Megalocytivirus
Encyclopedia
Megalocytivirus is one of five genera
of virus
es within the family Iridoviridae
and one of three genera within this family which infect teleost
fish
es, along with Lymphocystivirus
and Ranavirus
. The megalocytiviruses are an emerging group of closely related dsDNA
viruses which cause systemic infections
in a wide variety of wild and cultured fresh and saltwater fishes. Megalocytivirus outbreaks are of considerable economic importance in aquaculture
, as epizootic
s can result in moderate fish loss or mass mortality events of cultured fishes.
Song, et al. evaluated 48 Asian and Australian megalocytivirus isolates with regard to geographic location and genetic variation in the major capsid protein gene and developed a phylogenetic tree
which divided the 48 isolates into three distinct clusters based on genotype
. One of these clusters (genotype I) is widely distributed among several Asian countries, including 13 isolates from Korea, nine isolates from Japan, one from Thailand, one from China, and one from the South China Sea. In contrast, the other two genotypes had a smaller host range and were locally distributed. Genotype II megalocytiviruses infected freshwater fishes from Southeast Asia and Australia, whereas genotype III megalocytiviruses infected primarily flatfish in China and Korea.
.
Megaloviruses are assumed to replicate in the same fashion as other Iridoviruses, and attach to the host cell and enter by receptor-mediated endocytosis
. Uncoated viral particles subsequently translocate to the host cell nucleus
, where a virally encoded DNA polymerase
facilitates DNA replication
. Viral DNA then leaves the nucleus of the host cell and a second stage of DNA replication occurs in the cytoplasm, forming DNA concatemers. A headful mechanism is utilized to package the concatameric viral DNA into virions formed at cytoplasmic virus assembly sites. Iridoviral DNA, unlike other DNA viruses infecting eukaryotic cells, is circularly permuted and exhibits terminal redundancies
.
of megalocytiviruses because of the economic importance of commercial fisheries
and aquaculture operations. Interestingly, iridoviral epizootics do not correlate well with commercial food fish trade routes, with the notable exception of larval fish trade in Korea and Japan.
A second potential mechanism for accidental movement of infected fish is the international trade in ornamental or aquarium fishes, which includes the global trade of approximately 5000 freshwater and 1450 saltwater fishes. Each year over 1 billion individual fish are shipped among more than 100 nations, creating a serious concern for the spread of megalocytiviruses as well as other important fish pathogen
s. There is already substantial evidence of this problem: megalocytiviruses which are genetically identical or exremely similar to ISKNV have been isolated from ornamental fishes (gourami
s) that were being traded internationally. Furthermore, an Australian outbreak of megalocytivirus among farmed Murray cod
(Maccullochella peelii) was linked to imported gouramis in pet shops. In addition, a 2008 study reported 10 aquarium fish species that tested positive for ISKNV in Korea.
, uncoordinated swimming
, lethargy, coelomic distention, darkening skin color, petechia
e, fin erosion, and death
.
Large conspicuous hypertrophied
cells, for which the genus is named, are evident in multiple organs when diseased tissues are examined by histopathology
; these distinctive cells are commonly observed in the kidney
, spleen
and gastrointestinal tract
and less commonly seen in the liver
, gills, heart
, and connective tissue
. The hypertrophied cells are frequently perivascular in distribution and are greatly enlarged due to large granular to foamy basophilic
cytoplasm
ic inclusion bodies
. If the distended cells occlude the vasculature
, focal areas of ischemic
necrosis
may be evident within various organs. It has been suggested by some researchers that the hypertrophied cells are some type of leukocyte, which is consistent with their tissue distribution.
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
of virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es within the family Iridoviridae
Iridoviridae
Iridoviridae are a family of viruses with double stranded DNA genomes. The name is derived from Iris the Greek goddess of the rainbow. This name was chosen because of the "rainbow like" iridescence observed in heavily infected insects and pelleted samples of invertebrate iridoviruses.-Taxonomy:The...
and one of three genera within this family which infect teleost
Teleostei
Teleostei is one of three infraclasses in class Actinopterygii, the ray-finned fishes. This diverse group, which arose in the Triassic period, includes 20,000 extant species in about 40 orders; most living fishes are members of this group...
fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
es, along with Lymphocystivirus
Lymphocystivirus
Lymphocystivirus is one of five genera of viruses within the viral family Iridoviridae, and one of three genera within this family which infect teleost fishes, along with Megalocytivirus and Ranavirus...
and Ranavirus
Ranavirus
Ranavirus is one of five genera of viruses within the family Iridoviridae, one of the five families of nucleocytoplasmic large DNA viruses . Ranavirus is the only genus within Iridoviridae that includes viruses that are infectious to amphibians and reptiles, and one of only three genera within...
. The megalocytiviruses are an emerging group of closely related dsDNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
viruses which cause systemic infections
Systemic disease
Life-threatening disease redirects here.A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole. Although most medical conditions will eventually involve multiple organs in advanced stage Life-threatening disease redirects here.A systemic disease is one...
in a wide variety of wild and cultured fresh and saltwater fishes. Megalocytivirus outbreaks are of considerable economic importance in aquaculture
Aquaculture
Aquaculture, also known as aquafarming, is the farming of aquatic organisms such as fish, crustaceans, molluscs and aquatic plants. Aquaculture involves cultivating freshwater and saltwater populations under controlled conditions, and can be contrasted with commercial fishing, which is the...
, as epizootic
Epizootic
In epizoology, an epizootic is a disease that appears as new cases in a given animal population, during a given period, at a rate that substantially exceeds what is "expected" based on recent experience . Epidemic is the analogous term applied to human populations...
s can result in moderate fish loss or mass mortality events of cultured fishes.
Taxonomy
The family Iridoviridae is divided into five genera which include Chloriridovirus, Iridovirus, Lymphocystivirus, Megalocytivirus, and Ranavirus. Megalocytivirus is the most recently added genus. Megalocytivirus isolates exhibit relatively few genetic differences and have been divided into three major groups based on genetic sequence data; these groups are represented by infectious spleen and kidney necrosis virus (ISKNV), red sea bream iridovirus (RSIV), and turbot reddish body iridovirus (TRBIV). RSIV and ISKNV are the best known of the megalocytiviruses.Song, et al. evaluated 48 Asian and Australian megalocytivirus isolates with regard to geographic location and genetic variation in the major capsid protein gene and developed a phylogenetic tree
Phylogenetic tree
A phylogenetic tree or evolutionary tree is a branching diagram or "tree" showing the inferred evolutionary relationships among various biological species or other entities based upon similarities and differences in their physical and/or genetic characteristics...
which divided the 48 isolates into three distinct clusters based on genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
. One of these clusters (genotype I) is widely distributed among several Asian countries, including 13 isolates from Korea, nine isolates from Japan, one from Thailand, one from China, and one from the South China Sea. In contrast, the other two genotypes had a smaller host range and were locally distributed. Genotype II megalocytiviruses infected freshwater fishes from Southeast Asia and Australia, whereas genotype III megalocytiviruses infected primarily flatfish in China and Korea.
Structure and replication
Megalocytiviruses are large icosahedral DNA viruses measuring 150-250 nm in diameter with a large single linear dsDNA genomeGenome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
.
Megaloviruses are assumed to replicate in the same fashion as other Iridoviruses, and attach to the host cell and enter by receptor-mediated endocytosis
Receptor-mediated endocytosis
Receptor-mediated endocytosis , also called clathrin-dependent endocytosis, is a process by which cells internalize molecules by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized.-Process:After the binding of a...
. Uncoated viral particles subsequently translocate to the host cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, where a virally encoded DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
facilitates DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
. Viral DNA then leaves the nucleus of the host cell and a second stage of DNA replication occurs in the cytoplasm, forming DNA concatemers. A headful mechanism is utilized to package the concatameric viral DNA into virions formed at cytoplasmic virus assembly sites. Iridoviral DNA, unlike other DNA viruses infecting eukaryotic cells, is circularly permuted and exhibits terminal redundancies
Terminally redundant DNA
Terminally redundant DNA is DNA that contains repeated sequences at each end called terminal repeats. These ends are used to join the ends of the linear DNA to form a cyclic DNA....
.
Transmission and epizoology
Transmission of megalocytivirus is believed to occur when a naive fish ingests tissues from infected fish or via contaminated water. Considerable effort has been expended to understand the transmission and epizoologyEpizoology
Epizoology, or veterinary epidemiology, is the study of disease patterns within animal populations. See epidemiology....
of megalocytiviruses because of the economic importance of commercial fisheries
Fishery
Generally, a fishery is an entity engaged in raising or harvesting fish which is determined by some authority to be a fishery. According to the FAO, a fishery is typically defined in terms of the "people involved, species or type of fish, area of water or seabed, method of fishing, class of boats,...
and aquaculture operations. Interestingly, iridoviral epizootics do not correlate well with commercial food fish trade routes, with the notable exception of larval fish trade in Korea and Japan.
A second potential mechanism for accidental movement of infected fish is the international trade in ornamental or aquarium fishes, which includes the global trade of approximately 5000 freshwater and 1450 saltwater fishes. Each year over 1 billion individual fish are shipped among more than 100 nations, creating a serious concern for the spread of megalocytiviruses as well as other important fish pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s. There is already substantial evidence of this problem: megalocytiviruses which are genetically identical or exremely similar to ISKNV have been isolated from ornamental fishes (gourami
Gourami
Gouramis are a family, Osphronemidae, of freshwater perciform fishes. The fish are native to Asia, from Pakistan and India to the Malay Archipelago and north-easterly towards Korea. The name "gourami" is also used for fish of the families Helostomatidae and Anabantidae. "Gouramis" is an example of...
s) that were being traded internationally. Furthermore, an Australian outbreak of megalocytivirus among farmed Murray cod
Murray Cod
The Murray cod is a large Australian predatory freshwater fish of the Maccullochella genus and the Percichthyidae family. Although the species is a called cod in the vernacular, it is not related to the northern hemisphere marine cod species...
(Maccullochella peelii) was linked to imported gouramis in pet shops. In addition, a 2008 study reported 10 aquarium fish species that tested positive for ISKNV in Korea.
Pathogenesis
As megalocytiviruses have only been recently identified and described, the pathogenesis of megalocytivirus infection is relatively poorly understood. Clinical signs associated with infection are nonspecific and may include appetite lossAnorexia (symptom)
Anorexia is the decreased sensation of appetite...
, uncoordinated swimming
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, lethargy, coelomic distention, darkening skin color, petechia
Petechia
A petechia is a small red or purple spot on the body, caused by a minor hemorrhage ."Petechiae" refers to one of the three major classes of purpuric skin conditions. Purpuric eruptions are classified by size into three broad categories...
e, fin erosion, and death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
.
Large conspicuous hypertrophied
Hypertrophy
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It should be distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number...
cells, for which the genus is named, are evident in multiple organs when diseased tissues are examined by histopathology
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
; these distinctive cells are commonly observed in the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
and gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
and less commonly seen in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, gills, heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, and connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
. The hypertrophied cells are frequently perivascular in distribution and are greatly enlarged due to large granular to foamy basophilic
Basophilic
Basophilic is a technical term used by histologists. It describes the microscopic appearance of cells and tissues, as seen down the microscope, after a histological section has been stained with a basic dye. The most common such dye is haematoxylin....
cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic inclusion bodies
Inclusion bodies
Inclusion bodies are nuclear or cytoplasmic aggregates of stainable substances, usually proteins. They typically represent sites of viral multiplication in a bacterium or a eukaryotic cell and usually consist of viral capsid proteins...
. If the distended cells occlude the vasculature
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
, focal areas of ischemic
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
may be evident within various organs. It has been suggested by some researchers that the hypertrophied cells are some type of leukocyte, which is consistent with their tissue distribution.