeutic strategies would be ideal because this class of inhibitors reinstated PDX1 expression and glucose tolerance in diabetic mice. A number of these inhibitors have been adopted in the treatment of cancer.