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''Lymphocystivirus'' is a genus of
virus 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. Since Dmitri Ivanovsky's 1 ...
es, 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 gener ...
''. Fish serve as natural hosts. There are four species in this genus. Diseases associated with this genus include: tumor-like growths on the skin.


Hosts

''Lymphocystivirus'' is one of six
genera Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nomenclat ...
of
virus 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. Since Dmitri Ivanovsky's 1 ...
es within the viral 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 gener ...
'', and one of three genera within this family which infect
teleost Teleostei (; Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts ), is, by far, the largest infraclass in the class Actinopterygii, the ray-finned fishes, containing 96% of all extant species of fish. Tel ...
fish Fish are aquatic, craniate, gill-bearing 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. Approximately 95% of li ...
es, along with ''
Megalocytivirus ''Megalocytivirus'' is a genus of viruses in the family ''Iridoviridae'' and one of three genera within this family which infect teleost fishes, along with ''Lymphocystivirus'' and ''Ranavirus''. Megalocytiviruses are an emerging group of closely ...
'' and ''
Ranavirus ''Ranavirus'' is a genus of viruses, in the family ''Iridoviridae''. There are six other genus, genera of viruses within the family ''Iridoviridae'', but ''Ranavirus'' is the only one that includes viruses that are infectious to amphibians and ...
''. Lymphocystiviruses infect more than 140
freshwater Fresh water or freshwater is any naturally occurring liquid or frozen water containing low concentrations of dissolved salts and other total dissolved solids. Although the term specifically excludes seawater and brackish water, it does include ...
and
marine Marine is an adjective meaning of or pertaining to the sea or ocean. Marine or marines may refer to: Ocean * Maritime (disambiguation) * Marine art * Marine biology * Marine debris * Marine habitats * Marine life * Marine pollution Military * ...
species, spanning at least 42 host families worldwide, causing the chronic, self-limiting clinical disease,
lymphocystis Lymphocystis is a common viral disease of freshwater and saltwater fish. The virus that causes this disease belongs to the genus ''Lymphocystivirus'' of the family Iridoviridae. Aquarists often come across this virus when their fish are stressed ...
. While lymphocystis does not cause mass mortality events like megalocytiviruses and ranaviruses, fish with lymphocystis exhibit grossly visible papilloma-like skin lesions which substantially reduce their commercial value. No vaccines are currently available for lymphocystis viruses.


Taxonomy

The genus contains the following species: * ''
Lymphocystis disease virus 1 ''Lymphocystivirus'' is a genus of viruses, in the family ''Iridoviridae''. Fish serve as natural hosts. There are four species in this genus. Diseases associated with this genus include: tumor-like growths on the skin. Hosts ''Lymphocystivirus ...
'' * ''
Lymphocystis disease virus 2 Lymphocystis is a common viral disease of freshwater and saltwater fish. The virus that causes this disease belongs to the genus ''Lymphocystivirus'' of the family Iridoviridae. Aquarists often come across this virus when their fish are stress ...
'' * ''
Lymphocystis disease virus 3 Lymphocystis is a common viral disease of freshwater and saltwater fish. The virus that causes this disease belongs to the genus ''Lymphocystivirus'' of the family Iridoviridae. Aquarists often come across this virus when their fish are stress ...
'' * ''
Lymphocystis disease virus 4 Lymphocystis is a common viral disease of freshwater and saltwater fish. The virus that causes this disease belongs to the genus ''Lymphocystivirus'' of the family Iridoviridae. Aquarists often come across this virus when their fish are stress ...
''


LCDV genome

Lymphocystiviruses are Group I viruses with a dsDNA
genome In the fields of molecular biology and genetics, 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 ge ...
. The LCDV-1 genome is approximately 102.7 kilobase pairs (kbp) in length, with 195 potential
open reading frames In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
(ORF), and codes for two DNA-dependent
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...
subunits, a
DNA methyltransferase In biochemistry, the DNA methyltransferase (DNA MTase, DNMT) family of enzymes catalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions. All the known DNA methyltransferases use S-adenosyl m ...
, a
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 ...
, a guanosine triphosphate phosphohydrolase (
GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a pro ...
), a
helicase Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...
,
protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...
s, a ribonucleoside diphosphate reductase, and zinc-finger proteins, among others. The LCDV-2 genome is similar to that of LCDV-1 but is slightly smaller, approximately 98 kilobase pairs (kbp) in length.


Structure

Viruses in the genus ''Lymphocystivirus'' are enveloped, with icosahedral and polyhedral geometries, and T=189-217 symmetry. The diameter is around 120-350 nm. Genomes are linear, around 100kb in length.


Life cycle

Lymphocystiviruses attach to the host cell and enter 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). Thi ...
similar to other iridoviruses.Eaton HE, Ring BA, Brunetti CR (2010). "The genomic diversity and phylogenetic relationship in the family ''Iridoviridae''." ''Viruses.'' 2:1458-1475. http://www.mdpi.com/1999-4915/2/7/1458/pdf Viral particles are uncoated and move to the
nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...
of the cell, where
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 living organisms acting as the most essential part for biological inheritanc ...
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 ...
. Viral DNA then moves to the cytoplasm for the second stage of DNA replication, which results in the formation of DNA
concatemers A concatemer is a long continuous DNA molecule that contains multiple copies of the same DNA sequence linked in series. These polymeric molecules are usually copies of an entire genome linked end to end and separated by ''cos'' sites (a protein bi ...
. The concatameric viral DNA is subsequently packaged via a headful mechanism into virions.Chinchar VG, Essbauer S, He JG, Hyatt A, Miyazaki T, Seligy V, Williams T (2005). "Family ''Iridoviridae'' 145-162. ''In'' Fauquet CM, Mayo MA, Maniloff J, Desselburger U, Ball LA (eds). ''Virus Taxonomy, Eighth report of the International Committee on Taxonomy of Viruses.'' Academic Press, San Diego, USA. The lymphocystis viral genome is circularly permuted with
terminally redundant DNA Terminally redundant DNA is DNA that contains repeated sequences at each end called terminal repeat A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on eithe ...
. DNA-templated transcription is the method of transcription. Fish serve as the natural host.


Pathogenesis

Lymphocystis disease is a chronic disease that rarely causes mortality. Infection causes transformation and hypertrophy (approximately 1000x) of cells in the dermis, forming grossly visible lymphocystis nodules, as well as transformation and hypertrophy in cells of the connective tissues of various internal organs.
Fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...
and
osteoblasts Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
are specifically targeted by the virus. Lymphocystis viruses are not easily grown in
cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...
, placing limitations on ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
'' molecular pathogenesis experiments.


Diagnostic pathology

As lymphocystis viruses are not easily grown in cell culture,
diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
is based on
clinical signs Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
,
gross pathology Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of ...
,
histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...
,
serology Serology is the scientific study of Serum (blood), serum and other body fluids. In practice, the term usually refers to the medical diagnosis, diagnostic identification of Antibody, antibodies in the serum. Such antibodies are typically formed in r ...
, and/or
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
(PCR)-based
molecular A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
assay An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a ...
s.


Gross pathology

The pathology of lymphocystis consists of papilloma-like skin lesions composed of greatly hypertrophied infected host cells embedded in extracellular matrix, sometimes called lymphocystis tumor cells, which are grossly evident as white spots on the skin and fins of infected fish. These lesions proliferate as epithelial tumors in some cases.


Histopathology

In a recent comparison of lymphocystis histopathology of four unrelated marine species,
lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...
s consistently associated with lymphocystis included
hypertrophied Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.Updated by Linda J. ...
cells displaying irregular nuclei,
basophilic Basophilic is a technical term used by pathologists. It describes the appearance of cells, tissues and cellular structures as seen through the microscope after a histological section has been stained with a basic dye. The most common such dye is ...
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
ic
inclusion bodies Inclusion bodies are aggregates of specific types of protein found in neurons, a number of tissue cells including red blood cells, bacteria, viruses, and plants. Inclusion bodies of aggregations of multiple proteins are also found in muscle cells ...
that stained positively via Feulgen and Mann's reaction and Periodic acid-Shiff (PAS)-positive hyaline capsules. Hyaline capsules arise from the extracellular matrix that is produced by the infected cells, and are composed of sulphated and carboxylated glycoproteins (acid mucopolysaccharides). In contrast, the inclusion body shape, distribution of viral particles within the cytoplasm and overall appearance of lymphocystis nodules varied by species. The species examined in this study included the white-spotted puffer (''
Arothron hispidus The white-spotted puffer fish (''Arothron hispidus'') is a medium to large-sized puffer fish, it can reach 50 cm length. It is light grey in color, or greyish or yellowish, and clearly covered with more or less regular white points, that b ...
''), the Japanese sea bass (''
Lateolabrax japonicus The Japanese sea bass (''Lateolabrax japonicus'') is a species of catadromous marine ray-finned fish from the Asian sea bass family Lateolabracidae which is found in the Western Pacific. In Japan this species is known as . Description The Jap ...
''), olive flounder (''
Paralichthys olivaceus The olive flounder (''Paralichthys olivaceus''), bastard halibut or Japanese halibut, is a temperate marine species of large-tooth flounder native to the North-western Pacific Ocean. It is often referred to as the Japanese flatfish or Korean fla ...
'') and the "sting fish" or Schlegel's black rockfish ('' Sebastes schegeli'')


Serology

Several serologic assays have been developed to identify LCDV infections, including
flow cytometry Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the flo ...
,
immunoblot The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...
, and
immunofluorescence Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specif ...
. However, PCR-based molecular assays are more practical for most applications.


Electron microscopy

Transmission electron microscopy Transmission electron microscopy (TEM) is a microscopy technique in which a beam of electrons is transmitted through a specimen to form an image. The specimen is most often an ultrathin section less than 100 nm thick or a suspension on a g ...
(TEM) of infected cells reveals cytoplasmic virus particles typically measuring from 198-227 nm in diameter (in some cases as large as 380 nm) and electron-dense substances in the
perinuclear space The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membra ...
.


Molecular pathology

Published PCR primers and protocol are available to amplify a portion of the LCDV-1 MCP. When the PCR diagnostic assay is combined with slot blot, diagnostic sensitivity is increased, facilitating the diagnosis of asymptomatic LCDV-1 infections.


References


External links


ICTV Online (10th) Report: Iridoviridae
{{Taxonbar, from=Q6708248 Iridoviridae Fish viral diseases Virus genera