Enteroviruses as causative agents in type 1 diabetes: loose ends or lost cause?

• Human β cells express enterovirus entry receptors and can sustain enterovirus replication.
• Acute infection of β cells can lead to extensive islet damage and to fulminant diabetes.
• Persistent infection of β cells could drive islet autoimmunity and the development of T1D.
• The ‘strength’ of the β cell antiviral response may determine whether autoimmunity and T1D develop.

Considerable evidence implies that an enteroviral infection may accelerate or precipitate type 1 diabetes (T1D) in some individuals. However, causality is not proven. We present and critically assess evidence suggesting that islet β cells can become infected with enterovirus, and argue that this may result in one of several consequences. Occasionally, a fully lytic infection may arise and this culminates in fulminant diabetes. Alternatively, an atypical persistent infection develops which can be either benign or promote islet autoimmunity. We propose a model in which the ‘strength’ of the β cell response to the establishment of a persistent enteroviral infection determines the final disease outcome.