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Ranaviruses infect one or more species within the classes Reptilia, Amphibia and Osteichthyes and cause systemic infections. Depending upon the age and host species and the specific virus, infected animals display a variety of clinical signs, e.g., internal organ hemorrhage, skin sloughing, external petechial hemorrhages, etc. Among currently identified ranaviruses, sequence similarity 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.
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.
The genome is circularly permuted and approximately 30% terminally redundant. The unit genome size is 104-140 kbp with a G+C content of 49-55% (Table 1.Iridoviridae). With the exception of 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 likely occurs in the cytoplasm and may protect viral DNA from virus-encoded endonucleolytic attack.
Ranaviruses contain 26 genes (i.e., open reading frames) in common 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 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 identify with putative genes outside the genus Ranavirus suggesting that they may play specific roles impacting host-virus interaction. 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 specific genes using either RNA silencing (RNAi) or antisense morpholino oligonucleotides (Jancovich et al., 2015b).
As has been discussed above (Figure 4.Iridoviridae), the replication cycle of FV3 serves as the model for the family. The complete genomes of 25 ranaviruses (Table 1.Iridoviridae) have been sequenced and show marked genetic conservation. Based on whole genome dot plot comparisons there are four genomic phenotypes among the completely sequenced ranaviruses (FV3/TFV/STIV-like, ATV/EHNV-like, SGIV/GIV-like, and 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.
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 MCP and other viral proteins.
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/or 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 SCRV 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 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.
Ranavirus species are distinguished by multiple criteria including amino acid and nucleotide sequence identity/similarity, phylogeny, principal host species, genome size, genetic co-linearity, gene content, and G+C content. Many isolates within the genus show >90% sequence identity/similarity within the major capsid protein and other conserved proteins. In view of this high level of sequence identity, a re-evaluation of the number of ranavirus species is currently under consideration.
Ranavirus species are designated by one of three, albeit imperfect, naming methods: the host species from which the virus was first isolated (e.g., Frog virus 3), the typical clinical manifestation of infection (e.g., Epizootic hematapoietic necrosis virus), or the geographic site of the first isolate (e.g., Bohle iridovirus).
Viral Isolate (Abbreviation)
GenBank Acc. No.
tiger frog virus (TFV)
Rana grylio virus (RGV)
soft-shelled turtle virus (STIV)
German gecko ranavirus (GGRV)
spotted salamander – Maine (SSME)
common midwife toad virus - 2008/E (CMTV/2008/E)
common midwife toad virus – 2013/NL (CMTV/2013/NL)
Testudo hermanni ranavirus (CH8/96)
pike-perch iridovirus (PPIV)
tortoise ranavirus 1 (ToRV1)
Andrias davidianus ranavirus (ADRV)
ranavirus maximus (RMax)
cod iridovirus (CoIV)
short-finned eel virus (SERV)
European sheatfish virus (ESV)
grouper iridovirus (GIV)
Chinese giant salamander iridovirus (CGSIV) – HN1104
These viruses likely represent new species within the genus or strains/isolates of previously identified ranavirus species. Only isolates whose genomes has been completely sequenced are included in this table.
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