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Vacuoles in retina of Australian bass larva experimentally infected with NNV.jpg
Vacuoles in retina of Australian bass larva affected with NNV
Virus classification
Group: Group IV ((+)ssRNA)
Family: Nodaviridae
Genus: Betanodavirus
Type Species

Betanodavirus or nervous necrosis virus (NNV) is a viral genus classified in the family Nodaviridae. It contains four recognized species: Barfin flounder nervous necrosis virus (BFNNV), Redspotted grouper nervous necrosis virus(RGNNV), Striped Jack nervous necrosis virus (SJNNV) and Tiger puffer nervous necrosis virus (TPNNV), SJNNV being the type species. There are other 12 tentative species in the genus that haven't been recognized by the ICTV.[1] Betanodaviruses cause a disease in fish called viral nervous necrosis (VNN) or viral encephalopathy and retinopathy (VER).


Betanodaviruses are small single-stranded positive sense RNA viruses, non-enveloped and spherical. The average diameter of the viral capsid is only 37 nm. Its RNA strand is split in two sections RNA1 and RNA2 that together account for 3.5 kbp (approx) that encode 3 genes.[2] Betanodavires can be inactivated by contact with 50ppm of chlorine and iodine for 10 min, 50% and 60% of ethanol and methanol respectively, high alkalinities (pH12), heat treatment (60‹›C for 30 min), UV radiation and ozonation. However they are resistant to Chloroform, ether and formalin.[3]


The virus was reported for the first time during the years 1989-1991 when it was associated with high mortalities in young marine fish and was described initially as a picornavirus-like virus. It was discovered almost simultaneously in Australia, Norway, France and Japan.[2][4][5][6] However, the oldest evidence related to the virus dates back to 1984 in Queensland (Australia) where disease outbreaks with the clinical signs and histopathological lesions corresponding to NNV were referenced for the first time.[7]


Betanodavirus is a genus of viruses, in the family Nodaviridae. Fish serve as natural hosts. There are currently four species in this genus including the type species Striped jack nervous necrosis virus. Diseases associated with this genus include: viral encephalopathy and retinopathy.[8][9]


Group: ssRNA(+)


Crystal structure of a betanodavirus, GNNV[10]


Viruses in Betanodavirus are non-enveloped, with icosahedral geometries, and T=3 symmetry. The diameter is around 30 nm. Genomes are linear and segmented, bipartite, around 21.4kb in length.[8]

The crystal structure of a betanodavirus- T=3 Grouper nervous necrosis virus (GNNV)-like particle has been determined by X-ray crystallography. The virus-like particle contains 180 subunits of the capsid protein, and each capsid protein (CP) shows three major domains: (i) the N-terminal arm, an inter-subunit extension at the inner surface; (ii) the shell domain (S-domain), a jelly-roll structure; and (iii) the protrusion domain (P-domain) formed by three-fold trimeric protrusions. [10]

Genus Structure Symmetry Capsid Genomic arrangement Genomic segmentation
Betanodavirus Icosahedral T=3 Non-enveloped Linear Segmented

Life cycle[edit]

Viral replication is cytoplasmic. Entry into the host cell is achieved by penetration into the host cell. Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription, using the internal initiation model of subgenomic RNA transcription is the method of transcription. Fish serve as the natural host. Transmission routes are passive diffusion and contact.[8]

Genus Host details Tissue tropism Entry details Release details Replication site Assembly site Transmission
Betanodavirus Fish None Unknown Lysis Cytoplasm Cytoplasm Passive diffusion, direct contact


The most recent common ancestor of the four extant genotypes has been dated to ~1300.[11] An early reassortment event appears to have occurred in the early 1980s in Southern Europe.


Betanodaviruses affect teleost fish. A growing number of species are reported susceptible, one of the latest review of the disease (2009) reported more than 40 species, most of them marine. The disease is more likely to occur in larvae or juveniles but it can also affect adults.[12]

Clinical signs and lesions[edit]

Viral nervous necrosis can have a clinical or sub-clinical presentation. Signs include: abnormal behaviour like lethargy, anorexia, spiral swimming; and change in pigmentation. Mortalities of affected populations can be of up to 100%.[3] Microscopical lesions are mostly located in brain, retina and spinal cord where necrosis of the neurons and the presence of round empty spaces called vacoules are commonly associated with the disease.


  1. ^ C.M. Fauquet, M.A.M., J. Manilof, U. Desselberger, L.A. Ball, ed. (2005). Virus Taxonomy (San Diego, California, USA, Elsevier Academic Press)
  2. ^ a b Mori, K.-I., Nakai, T., Muroga, K., Arimoto, M., Mushiake, K., and Furusawa, I. (1992). Properties of a new virus belonging to nodaviridae found in larval striped jack (Pseudocaranx dentex) with nervous necrosis. Virology 187, 368–371.
  3. ^ a b Arimoto, M., Sato, J., Maruyama, K., Mimura, G., and Furusawa, I. (1996). Effect of chemical and physical treatments on the inactivation of striped jack nervous necrosis virus (SJNNV). Aquaculture 143, 15–22.
  4. ^ Glazebrook, J.S., Heasman, M.P., and de Beer, S.W. (1990). Picorna-like viral particles associated with mass mortalities in larval barramundi, Lates calcarifer Bloch. Journal of Fish Diseases 13, 245–249.
  5. ^ Bloch, B., Gravningen, K. & Larsen, J. L. (1991). Encephalomyelitis among turbot associated with picornavirus-like agent. Diseases of Aquatic Organisms 10.
  6. ^ Breuil, G., Bonami, J.R., Pepin, J.F., and Pichot, Y. (1991). Viral infection (picorna-like virus) associated with mass mortalities in hatchery-reared sea-bass (Dicentrarchus labrax) larvae and juveniles. Aquaculture 97, 109–116.
  7. ^ MacKinnon, M.R. (1988). Rearing and growth of larval and juvenile Barramundi (Lates calcarifer)in Queensland. Paper presented at: Management of wild and cultured sea bass/barrumundi (Lates calcarifer) (Darwin, Australian Centre for International Agricultural Research)
  8. ^ a b c "Viral Zone". ExPASy. Retrieved 12 June 2015. 
  9. ^ a b ICTV. "Virus Taxonomy: 2014 Release". Retrieved 12 June 2015. 
  10. ^ a b Chen, N.-C., Yoshimura, M., Guan, H.-H., Wang, T.-Y., Misumi, Y., Lin, C.-C., Chuankhayan, P., Nakagawa, A., Chan, S. I., Tsukihara, T., Chen, T.-Y., Chen, C.-J. (2015). Crystal Structures of a Piscine Betanodavirus: Mechanisms of Capsid Assembly and Viral Infection. PLoS Pathogens 11(10), e1005203.
  11. ^ He M, Teng CB (2014) Divergence and codon usage bias of Betanodavirus, a neurotropic pathogen in fish. Mol Phylogenet Evol pii: S1055-7903(14)00418-7. doi: 10.1016/j.ympev.2014.11.016
  12. ^ Nakai, T., Mori, K., Sugaya, T., Nishioka, T., Mushiake, K., and Yamashita, H. (2009). Current knowledge of viral nervous necrosis (VNN) and its causative betanodaviruses. The Israeli Journal of Aquaculture – Bamidgeh 61, 198–207

External links[edit]