IRIDOVIRIDAE

Members of the family Iridoviridae are DNA viruses that are generally 120-200 nm diameter,
but are sometimes even larger (up to 350 nm). Virions exhibit icosahedral symmetry, with a
virus core and outer capsid that are separated by an internal lipid membrane. Virions are
structurally complex and include more than 30 proteins. An envelope is present on virions that
bud from infected cells, but is not necessary for infectivity.

The genomes of iridoviruses consist of a single linear double-stranded DNA molecule that
ranges from 140 to 300 kbp in size, and individual viruses encode between approximately 100
and 200 proteins.

The genome of vertebrate iridoviruses is highly methylated, whereas that of the invertebrate
iridoviruses is not: a virus-encoded methyltransferase present in the iridoviruses of fish, reptiles
and amphibians facilitates methylation of up to 25% of cytosine residues in the genomic DNA,
similar to that in bacteria. This methylation of viral DNA occurs in the cytoplasm during
replication, and its purpose may be to protect the genome from viral endonucleases.

FIVE GENERA
1. Iridovirus – arthropods, scorpions, reptiles, including chelonians (turtles and tortoises),
snakes, and lizards
2. Chloriridovirus – arthropods, lizards, scorpions
3. Ranavirus – reptiles, amphibians, fish
4. Lymphocystis virus – fish; causes tumor-like skin lesions
5. Megalocytivirus - fish

 Megalocytivirus and Ranavirus have emerged as important economically, causing

systemic disease in freshwater and marine environments
TAXONOMY OF THE FAMILY IRIDOVIRIDAE
Genus Virus
Iridovirus Invertebrate iridescent virus 6 (IIV-6) and IIVs-1, -2, -9, -16, -21, -
22, -23, -24, -29, -30, and -31
Chloriridovirus Invertebrate iridescent virus 3
Ranavirus Frog virus 3 (tadpole edema virus, tiger frog virus)
Ambystoma tigrinum virus (regina ranavirus)
Bohle iridovirus
Epizootic hematopoietic necrosis virus
European catfish virus (European sheatfish virus)
Santee-Cooper ranavirus (largemouth bass virus, doctor fish virus,
guppy virus 6) Singapore grouper iridovirus, Grouper iridovirus
Megalocytivirus Infectious spleen and kidney necrosis virus (Red sea bream
iridovirus; African lampeye iridovirus; Orange-spotted grouper
iridovirus; Rock bream iridovirus; Seabass iridovirus, Spotted
knifejaw iridovirus; Taiwan grouper iridovirus; Turbot iridovirus)
Lymphocystivirus Lymphocystis disease virus 1 (LCDV-1 and LCDV-2); Dab LCDV;
Rockfish LCDV
Unclassified White sturgeon iridovirus
Erythrocytic necrosis virus

LYMPHOCYSTIVIRUSES
 Lymphocystis is a benign and self-limiting disease described in a broad range of
freshwater and marine fish species. The condition is caused by a group of iridoviruses
that infect and then transform fibroblasts of the skin and gills and internal connective
tissues, resulting in remarkable hypertrophy of the affected cells

 LYMPHOCYSTS
 These cells appear as raised pearl-like lesions and can be observed readily with
the naked eye.
 Lymphocysts, which may reach 100,000 times the normal cell size, are a result of
virus-mediated arrest of cell division but not cell growth, which leads to the
formation of megalocytes.
 Lymphocysts possess a distinct hyaline-like capsule, an enlarged nucleus, and
bizarre and segmented cytoplasmic inclusions that contain developing virions.
 The characteristic histologic appearance of lymphocysts is athognomonic for
lymphocystis disease, although electron microscopy is often used to confirm the
presence of typical iridovirus virions.
 Infections occur in over 125 species and 34 families of fish from warm,
temperate, and cold, and marine or freshwater environments.
MEGALOCYTIVIRUSES
On microscopic evaluation, numerous large, basophilic, “cytomegalic” cells that have a
subendothelial location are typically present in internal organs such as spleen, kidney, intestine,
eye, pancreas, liver, heart, gill, brain, and intestine; these characteristic cells are reflected in
the genus name for these viruses. The enlarged cells, which may be macrophages, contain
characteristic cytoplasmic inclusions that include the viral assembly site.

Control methods include the use of pathogen-free fish, improved sanitation on fish farms and
husbandry practices that minimize stress (lower fish densities, good water quality, etc.). A
formalin-killed virus vaccine administered by injection has proven efficacious in the control of
the red sea bream iridovirus in Japan. The megalocytiviruses are horizontally transmitted
among fish in the water, and there is no evidence to date for vertical transmission from adults
to progeny.

Gross sign of fish samples. The enlargement of spleen (arrow) and progressive
color change of liver to pale (*) were found in humpback grouper C. altivelis (A
and B) and enlargement of spleen of tiger grouper E. fuscoguttatus (arrow) (C)
and relatively normal size of spleen of E. fuscoguttatus (head arrow) (D)
 H&E stain. Posterior kidney from a variable platyfish (Xiphophorus variatus) with
a megalocytivirus infection. Note large, bluish/purple (basophilic) cells, identified
with arrows, which are filled with viral particles.

RANAVIRUSES
 Frog virus 3
 Infected tadpoles, which are most susceptible, and frogs may exhibit localized
cutaneous hemorrhage and/or ulceration or a more severe systemic disease with
edema, hemorrhage, and necrosis in numerous organs.
 Ambystoma tigrinum virus
 causes mortality in both larval and adult salamanders in western North America
from late summer to early autumn.
 Environmental temperature plays an important role in the pathogenesis of
infection, as most salamanders infected at 26°C survive, whereas at 18°C most
die of the infection
 Bohle iridovirus
 isolated from diseased tadpoles of the ornate burrowing frog (Limnodynastes
ornatus) in Queensland, Australia
 The frogs were suffering from lethargy, skin lesions, and high mortality with
internal lesions that included multifocal necrosis of the liver, kidney, and spleen.
 Epizootic hematopoietic necrosis
 characterized by extensive necrosis of the liver, pancreas, and hematopoietic
cells of the kidney and spleen
 Fingerling and juvenile fish are commonly affected; however, when epizootic
hematopoietic necrosis virus is newly introduced, adults are also susceptible.
 Santee-Cooper ranavirus (largemouth bass virus)
 affects a variety of internal tissues, including the swim bladder, which becomes
reddened and enlarged and contains a yellow exudate. Involvement of the swim
 bladder results in moribund fish that float to the surface, which is often the first
indication of disease in wild fish.
 Ranaviruses are also increasingly recognized as the cause of disease among wild and
captive reptiles including chelonians (turtles and tortoises), lizards, and snakes on
several continents.

(a) Hemorrhages (arrows) and

edema (arrowheads) in a wood
frog (Lithobates sylvaticus)
tadpole experimentally
challenged with an FV3-like
ranavirus. (b) Tongue
hemorrhages (arrows) in a
dusky gopher frog (Lithobates
sevosus) experimentally
challenged with an FV3-like
ranavirus. (c) Intestinal
hemorrhage (arrow) and
congested blood vessels
(arrowhead) in a dusky gopher
frog experimentally challenged
with an FV3-like ranavirus. (d)
Tan friable and hemorrhagic
spleen of a dusky gopher frog

Gross lesions in a red-eared

slider (Trachemys scripta
elegans) experimentally
challenged with an FV3-like
ranavirus. (a) Periocular
swelling. The swelling is
bilateral but more
prominent around the left
eye of this turtle. (b)
Internal soft tissue edema
(arrows) and hemorrhages
(arrowheads). (c) Necrotic
plaques (arrows) on the oral
mucosa. (d) Hemorrhage
(arrows) of the intestinal