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 species of the host, infected animals display a variety of clinical signs such as, internal organ hemorrhage, skin sloughing and external petechial hemorrhages. Among currently identified ranaviruses, sequence identity within the major capsid protein is approximately 70% or higher.

Virion 

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.

Proteins

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., 2015b).

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 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 them (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.

Antigenicity

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.

Biology

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 the species 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.

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 high level of sequence identity, a re-evaluation of the number of ranavirus species is currently underway.

Member species

SpeciesVirus name(s)Exemplar isolateExemplar accession numberExemplar RefSeq numberAvailable sequenceOther isolatesOther isolate accession numbersVirus abbreviationIsolate abbreviation
Ambystoma tigrinum virusAmbystoma tigrinum virusAY150217NC_005832Complete genomeATV
Bohle iridovirusBohle iridovirusME95/35KX185156Complete genomeBIV
Common midwife toad viruscommon midwife toad virusPelophylax kl. esculentus/2013/NLKP056312Complete genomeCMTV
Epizootic haematopoietic necrosis virusepizootic haematopoietic necrosis virusAustraliaFJ433873NC_028461Complete genomeEHNV
European catfish virusEuropean catfish virus13051/2012KT989884Complete genomeECV
Frog virus 3frog virus 3AY548484NC_005946Complete genomeFV3
Santee-Cooper ranaviruslargemouth bass virusBG/TH/CU3KU507317Partial genomeSCRV
Singapore grouper iridovirusSingapore grouper iridovirusAY521625NC_006549Complete genomeSGIV

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

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, European catfish virus, Frog virus 3, and Singapore grouper iridovirus), the typical clinical manifestation of infection (Epizootic hematapoietic necrosis virus), or the geographic site of the first isolate (Bohle iridovirus, Santee-Cooper ranavirus).

Related, unclassified viruses

Only isolates whose genomes has been completely sequenced are included in this table

Virus name

Accession number

Virus abbreviation

Genome (bp)

ORFs

%GC

tiger frog virus

AF389451

TFV

105,057

105

55

Rana grylio virus

JQ654586

RGV

105,791

106

55

soft-shelled turtle virus

EU627010

STIV

105,890

103

55

German gecko ranavirus

KP266742

GGRV

103,681

73

55

spotted salamander – Maine

KJ175144

SSME

105,070

95

55

Testudo hermanni ranavirus

KP266741

CH8/96

105,811

75

55

pike-perch iridovirus

KX574341

PPIV

108,041

109

57

tortoise ranavirus 1)

KP266743

ToRV1

103,876

76

55

Andrias davidianus ranavirus

KC865735

ADRV

106,734

101

55

ranavirus maximus

KX574343

RMax

115,510

100

55

cod iridovirus

KX574342

CoIV

114,865

98

57

short-finned eel virus

KX353311

SERV

126,965

111

56

European sheatfish virus

JQ724856

ESV

127,732

136

54

grouper iridovirus

AY666015

GIV

139,793

139

49

Chinese giant salamander iridovirus– HN1104

KF512820

CGSIV

105,375

111

ND

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