Bivalve digestive epithelial virosis (DEV): A cause of disease or a natural process?

Epithelial hyperplasia and sloughing of the digestive gland in bivalve mollusks are a global phenomenon and occur in species of commercial interest and cultural significance to indigenous peoples. Where hemocytosis, hyperplasia, and necrosis of digestive tubule cells have been observed associated with electron-dense uncoated virus-like particles (VLPs) 25-45 nm in diameter, the condition has been named digestive epithelial virosis (DEV). This condition has been associated with mortalities of some bivalve species in New Zealand. Similar digestive gland alterations, but without detection of associated VLPs, have been reported in other bivalve species worldwide and are termed "DEV-like" since no virus link has been demonstrated. It remains unclear if DEV is an infectious condition and whether associated VLPs are the cause, a contributor, or simply associated with the observed condition. It is also unclear whether DEV or DEV-like conditions pose a biosecurity or economic threat, or alternatively, whether they reflect a natural cyclic event that does not require disease management. In this mini-review, we summarize the history of digestive epithelial alteration with VLPs (i.e., DEV) or without observation of VLPs (i.e., DEV-like), and we examine the evidence for and against viral-like particles as the cause of DEV in bivalves. We also explore other viral afflictions of bivalves and non-infectious agents, such as harmful algae and xenotoxins, that could elicit similar tissue alterations. Future recommendations for approaches to identify key risk factors that lead to the development of digestive epithelial alterations such as DEV include histological characterization of the digestive gland of marine mollusks; the use of metagenome analysis to design primers that could be used for detection of VLPs and to study host microbiota; disease challenges demonstrating that DEV causes pathology and the relationship between DEV intensity and morbidity/mortality.