Subfamily: Alphairidovirinae

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 members of the species Singapore grouper iridovirus and Epizootic haematopoietic necrosis virus, but smaller than for members of the other four genera within the family. Megalocytiviruses are distinguished from ranaviruses and lymphocystiviruses by their ability to trigger marked cell enlargement in infected tissues and by 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 and are characterized by the appearance of enlarged cells termed “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 or less and pH11 or higher. 

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 at least eight megalocytiviruses, i.e., infectious spleen and kidney necrosis virus (ISKNV), rock bream iridovirus (RBIV), red seabream iridovirus (RSIV), orange spotted grouper iridovirus (OSGIV), turbot reddish body iridovirus (TRBIV), large yellow croaker iridovirus (LYCIV), giant seaperch iridovirus (GSIV), 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 definitively 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. 


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), Florida pompano (Trachinotus carolinus), 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. 


A monoclonal antibody targeted to red seabream iridovirus detects ISKNV in immunofluorescent antibody assays, but does not recognize fish ranaviruses. Cross-reactivity among megalocytiviruses likely reflects 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. 

Derivation of names

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

Species demarcation criteria

Based on sequence analysis and serological studies, all megalocytiviruses isolated to date appear to be strains of two viral species. Phylogenetic analysis indicates the presence of two clusters, one large cluster 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. 

Related, unclassified viruses

Virus name

Accession number

Virus abbreviation

Genome (bp)



European chub iridovirus






Virus names and abbreviations are not official ICTV designations. 

ND: not determined. 

This table only includes isolates whose genome has been fully sequenced. Phylogenetic analysis suggests that ECIV may represent a novel species within the genus.