Understanding the interaction between Betanodavirus and its host for the development of prophylactic measures for viral encephalopathy and retinopathy

Over the last three decades, the causative agent of viral encephalopathy and retinopathy (VER) disease has become a serious problem of marine finfish aquaculture, and more recently the disease has also been associated with farmed freshwater fish. The virus has been classified as a Betanodavirus within the family Nodaviridae, and the fact that Betanodaviruses are known to affect more than 120 different farmed and wild fish and invertebrate species, highlights the risk that Betanodaviruses pose to global aquaculture production. Betanodaviruses have been clustered into four genotypes, based on the RNA sequence of the T4 variable region of their capsid protein, and are named after the fish species from which they were first derived i.e. Striped Jack nervous necrosis virus (SJNNV), Tiger puffer nervous necrosis virus (TPNNV), Barfin flounder nervous necrosis virus (BFNNV) and Red-spotted grouper nervous necrosis virus (RGNNV), while an additional genotype turbot betanodavirus strain (TNV) has also been proposed. However, these genotypes tend to be associated with a particular water temperature range rather than being species-specific. Larvae and juvenile fish are especially susceptible to VER, with up to 100% mortality resulting in these age groups during disease episodes, with vertical transmission of the virus increasing the disease problem in smaller fish. A number of vaccine preparations have been tested in the laboratory and in the field e.g. inactivated virus, recombinant proteins, virus-like particles and DNA based vaccines, and their efficacy, based on relative percentage survival, has ranged from medium to high levels of protection to little or no protection. Ultimately a combination of effective prophylactic measures, including vaccination, is needed to control VER, and should also target larvae and broodstock stages of production to help the industry deal with the problem of vertical transmission. As yet there are no commercial vaccines for VER and the aquaculture industry eagerly awaits such a product. In this review we provide an overview on the current state of knowledge of the disease, the pathogen, and interactions between betanodavirus and its host, to provide a greater understanding of the multiple factors involved in the disease process. Such knowledge is needed to develop effective methods for controlling VER in the field, to protect the various aquaculture species farmed globally from the different Betanodavirus genotypes to which they are susceptible.