Abstract
While human enteroviruses are generally regarded as a lytic virus, and persistent non-cytolytic enterovirus infection in pancreatic beta cells has been suspected of playing a role in type 1 diabetes pathogenesis. However, it is still unclear how enteroviruses could exit the pancreatic beta cell in a non-lytic manner. This study aimed to investigate the role of beta cell-derived extracellular vesicles (EVs) in the non-lytic enteroviral spread and infection. Size-exclusion chromatography and antibody-based immunoaffinity purification were used to isolate EVs from echovirus 16-infected human beta EndoC-βH1 cells. EVs were then characterized using transmission electron microscopy and Multiplex Bead-Based Flow Cytometry Assay. Virus production and release were quantified by 50% cell culture infectious dose (CCID50) assay and qRT-PCR. Our results showed that EVs from echovirus 16-infected EndoC-βH1 cells harbor infectious viruses and promote their spread during the pre-lytic phase of infection. Furthermore, the EVs-mediated infection was not inhibited by virus-specific neutralizing antibodies. In summary, this study demonstrated that enteroviruses could exit beta cells non-lytically within infectious EVs, thereby thwarting the access of neutralizing antibodies to viral particles. These data suggest that enterovirus transmission through EVs may contribute to viral dissemination and immune evasion in persistently infected beta cells.
Highlights
Human enteroviruses are non-enveloped viruses of 25 to 30 nm in diameter with a single positive-strand RNA genome belonging to the Enterovirus genus of the Picornaviridae family
In addition to acute diseases, human enteroviruses have been associated with chronic conditions, such as type 1 diabetes (T1D) [2]
To investigate whether enteroviruses are released from beta cells in a non-lytic fashion, EndoC-βH1
Summary
Human enteroviruses are non-enveloped viruses of 25 to 30 nm in diameter with a single positive-strand RNA genome belonging to the Enterovirus genus of the Picornaviridae family. The new virions are released from the cell by a lytic mechanism to infect neighboring cells and eventually cause extensive tissue damage [1] Such damage is not typically observed in islets of patients with T1D [6,7,8,9], so that a persistent (non-cytolytic) enteroviral infection capable of evading the host’s immune surveillance, rather than an acute lytic infection, is postulated to stand for the key factor responsible for the progressive loss of insulin-producing pancreatic beta cells [10]. It is still unclear how enteroviruses, typically considered cytolytic viruses, can establish such an infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
