Iridoviruses

Introduction | Taxonomy | Morphology | Genome | Replication | Gene expression | Pathogenesis

Introduction
The family Iridoviridae contains a diverse array of large icosahedral viruses that replicate in the cytoplasm of infected cells. The word Iridoviridae is derived from Iris who was the Greek goddess of the rain ow. This is due to the !rain ow like! iridescence o served in heavily infected insects and pelleted samples of inverte rate iridoviruses.

Larvae of the grass grub Costelytra zealandica displaying blue colouration of the hindgut due to iridovirus infection.

Pellet of purified Tipula iridescent virus This iridescence facilitated the first detection of an iridovirus when "laude Rivers# in March of $%&'# discovered crane fly larvae (Tipula spp) glowing with patches of lue colouration. Iridoviruses have since een isolated from oth inverte rate and non*mammalian verte rate

hosts. + common feature of most of these hosts is the a,uatic or moist environment in which they are found. Iridoviruses have received attention ecause of the pro lems they pose to a,uacultural practices and ecause of their potential use in the iological control of insect pests.

Paracrystalline array of virus particles within infected cell. This array gives rise to the iridescent phenomenon.

Sf21 tissue culture cell showing cytoplasmic localisation of assembling Wiseana iridescent virus particles. N nucleus! "# viroplasmic centre

Ta$onomy
The family Iridoviridae is comprised of four genera# two infecting verte rates and two infecting inverte rates. %enus Iridovirus Chloriridovirus Lymphocystivirus Ranavirus "ernacular name -mall iridescent insect virus 0arge iridescent insect viruses 0ymphocystis disease virus 2rog virus &ost species Inverte rates (mainly insects) Mos,uitos 2ish +mphi ia Type species Chilo iridescent virus (I./) Mos,uito iridescent virus (I.1) 0ymphocystivirus type $ (0"3.*$) 2rog .irus 1 (2.1)

The current I"T. list of recognised Iridoviridae mem ers contains much redundant data. The wide host range displayed y mem ers of this family has resulted in isolates of a single virus species eing descri ed and named more than once ecause of their isolation from different hosts. The host of isolation also confuses taxonomy within the family with recently identified

fish iridoviruses seemingly more related to ranaviruses than to lymphocystiviruses. The pitfalls in iridovirus taxonomy are only 4ust eginning to e addressed using molecular techni,ues.

'epresentation of the homologies between invertebrate iridovirus ma(or capsid genes highlighting the region used for phylogenetic analysis. )ars represent the ma(or capsid proteins from each virus with greyscales ranging from blac* for 1++, homology to the #-I" protein to white for +, homology. 2or example# the P"R amplification and se,uencing of a &55 p fragment of the ma4or capsid protein gene from a num er of inverte rate iridoviruses suggests the genus Iridovirus can e further divided into three groups.

Phylogenetic tree of the genus Iridovirus based on partial .#P se/uence

#ountries of virus isolation "irus TI. (I.$) -I. (I.7) "I. (I./) 9I. (I.%) I.77 %enus Iridovirus Iridovirus Iridovirus Iridovirus Iridovirus &ost crane fly scare gru rice stem orer porina caterpillar grass gru lack fly lack eetle honey ee meal worm corn earworm woodlice #ountry of isolation 6ngland +ustralia 8apan :ew ;ealand :ew ;ealand 9ales -outh +frica India >-+ >-+ >-+

"<I. (I.$/) Iridovirus = I. (I.71) Iridovirus I.7' (+I.) Iridovirus I.7% I.15 I.1$ Iridovirus Iridovirus Iridovirus

+gI. P4I. 0"3.*$

Iridovirus Iridovirus

.elvet ean caterpillar +rgentina 8apanese eetle +<ores 9orld wide

Lymphocystivirus flounder

.orphology

0lectron micrograph of a typical iridovirus Iridoviruses are large ($75 to 155 nm in diameter) non*occluded viruses with icosahedral symmetry. +n iridovirus virion is composed of three concentric domains? an outer proteinaceous capsid# an intermediate lipid mem rane with associated polypeptides# and a central core containing 3:+*protein complexes. -ome# ut not all# viruses possess an outer envelope ac,uired y udding through host mem ranes. 2i rillar structures have also een o served protruding from capsid su units of 0"3.*$# MI.# and "I.# ut not from 2.1. 3epending on the detection method used iridoviruses possess etween 7& to @& structural proteins ranging in molecular weight from $7#555 to $&5#555 k3a. + common feature of all iridoviruses is the presence of a ma4or capsid protein of around &5 k3a that accounts for up to '&A of total virion protein. Prolonged storage of Sericesthis iridescent virus (-I.) in distilled water at 'B" led to the disintegration of virions into triangular# pentagonal and linear fragments consisting of &&# $/# and % su units respectively. These o servations led 9rigley to propose the following $&/7 morphological su unit structure for -I.. 0ater studies on TI. suggested that a structure represented y $'@7 su units may e more appropriate. 0arger iridoviruses reak down into larger ut morphologically similar su units.

Schematic diagram adapted from N.%. 1rigley 1232 (8. Gen. .irol. &C$71*$1')

%enome
Iridoviruses contain a single copy linear ds3:+ genome that ranges in si<e from $&5 to 7D5 k p depending on viral species. The genomes appear uni,ue within the eucaryotic viruses in that they are terminally redundant and cyclically permuted. This structure is a result of the resolution of genome concatamers during 3:+ replication (see replication).

4 simplistic view of terminal redundancy and cyclic permutation. 3uring replication multiple copies of a hypothetical viral genome consisting of $5 genes (+) forms a long concatamer (=). The resolution of this concatamer (") results in packaged 3:+ lengths that contain a complete genome as well as duplicated copies of some genes (terminal redundancy). The ends of each of these packaged 3:+s differs from one virus particle to the next (cyclic permutation). This genomic structure has een found in all iridoviruses so far studied. -u tle variations do occur etween different genera in the cyclic permutation. The packaged 3:+ ends within a population of 2.1 are confined to regions representing 7&A of the genome whereas in "I. and 0"3.*$ the permutation is completely random covering $55A. Plasmid rescue experiments identified six origins of replication in "I.# a feature consistent with cyclic permutation. Three of these origins have een se,uenced and all were predicted to form hairpin structures. The particles of Tipula iridescent virus (TI.) appear uni,ue in that they contain at least two genomic fragments# one of genome length and another of approximately $$ k p. This smaller su genomic fragment hy ridises to defined regions of the genome ut it is not known whether it also contains uni,ue se,uences or what its role is.

'eplication
The replication of iridoviruses comes mainly from studies of 2.1 and this has ecome the model for iridovirus replication. +lthough packaging occurs in the cytoplasm of infected cells# a nuclear stage is also present.

5"6 replication model adapted from '. %oorha 1272 (8. .irol. '1(7)C&$%*&7D) $) .irus particles enter the cell y pinocytosis and uncoating occurs. 7) .iral 3:+ is transported to the cell nucleus where host macromolecular synthesis is rapidly shutdown. Transcription is initiated y virally modified host R:+ polymerase II. 1) Parental 3:+ is used to produce genome and greater than genome length 3:+. This ecomes the template for cytoplasmic replication. ') Progeny 3:+ is transported into the cytoplasm where large concatamers of viral 3:+ are formed y recom ination. Transcription of very late transcripts may also take place in the cytoplasm. &) "oncatamers are resolved into packaged lengths# possi ly y a headful packaging approach. .irions exit the cell y udding or cell lysis.

Possible recombination dependent iridovirus replication. Erigin dependent replication results in the production of duplex 3:+ with single stranded 1F ends (+). These single stranded regions are capa le of recom ination within the same duplex (") or with another 3:+ molecule (=). In this this way these 1F ends serve as primers for further 3:+ replication. The result is a large interlinked and replicating 3:+ concatamer. Modified from G. Mosig $%D@ (+nn. Rev. Genet. 7$C1'@*1@$)

%ene e$pression
-tudies of oth verte rate and inverte rate iridoviruses show transcription occurs in a temporal manner with three stages? immediate*early# delayed*early# and late. There is oth positive induction and some negative feed ack on transcription at each level y translational products of other temporal stages.

5rog virus 6 transcription control model

Pathogenesis
0ittle is known a out the pathogenesis of iridoviruses. The pathogenesis is# however# temperature dependent and iridoviruses are thus confined to poikilothermic hosts. Iridoviruses from the lackfly# Simulium spp.# are found in two states# covert (inapparent) and patent (lethal)# the ratios of each dependent on environmental conditions and host densities. In a lethal infection y insect iridoviruses the fat odies and haemocytes are the initial sites of replication# this leading to a systemic infection. Insects ecome flaccid and iridescent @*$5 days post*infection although death may take 1 weeks or longer. 2.1 is not known to cause disease in naturally occurring frog populations although frog em ryos and larvae die within $& days if inoculated with virus. 2.1 can cause edema of tadpole tails ut has no apparent effect if inoculated into adult frogs.

0"3.*$ causes a nonlethal viral disease of many marine and freshwater fish. + characteristic of the disease is the presence of enormously enlarged host cells (cells can increase in volume y a factor of $5/). Infected fish often have nonmalignant tumour*like growths and rasp erry*like lesions associated with their skin. +lthough 2.1 and 0"3.*$ appear to e non*lethal# high mortality rates amongst various frog and fish populations have een caused y other viruses of the Iridoviridae family.