Genus: Megalocytivirus

Genus: Megalocytivirus

Distinguishing features

Megalocytiviruses infect multiple species of freshwater and marine fish. Although they are morphologically similar to ranaviruses, the unique component of their genomes is slightly larger (111–112 kbp) than most ranaviruses, except for Singapore grouper iridovirus/ grouper iridovirus and epizootic haematopoietic necrosis virus/ European sheatfish virus, but smaller than for members of the genera Iridovirus and Chloriridovirus and two of the three sequenced lymphocystiviruses. Megalocytiviruses are distinguished from ranaviruses and lymphocystiviruses by the presence of inclusion body-bearing cells and sequence analysis of key viral genes, e.g., ATPase and MCP, for which PCR primers have been developed. Most megalocytiviruses show >94% sequence identity within these genes, whereas sequence identity with ranaviruses and lymphocystiviruses is <50%. Infections in vivo lead to systemic, often life-threatening disease. Infections in vivo are characterized by the appearance of “inclusion body-bearing” cells. Inclusion body-bearing cells are hypertrophied cells containing large foamy or granular basophilic inclusions that distend the cytoplasm and displace the nucleus; they are pathognomonic for infection with megalocytiviruses.



Virions possess icosahedral symmetry and are 140–200 nm in diameter. Virions are inactivated by heat (56°C for 30 min), sodium hypochlorite, UV irradiation, chloroform ether, and by exposure to pH3 and pH11.

Physicochemical and physical properties

Physical properties are likely to be similar to those of other members of the family (see family description)

Nucleic acid

The complete genomes of eight megalocytiviruses, infectious spleen and kidney necrosis virus (ISKNV), rock bream iridovirus, red seabream iridovirus (RSIV), orange spotted grouper iridovirus (OSGIV), turbot reddish body iridovirus (TRBIV), large yellow croaker iridiovirus, giant seaperch iridovirus, and scale drop disease virus (SDDV), have been sequenced. Megalocytivirus particles contain a single, linear dsDNA molecule of 110,104 to 112,636 bp with a G+C content of 53–55%. As with other members of the family, genomic DNA is circularly permuted, terminally redundant and highly methylated.


The protein composition of megalocytiviruses has not been extensively studied. Inspection of viral genomes indicates the presence of between 93 and 135 putative genes.

Genome organization and replication

Replication of megalocytiviruses is assumed to be similar to that of frog virus 3. However, given that there are a number of putative ORFs that are genus-specific, it is also likely that megalocytivirus replication differs in some aspects. 


In immunofluorescent antibody assays, a monoclonal antibody targeted to red seabream iridovirus detects ISKNV, but does not recognize fish ranaviruses. Cross-reactivity among megalocytiviruses is likely to reflect high levels of amino acid identity among viral proteins. Vaccines using inactivated virus or recombinant proteins have been developed, and the former has been licensed for commercial use.


Iridoviruses infecting red seabream, mandarin fish and over 30 other species of marine and freshwater fish have been known since the late 1980s. Isolates from red seabream (RSIV) and mandarin fish (ISKNV) have been studied extensively (Kurita and Nakajima 2012). In vivo, viral infection is characterized by the formation of inclusion body-bearing cells (IBC). IBCs frequently appear in hematopoietic tissues, i.e., spleen and kidney, gills, the digestive tract, and other tissues. Necrotized splenocytes are also observed. Transmission has been demonstrated by feeding, parenteral injection and environmental exposure. Megalocytiviruses naturally infect and cause significant mortality in freshwater and marine fish in aquaculture facilities in China, Japan and South East Asia. Infections have recently been identified in Australia and North America. A partial list of susceptible fish species includes mandarin fish (Siniperca chuatsi), red seabream (Pagrus major), grouper (Epinephelus spp.), yellowtail (Seriola quinqueradiata), striped beakperch (Oplegnathus fasciatus), red drum (Sciaenops ocellata) and African lampeye (Aplocheilichthys normani). The virus grows in several cultured piscine cell lines and causes a characteristic enlargement of infected cells. Outbreaks of disease caused by ISKNV occur only in fish cultured at temperatures >20°C. A vaccine targeted to RSIV has been developed suggesting that infection/immunization is capable of eliciting protective antibodies. 

Species demarcation criteria

Based on sequence analysis and serological studies, all megalocytiviruses isolated to date appear to be strains of the same or a small number of closely-related species. Phylogenetic analysis indicates the presence of two clusters, one composed of RSIV, ISKNV, TRBIV, and other highly similar viruses, and a second , more distant, cluster comprised of a single isolate, SDDV (Figure 6.Iridoviridae). Whether members of the larger cluster represent distinct species, or strains of a single species, remains to be resolved. In general ISKNV-like viruses have been isolated from freshwater fish, whereas RSIV-like viruses infect marine fish.

Member species

SpeciesVirus name(s)Exemplar isolateExemplar accession numberExemplar RefSeq numberAvailable sequenceOther isolatesOther isolate accession numbersVirus abbreviationIsolate abbreviation
Infectious spleen and kidney necrosis virusinfectious spleen and kidney necrosis virusAF371960NC_003494Complete genomeISKNV
Scale drop disease virusscale drop disease virusC4575KR139659NC_027778Partial genomeSDDV

Virus names, the choice of exemplar isolates, and virus abbreviations, are not official ICTV designations.

Derivation of names

Megalocytiviruses have been named after the disease they cause (e.g., Infectious spleen and kidney necrosis virus) or the host species (red seabream iridovirus) they infect.

Related, unclassified viruses

This table only includes isolates whose genome has been fully sequenced.

Virus name

Accession number

Virus abbreviation

Genome (bp)



rock bream iridovirus






red seabream iridovirus






orange spotted grouper iridovirus






turbot reddish body iridovirus






large yellow croaker iridiovirus






giant seaperch iridovirus






scale drop disease virus






Virus names and abbreviations are not official ICTV designations.
ND: not determined.