RESUMO
Emergence of 5' terminally deleted coxsackievirus-B RNA forms (CVB-TD) have been associated with the development of human diseases. These CVB-TD RNA forms have been detected in mouse pancreas during acute or persistent experimental infections. To date, the impact of the replication activities of CVB-TD RNA forms on insulin metabolism remains unexplored. Using an immunocompetent mouse model of CVB3/28 infection, acute and persistent infections of major CVB-TD populations were evidenced in the pancreas. The inoculation of mice with homogenized pancreases containing major CVB-TD populations induced acute and chronic pancreatic infections with pancreatitis. In the mouse pancreas, viral capsid protein 1 (VP1) expression colocalized with a decrease in beta cells insulin content. Moreover, in infected mouse pancreases, we showed a decrease in pro-hormone convertase 2 (PCSK2) mRNA, associated with a decrease in insulin plasmatic concentration. Finally, transfection of synthetic CVB-TD50 RNA forms into cultured rodent pancreatic beta cells demonstrated that viral replication with protein synthesis activities decreased the PCSK2 mRNA expression levels, impairing insulin secretion. In conclusion, our results show that the emergence and maintenance of major CVB-TD RNA replicative forms in pancreatic beta cells can play a direct, key role in the pathophysiological mechanisms leading to the development of type 1 diabetes.
Assuntos
Infecções por Coxsackievirus , Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Camundongos , Humanos , Animais , Insulina/metabolismo , RNA/metabolismo , Enterovirus Humano B/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Replicação Viral , Pró-Proteína Convertase 2/metabolismoRESUMO
Group-B Enteroviruses, such as Echoviruses, are a common cause of infections in neonates but fatal myocarditis during Echovirus-induced sepsis have been rarely reported. We report on 2 cases of neonatal Echovirus-related sepsis with myocarditis. Fatal cardiorespiratory failure occurred in both cases. Autopsies and thorough histologic and microbiologic investigations evidenced Echoviruses 5- and 11-induced myocarditis as the cause of death.