Genus: Ranavirus

Genus: Ranavirus

Distinguishing features

Ranaviruses infect one or more species within the classes Reptilia, Amphibia and Osteichthyes and cause systemic infections. Depending upon the virus and the age and health of the host, infections result in a variety of clinical signs such as internal organ hemorrhage, skin sloughing and external petechia. Among currently identified ranaviruses, sequence identity within the major capsid protein is approximately 70% or higher.


Non-enveloped virus particles display a diameter of approximately 150 nm in ultrathin section, whereas enveloped virions measure 160–200 nm in diameter. The capsid has a skewed symmetry with T=133 or 147. The internal lipid bilayer likely contains transmembrane proteins. The nucleoprotein core consists of a long coiled filament 10 nm wide. 

Physicochemical and physical properties

Buoyant density is 1.28 g cm−3 for enveloped particles and 1.32 g cm−3 for non-enveloped particles. Infectivity is rapidly lost at pH 2.0–3.0 and at temperatures above 50°C. Particles are inactivated by treatment with ether, chloroform, sodium deoxychlorate and phospholipase A.

Nucleic acid

The genome is circularly permuted and approximately 30% terminally redundant with a unit size of 104–140 kbp and a G+C content of 49–55% (Table 1.Iridoviridae). With the exception of Singapore grouper iridovirus (SGIV), ranaviruses encode a cytosine DNA methyltransferase which methylates cytosines within the dinucleotide sequence CpG. Although there is one report to the contrary, DNA methylation is likely to occur in the cytoplasm and may protect viral DNA from virus-encoded endonucleolytic attack or prevent recognition by a Toll-like receptor 12-like protein.


Ranavirus genomes contain 26 genes (i.e., open reading frames) that are shared with other members of the family. In addition, there are 27 genes that are found only among members of this genus. Most of the 26 core Iridoviridae genes show relatedness to previously characterized gene products (e.g., DNA polymerase, RNA polymerase II, etc.), whereas the 27 ranavirus-specific genes do not show identity with putative genes outside the genus Ranavirus suggesting that they may have specific roles in host-virus interactions. Ranavirus gene function has been explored through a variety of techniques including ectopic expression of viral proteins, the analysis of conditionally-lethal and knock out mutants, and the knock down of gene expression using either RNA silencing (RNAi) or antisense morpholino oligonucleotides (Jancovich et al., 2015).

Genome organization and replication

The replication cycle of frog virus 3 (FV3) serves as the model for the family (Figure 4.Iridoviridae). The complete genomes of 25 or more ranaviruses have been determined and show marked sequence conservation (Chinchar et al., 2017). Based on whole genome dot plot comparisons there are four genomic phenotypes among ranaviruses (FV3/tiger frog virus /soft-shelled turtle virus -like, Ambystoma tigrinum virus (ATV)/ epizootic haematopoietic necrosis virus (EHNV)-like, SGIV/ grouper iridovirus -like, and common midwife toad virus (CMTV)-like). FV3-, ATV-, and CMTV-like viruses display extensive regions of co-linearity, albeit with evidence of sequence inversions and deletions. In contrast, when compared to the other three, SGIV-like viruses only contain short regions of co-linearity and display extensive re-arrangement of the viral genome. However, despite the marked reshuffling of the genome, SGIV contains 53 ORFs in common with other ranaviruses. The apparent ability of ranaviruses to express conserved, functional gene products despite marked variations in co-linearity suggests that gene expression is not linked to gene order and is consistent with the previously observed high level of genetic recombination.


Viral transmission occurs by feeding (scavenging or cannibalism), parenteral injection, direct contact, or environmental exposure. Ranaviruses are generally promiscuous pathogens and infect multiple species within a taxonomic class as well as members of different classes (Duffus et al., 2015). In vitro, ranaviruses replicate in a wide variety of cultured fish, amphibian, reptilian, avian and mammalian cells at temperatures up to 32°C. Infection causes cytopathic effects culminating in cell death, likely by apoptosis, and the marked inhibition of host DNA, RNA and protein synthesis. In contrast to their marked pathogenicity in vitro, the effect of ranavirus infections in vivo depends on the viral species and the identity, age, and health of the host animal. For example, the largemouth bass virus (LMBV) isolate of Santee-Cooper ranavirus shows evidence of widespread infection in the wild, but is only rarely linked to serious disease. Likewise, FV3 infection leads to death in tadpoles and stressed adults, but often causes only non-apparent subclinical infections in healthy adult frogs and resolves within two weeks. It is likely that environmental stress leading to immune suppression increases the pathogenicity of ranavirus infections. As with infections in vitro, ranavirus infections in vivo are often not limited to a single host species or taxonomic class of animal. For example, EHNV has been reported to infect at least 13 species of fish, and Bohle iridovirus (BIV), a highly virulent pathogen of the burrowing frog Lymnodynastes ornatus, can be experimentally transmitted to fish and reptiles. Therefore, isolation of a ranavirus from a new host species does not necessarily identify a new viral species as the same virus may infect many different hosts. Furthermore, the pathological consequences of ranavirus infections vary markedly. In the most severe cases, ranaviruses such as FV3, ATV, European catfish virus (ECV) and EHNV are associated with life-threatening systemic disease and show marked hemorrhagic involvement of internal organs such as the liver, spleen, kidney and gut (Miller et al., 2015). Although there is a tendency for younger animals to experience more severe disease than older ones, the clinical outcome of infection will vary with the specific virus and host, and with associated environmental stresses.


Ranaviruses such as FV3 are serologically and genetically distinct from members of other genera. However, several piscine, reptilian and amphibian ranavirus isolates show serological cross-reactivity with FV3 (Hedrick et al., 1992). Serological cross-reactivity likely reflects marked amino acid sequence conservation (i.e., >90% identity) within the major capsid protein and other viral proteins.

Derivation of names

Ranavirus species are designated by one of three, albeit imperfect, naming methods: the host species from which the virus was first isolated (Ambystoma tigrinum virus, Common midwife toad virus, Frog virus 3), the typical clinical manifestation of infection (Epizootic hematapoietic necrosis virus), or the geographic site of the first isolate (Santee-Cooper ranavirus).

Species demarcation criteria

Ranavirus species are distinguished by multiple criteria including their members’ amino acid and nucleotide sequence identity, phylogeny, principal host species, genome size, genetic co-linearity, and gene content. Many isolates within the genus show >90% sequence identity within the major capsid protein and other conserved proteins. In view of this, ranavirus isolates are considered members of the same viral species if they share >95% amino acid identity based on a concatentated set of 26 core iridovirid genes, and display phylogenetic relatedness, a co-linear gene arrangement, similar genomic size, and similar G+C content.

Member species

Exemplar isolate of the species
SpeciesVirus nameIsolateAccession numberRefSeq numberAvailable sequenceVirus Abbrev.
Ambystoma tigrinum virusAmbystoma tigrinum virusAY150217NC_005832Complete genomeATV
Common midwife toad viruscommon midwife toad virus-NLPelophylax kl. esculentus/2013/NLKP056312NC_039034Complete genomeCMTV-NL
Common midwife toad viruscommon midwife toad virus -EMesotriton alpesteris/2008/EJQ231222Complete genomeCMTV-E
Common midwife toad virusAndrias davidianus ranavirus1201KC865735Complete genomeADRV
Common midwife toad virusTestudo hermanni ranavirusCH8/96KP266741Complete genomeTHRV
Common midwife toad viruspike-perch iridovirusSLU14001KX574341Complete genomePPIV
Common midwife toad virusPelophylax esculentus virusPEV_DK1MF538627Complete genomePEV_DK1
Common midwife toad virusRana esculenta virusREV 282/102MF538628Complete genomeREV 282/102
Epizootic haematopoietic necrosis virusepizootic haematopoietic necrosis virusAustraliaFJ433873NC_028461Complete genomeEHNV
Epizootic haematopoietic necrosis virusEuropean catfish virus14612/2012KT989885Complete genomeECV
Epizootic haematopoietic necrosis virusEuropean sheatfish virusValdeolmosJQ724856Complete genomeESV
European North Atlantic ranaviruslumpfish ranavirusF24/15MH665358Complete genomeLfRV
Frog virus 3frog virus 3AY548484NC_005946Complete genomeFV3
Frog virus 3frog virus 3spotted salamander isolate - MaineKJ175144Complete genomeSSME
Frog virus 3Rana grylio virusJQ654586Complete genomeRGV
Frog virus 3soft-shelled turtle iridovirusEU627010Complete genomeSSTV
Frog virus 3tiger frog virusAF389451Complete genomeTFV
Frog virus 3German gecko ranavirus2000/99KP266742Complete genomeGGRV
Frog virus 3tortoise ranavirus 1882/96KP266743Complete genomeToRV1
Frog virus 3Bohle iridovirusBIV-ME 93/35KX185156Complete genomeBIV
Frog virus 3zoo ranavirus40414MK227779Complete genomeZRV
Frog virus 3short-finned eel virusANGA 14001KX353311Complete genomeSERV
Frog virus 3cod iridovirusGAM 14001KX574342Complete genomeCoIV
Frog virus 3ranavirus maximusSMA 15001KX574343Complete genomeRmax
Santee-Cooper ranaviruslargemouth bass virusBG/TH/CU3KU507317NC_038508Partial genomeLMBV
Santee-Cooper ranavirusguppy virus 6F93-20 #6FR677325Partial genomeGV6
Santee-Cooper ranavirusdoctor fish virusFR677324Partial genomeDFV
Singapore grouper iridovirusSingapore grouper iridovirusAY521625NC_006549Complete genomeSGIV
Singapore grouper iridovirusGrouper iridovirusAY666015Complete genomeGIV

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

Related, unclassified viruses

This list contains isolates that may represent new species within the genus.

Virus name

Accession number

Virus abbreviation

Genome (bp)



ranavirus maximus






cod iridovirus






short-finned eel virus






Virus names and abbreviations are not official ICTV designations.