''Ranavirus'' is a genus of

viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are found in almo ...

in the family ''

Iridoviridae ''Iridoviridae'' is a family of viruses with double-stranded DNA genomes. Amphibians, fish, and invertebrates such as arthropods serve as natural hosts. There are currently 22 species in this family, divided among two subfamilies and seven genera ...

''. There are six other

genera Genus (; : genera ) is a taxonomic rank above species and below family as used in the biological classification of living and fossil organisms as well as viruses. In binomial nomenclature, the genus name forms the first part of the binomial s ...

virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...

es within the family ''

'', but ''Ranavirus'' is the only one that includes viruses that are infectious to amphibians and reptiles. Additionally, it is one of the three genera within this family which infect

teleost Teleostei (; Ancient Greek, Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts (), is, by far, the largest group of ray-finned fishes (class Actinopterygii), with 96% of all neontology, extant species of f ...

fish A fish (: fish or fishes) is an aquatic animal, aquatic, Anamniotes, anamniotic, gill-bearing vertebrate animal with swimming fish fin, fins and craniate, a hard skull, but lacking limb (anatomy), limbs with digit (anatomy), digits. Fish can ...

es, along with '' Lymphocystivirus'' and '' Megalocytivirus''.

Ecological impact

The Ranaviruses, like the Megalocytiviruses, are an emerging group of closely related

dsDNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

viruses which cause systemic infections in a wide variety of wild and cultured fresh and saltwater fishes. As with Megalocytiviruses, ''Ranavirus'' outbreaks are therefore of considerable economic importance in

aquaculture Aquaculture (less commonly spelled aquiculture), also known as aquafarming, is the controlled cultivation ("farming") of aquatic organisms such as fish, crustaceans, mollusks, algae and other organisms of value such as aquatic plants (e.g. Nelu ...

, as

epizootic In epizoology, an epizootic (or epizoötic, from Greek: ''epi-'' "upon" + ''zoon'' "animal") is a disease event in a nonhuman animal population analogous to an epidemic in humans. An epizootic disease (or ) may occur in a specific locale (an ...

s can result in moderate fish loss or mass mortality events of cultured fishes. Unlike Megalocytiviruses, however, ''Ranavirus'' infections in amphibians have been implicated as a contributing factor in the global decline of amphibian populations. The impact of Ranaviruses on amphibian populations has been compared to the

chytrid Chytridiomycota are a division of zoosporic organisms in the kingdom (biology), kingdom Fungi, informally known as chytrids. The name is derived from the Ancient Greek ('), meaning "little pot", describing the structure containing unreleased zo ...

fungus A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

'' Batrachochytrium dendrobatidis'', the causative agent of

chytridiomycosis Chytridiomycosis ( ) is an infectious disease in amphibians, caused by the chytrid fungi '' Batrachochytrium dendrobatidis'' and '' Batrachochytrium salamandrivorans''. Chytridiomycosis has been linked to dramatic population declines or extinc ...

. In the UK, the severity of disease outbreaks is thought to have increased due to climate change. Recent studies indicate that Ranavirus outbreaks occur globally but are reported unevenly, with (33 out of 68) documented cases being in North America, while only one case was noted in Oceania and two in Africa. This pattern suggests significant geographic gaps in disease surveillance and reporting in various regions.

Etymology

''Rana'' is derived from the

Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...

for "frog", reflecting the first isolation of a ''Ranavirus'' in 1960s from the Northern leopard frog (''

Lithobates pipiens ''Lithobates pipiens''Integrated Taxonomic Information System nternet2012''Lithobates pipiens'' pdated 2012 Sept; cited 2012 Dec 26Available from: www.itis.gov/ formerly ''Rana pipiens'', commonly known as the northern leopard frog, is a species ...

'').

Evolution

The ranaviruses appear to have evolved from a fish virus which subsequently infected amphibians and reptiles.

Hosts

Anuran hosts

* Wood frogs (''Lithobates sylvaticus'') *

American Bullfrog The American bullfrog (''Lithobates catesbeianus''), often simply known as the bullfrog in Canada and the United States, is a large true frog native to eastern North America. It typically inhabits large permanent water bodies such as swamps, po ...

(''Lithobates catesbieanus'') *

Pickerel Frog The pickerel frog (''Lithobates palustris'', formerly ''Rana palustris'') is a small North American frog, characterized by the appearance of seemingly "hand-drawn" squares on its dorsal surface. Distinguishing features The pickerel frog is a me ...

* Craugastor ranoides (''Craugastor ranoides'') – Critically Endangered * Craugastor taurus (''Craugastor taurus'') – Endangered * Agalychnis lemur (''Agalychnis lemur'') – Critically Endangered * Litoria lorica (''Litoria lorica'') – Critically Endangered *

Rana muscosa Rana may refer to: Astronomy * Rana (crater), a crater on Mars * Delta Eridani or Rana, a star Films * Rana (2012 film), an Indian Kannada-language action drama * Rana, a 1998 Telugu-language action film directed by A. Kodandarami Reddy * Rana ...

(''Rana muscosa'') – Endangered *

Rana sierrae Rana may refer to: Astronomy * Rana (crater), a crater on Mars * Delta Eridani or Rana, a star Films * Rana (2012 film), an Indian Kannada-language action drama * Rana, a 1998 Telugu-language action film directed by A. Kodandarami Reddy * R ...

(''Rana sierrae'') – Vulnerable

Urodelan hosts

Reptilian hosts

*Green pythons ('' Chondropython viridis'') *Burmese star tortoises ('' Geochelone platynota'') *Leopard tortoise ('' Geochelone pardalis'') *Gopher tortoises (''

Gopherus polyphemus The gopher tortoise (''Gopherus polyphemus'') is a species of tortoise in the Family (biology), family Testudinidae. The species is native to the southeastern United States. The gopher tortoise is seen as a keystone species because it digs burrow ...

'') *Mountain lizard ('' Lacerta monticola'') *Eastern box turtles ('' Terrapene carolina carolina'') *Florida box turtles ('' Terrapene carolina bauri'') *Western ornate box turtles (''

Terrapene ornata ''Terrapene ornata'' is a species of North American box turtle sometimes referred to as the western box turtle or the ornate box turtle. It is one of two recognized species of box turtle in the United States, having two subspecies. The second rec ...

'') *Spur-thighed tortoises (''

Testudo graeca Greek tortoise (''Testudo graeca''), also known as the spur-thighed tortoise or Moorish tortoise, is a species of tortoise in the family Testudinidae. It is a medium sized herbivorous testudinae, widely distributed in the Mediterranean region. ...

'')Blahak S., Uhlenbrok C. "Ranavirus infections in European terrestrial tortoises in Germany". ''Proceedings of the 1st International Conference on Reptile and Amphibian Medicine''; Munich, Germany. 4–7 March 2010; pp. 17–23 *Hermann's tortoises (''

Testudo hermanni The Hermann's tortoise (''Testudo hermanni)'' is a species of tortoise native to Europe. Etymology The specific epithet, ''hermanni'', honors French naturalist Johann Hermann. Beolens, Bo; Watkins, Michael; Grayson, Michael (2011). ''The Epo ...

'') *Egyptian tortoises ('' Testudo kleinmanni'') *Russian tortoises ('' Testudo horsfieldii'') *Marginated tortoises ('' Testudo marginata'') *Red-eared sliders (''

Trachemys scripta elegans The red-eared slider or red-eared terrapin (''Trachemys scripta elegans'') is a subspecies of the pond slider (''Trachemys scripta''), a semiaquatic turtle belonging to the family Emydidae. Native to the southern United States and extreme north ...

'') *Common snapping turtles (''

Chelydra serpentina The common snapping turtle (''Chelydra serpentina'') is a species of large freshwater turtle in the Family (biology), family Chelydridae. Its natural range extends from southeastern Canada, southwest to the edge of the Rocky Mountains, as far eas ...

'') *Chinese softshell turtles (''

Pelodiscus sinensis The Chinese softshell turtle (''Pelodiscus sinensis'') is a species of softshell turtle that is native to mainland China (Inner Mongolia to Guangxi, including Hong Kong) and Taiwan, with records of escapees—some of which have established Intro ...

'') *Common flat-tail gecko ('' Uroplatus fimbriatus'') *Eastern Fence Lizard (''

Sceloporus undulatus The eastern fence lizard (''Sceloporus undulatus'') is a medium-sized species of lizard in the family Phrynosomatidae. The species is found along forest edges, rock piles, and rotting logs or stumps in the eastern United States. It is sometimes r ...

'')

Taxonomy

The genus contains the following species, listed by scientific name and followed by the exemplar virus of the species: * ''Ranavirus alytes1'', Common midwife toad virus-E * ''Ranavirus ambystoma1'', Ambystoma tigrinum virus * ''Ranavirus epinephelus1'', Singapore grouper iridovirus * ''Ranavirus gadus1'', Cod iridovirus * ''Ranavirus micropterus1'', Largemouth bass virus * ''Ranavirus perca1'', Epizootic haematopoietic necrosis virus * ''Ranavirus rana1'', Frog virus 3 The family ''Iridoviridae'' is divided into seven genera which include '' Chloriridovirus'', '' Iridovirus'', '' Lymphocystivirus'', '' Megalocytivirus'', and ''Ranavirus''. The genus ''Ranavirus '' contains three viruses known to infect amphibians ( Ambystoma tigrinum virus (ATV), Bohle iridovirus (BIV), and frog virus 3).

Structure

Ranaviruses are large

icosahedral In geometry, an icosahedron ( or ) is a polyhedron with 20 faces. The name comes . The plural can be either "icosahedra" () or "icosahedrons". There are infinitely many non- similar shapes of icosahedra, some of them being more symmetrical tha ...

DNA viruses measuring approximately 150 nm in diameter with a large single linear dsDNA

genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...

of roughly 105 kbp which codes for around 100 gene products. The main structural component of the

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or m ...

is the major capsid protein (MCP).

Replication

Ranaviral replication is well studied using ''Frog virus 3'' (FV3). Replication of FV3 occurs between 12 and 32 degrees Celsius. Ranaviruses enter the host cell by

receptor-mediated endocytosis Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, proteins – and in some cases viruses – by the inward budding of the plasma membrane (invagination). This ...

. Viral particles are uncoated and subsequently move into the

cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...

, where viral

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...

begins via a virally encoded

DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create t ...

. Viral DNA then abandons the cell nucleus and begins the second stage of DNA replication in the cytoplasm, ultimately forming DNA concatemers. The viral DNA is then packaged via a headful mechanism into infectious virions. The ''ranavirus'' genome, like other iridoviral genomes is circularly permuted and exhibits

terminally redundant DNA Terminally redundant DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, g ...

. There is evidence that ranavirus infections target macrophages as a mechanism for gaining entry to cells.

DNA repair

Andrias davidianus The Chinese giant salamander (''Andrias davidianus'') is one of the largest salamanders and one of the largest amphibians in the world.homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...

and in DNA double-strand break repair.

Transmission

Transmission of ranaviruses is thought to occur by multiple routes, including contaminated soil, direct contact, waterborne exposure, and ingestion of infected tissues during

predation Predation is a biological interaction in which one organism, the predator, kills and eats another organism, its prey. It is one of a family of common List of feeding behaviours, feeding behaviours that includes parasitism and micropredation ...

necrophagy Scavengers are animals that consume dead organisms that have died from causes other than predation or have been killed by other predators. While scavenging generally refers to carnivores feeding on carrion, it is also a herbivorous feeding beh ...

cannibalism Cannibalism is the act of consuming another individual of the same species as food. Cannibalism is a common ecological interaction in the animal kingdom and has been recorded in more than 1,500 species. Human cannibalism is also well document ...

. Ranaviruses are relatively stable in aquatic environments, persisting several weeks or longer outside a host organism.

Epizoology

Amphibian mass mortality events due to ''Ranavirus'' have been reported in Asia, Europe, North America, and South America. Ranaviruses have been isolated from wild populations of amphibians in Australia, but have not been associated with mass mortality on that continent.

Pathogenesis

Synthesis of viral proteins begins within hours of viral entry with

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

occurring as early as a few hours post infection.

Seasonal disease dynamics

There are several hypotheses for seasonal outbreak patterns observed for Ranavirosis mortality events. Ranaviruses grow ''in vitro'' between 8-30 °C, however for most isolates, warmer temperature result in faster viral replication. A combination of this optimal growth temperature along with shifts in larval amphibian susceptibility result in seasonal outbreak events most often observed during warm summer months. Amphibian mortality events are often observed as larval amphibians reach late Gosner stages approaching

metamorphosis Metamorphosis is a biological process by which an animal physically develops including birth transformation or hatching, involving a conspicuous and relatively abrupt change in the animal's body structure through cell growth and different ...

. As larval amphibians reach metamorphic stages of development, their immune system is reorganized prior to the development of adult tissues. During this time period, amphibians are stressed, and their immune systems are down regulated. This decrease in immune function and warmer environmental temperatures allows for greater viral replication and cellular damage to occur. Across 64 mortality events in the United States 54% were found to occur between June-August.

Environmental persistence

The environmental persistence of Ranaviruses is not understood well, however in realistic environmental conditions the T90 value of an FV3-like virus is 1 day. The duration of persistence is likely affected by temperature and microbial conditions. It is unlikely that ranaviruses persist in the environment outside of host species between outbreak events. Researchers have explored several pathogen reservoirs for the virus which might explain how the virus can persist within an amphibian community. In some amphibian populations, sub-clinically infected individuals may serve as reservoirs for the pathogen. These sub-clinically infected individuals are responsible for reintroduction of the virus to the larval population. With ranaviruses being capable of infected multiple taxa, and with there being differences in susceptibility between taxa, it is likely that sympatric

and

reptile Reptiles, as commonly defined, are a group of tetrapods with an ectothermic metabolism and Amniotic egg, amniotic development. Living traditional reptiles comprise four Order (biology), orders: Testudines, Crocodilia, Squamata, and Rhynchocepha ...

species may serve as reservoirs for virus as well. Interclass transmission has been proven through the use of

mesocosm thumb , Diagram of a small form closed system mesocosm. A mesocosm (''meso-'' or 'medium' and ''-cosm'' 'world') is any outdoor experimental system that examines the natural environment under controlled conditions. In this way mesocosm studi ...

studies.

Gross pathology

Gross lesions associated with ''Ranavirus'' infection include erythema, generalized swelling, hemorrhage, limb swelling, and swollen and friable livers.

References

External links

ICTV Online (10th) Report: Iridoviridae

Global Ranavirus Consortium

Ranaviruses: Lethal Pathogens of Ectothermic Vertebrates
{{Taxonbar, from=Q3418768 Iridoviridae Fish viral diseases Articles containing video clips Virus genera Amphibian diseases Reptile diseases