Epizootic hemorrhagic disease virus

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Epizootic hemorrhagic disease virus
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Duplornaviricota
Class: Resentoviricetes
Order: Reovirales
Family: Sedoreoviridae
Genus: Orbivirus
Species:
Epizootic hemorrhagic disease virus

Epizootic hemorrhagic disease virus, often abbreviated to EHDV, is a species of the genus Orbivirus , a member of the family Reoviridae . It is the causative agent of epizootic hemorrhagic disease, an acute, infectious, and often fatal disease of wild ruminants. In North America, the most severely affected ruminant is the white-tailed deer (Odocoileus virginianus), although it may also infect mule deer, black-tailed deer, elk, bighorn sheep, and pronghorn antelope. [1] It is often mistakenly referred to as “bluetongue virus” (BTV), another Orbivirus that like EHDV causes the host to develop a characteristic blue tongue due to systemic hemorrhaging and lack of oxygen in the blood. [2] Despite showing clinical similarities, these two viruses are genetically distinct.

Contents

Worldwide, eight serotypes of EHDV have been identified. [3] Historically, only serotypes EHDV-1 and EHDV-2 have been found in North America, but recent research has discovered at least one more in the Midwest and Southern United States. [4] EHDV can only be spread by an insect vector. In North America, the common vector is the biting midge ( Culicoides variipennis ). The first identified outbreak of EHDV in the United States in 1955 caused several hundred white-tailed deer to die in New Jersey and Michigan. [2] Cases of EHDV-like die-offs have been reported prior to 1955 (as far back as 1890), but EHDV was not identified in these cases, as its existence was not yet known.

Viral classification

Epizootic hemorrhagic disease virus belongs to the family Reoviridae , a family of double-stranded RNA viruses that includes familiar genera Rotavirus (the most common cause of viral gastroenteritis in children), Coltivirus (causative agent of Colorado tick fever), and Orbivirus . Besides EHDV and BTV, other orbiviruses include equine encephalosis virus and African horse sickness virus . [5]

Genome and structure

Epizootic hemorrhagic disease virus's genome is about 18-31 kDa in length and consists of 10 segments, where each segment encodes a single protein. [6] These proteins could be one of the seven structural proteins (VP1-VP7) or one of the four non-structural proteins (NS1, NS2, NS3a, or NS3b). [7] The nonstructural proteins are encoded by gene segments 6, 8, and 10, and have been found to be highly conserved. The segmented genome of EHDV facilitates reassortment within species, and may be why EHDV breakouts occur every year. [8]

The virion outer layer is composed primarily of VP2 and VP5 trimers that are also involved in the virus's ability to attach to and penetrate a host cell. The outer core layer is formed by VP7, which provides a surface for VP2 and VP5 attachment, while the inner subcore layer is formed by VP3. The VP3 inner subcore layer self-assembles to control the size and organization of the capsid structure. The VP3 layer surrounds VP1, VP4, and VP6, in addition to the 10 linear double-stranded RNA segments. [9]

Eight serotypes of EHDV are proposed. Serotypes EHDV-1 (New Jersey strain) and EHDV-2 (Alberta strain) are the dominant forms of EHDV in the U.S., except for in 2012, when an outbreak of EHDV-6 accounted for 63% of the collected isolates from moribund or dead white-tailed deer in the environment. EHDV-6 is thought to be a hybrid form where each of the collected type-6 viruses were all reassortants containing VP2 and VP5 derived from an exotic EHDV-6, while the remaining structural and nonstructural proteins were obtained from the indigenous EHDV-2. EHDV-6 was originally described as originating from Australia, but it has been recognized as an emerging pathogen among cattle in several countries, and is now being considered as an endemic strain in certain parts of the U.S. [4]

Interaction with the host and associated diseases

Epizootic hemorrhagic disease virus must be transmitted via bites from Culicoides gnats ( C. verripennis ) and cannot be transmitted directly from deer to deer. EHDV manifests itself as epizootic hemorrhagic disease (EHD), which has similar symptoms to adenovirus hemorrhagic disease (AHD), “bluetongue” disease, and malignant catarrhal fever. Instead of being spread by a vector like EHDV, AHD is spread from animal to animal by direct contact and bodily fluids. [10] EHDV is also antigenically different from “bluetongue” disease but the clinical signs of each disease are very similar. EHDV causes deer to lose their fear of humans and causes weakness, excessive salivation, bloody diarrhea, fever, rapid pulse and rapid respiration rate. [10] Hemorrhage and lack of oxygen in the blood results in a blue appearance of the oral mucosa. [2] Bodies of infected deer are frequently found in bodies of water, where they laid down in an attempt to lower their body temperature before becoming unconscious and dying. These symptoms develop about 7 days after the animal was exposed to the virus and 8–36 hours after the onset of initial observable signs; deer progress into a shock-like state, collapse and die. [2]

Examinations of infected deer suggest the virus interferes with normal blood circulation and normal blood clotting mechanisms. The characteristic hemorrhaging of all EHDV victims is caused by an interference with blood clotting mechanisms along with the degeneration of blood vessel walls in many organs and tissues throughout the body. [2] Any alteration in the proteins such as fibrin that render them incapable of causing platelets to gather in a clot along a broken area of blood vessel wall will result in excessive bleeding outside of that vessel. All of this blood leaving blood vessels creates the hemorrhaging associated with this disease. Increased pericardial fluid and generalized edema consistently found in all cases of EHDV strongly suggest its interference with the normal circulation of blood. [2]

Since EHDV is transmitted by gnats, livestock can be exposed to the virus, as well. So far, livestock that have been exposed to this disease rarely show signs of infection. In cases where livestock have shown clinical symptoms, they are usually limited to symptoms such as fever, loss of appetite, lameness, and ulcers and crusty sores on the nose, mouth, and teats. [10]

Ibaraki virus, which is a strain of EHDV serotype 2, causes Ibaraki disease in cattle in Japan. [11]

Tropism

Studies investigating the transmission of the disease have found that it can be transmitted to susceptible deer by inoculating them with infected material from diseased deer by subcutaneous, intramuscular, intravenous, or oral routes in experimental settings. The specific tissues and organs that show hemorrhaging from EHDV vary animal to animal. The most common ones include the heart, liver, spleen, kidney, lung, and intestinal tract. Virus samples can be isolated from many kinds of tissues from infected animals, including blood, liver, spleen, kidney, lung, heart, and other muscles. [2]

Entry

Infecting viral particles are able to enter the cell via an endosmal route. The believed mechanism for this has to do with an acidification of the endosome, similar to what is done in the influenza virus. Early acidification of the endosome is thought to release components from the virus core. These components are then released into the host cell cytoplasm. [12] VP5 often catalyzes cell fusion, which facilitates the penetration of the endosomal membrane and consequently the release of outer capsid components. [13] ALthough EHDV does not contain large concentrations of VP5, it is still able to infect cell systems. [14] EHDV is able to be infectious due to the presence of VP7 as suggested by the binding of anti-bodies to the outer core protein VP7. The binding of EHDV to the cell surface via interaction of VP7 with glycosaminoglycans in addition to other receptors is the most probable entry mechanism. [15]

Replication and transmission

Because EHDV is a double-stranded RNA virus, it needs to overcome a specific set of problems, the main one being the fact that double-stranded RNA is unable to be used as template strand during mRNA translation using host cell machinery. Therefore, EHDV must bring its own transcription enzymes into the cell, to survive and synthesize viral RNA and proteins. However, antiviral defense mechanisms are able to easily recognize and eliminate naked double-stranded RNA in the cell. The presence of the double-stranded RNA would trigger antiviral mechanisms such as apoptosis and interferon production. [16] In order to bypass these host defenses, double-stranded RNA viruses such as EHDV “hide” their genome and other translation machinery within closed protein capsids. These capsids are then delivered into the host cell cytoplasm, where they initiate transcription. [17] The removal of viral proteins VP5 and VP2 during cell entry facilitates the transcription functions of the core, which allows EHDV to synthesize and cap full-length mRNA copies of up to 10 genome segments while they are still safely packaged with in the core.

Release

EHDV genome is assembled within the EHDV subcore, and core particles are assembled within protein capsids inside the cytoplasm of infected cells. The release of EHDV occurs through two main mechanisms: the common viral pathway of budding and by direct cell membrane penetration. The latter damages the cell, often leading to cell lysis. Budding is mediated by NS3. [12]

Related Research Articles

<span class="mw-page-title-main">Bluetongue disease</span> Viral disease in animals

Bluetongue disease is a noncontagious, insect-borne, viral disease of ruminants, mainly sheep and less frequently cattle, yaks, goats, buffalo, deer, dromedaries, and antelope. It is caused by Bluetongue virus (BTV). The virus is transmitted by the midges Culicoides imicola, Culicoides variipennis, and other culicoids.

Coxsackie B4 virus are enteroviruses that belong to the Picornaviridae family. These viruses can be found worldwide. They are positive-sense, single-stranded, non-enveloped RNA viruses with icosahedral geometry. Coxsackieviruses have two groups, A and B, each associated with different diseases. Coxsackievirus group A is known for causing hand-foot-and-mouth diseases while Group B, which contains six serotypes, can cause a varying range of symptoms like gastrointestinal distress myocarditis. Coxsackievirus B4 has a cell tropism for natural killer cells and pancreatic islet cells. Infection can lead to beta cell apoptosis which increases the risk of insulitis.

<span class="mw-page-title-main">Poliovirus</span> Enterovirus

Poliovirus, the causative agent of polio, is a serotype of the species Enterovirus C, in the family of Picornaviridae. There are three poliovirus serotypes: types 1, 2, and 3.

<span class="mw-page-title-main">Picornavirus</span> Family of viruses

Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm icosahedral capsid. The viruses in this family can cause a range of diseases including the common cold, poliomyelitis, meningitis, hepatitis, and paralysis.

<i>Birnaviridae</i> Family of viruses

Birnaviridae is a family of double-stranded RNA viruses. Salmonid fish, birds and insects serve as natural hosts. There are currently 11 species in this family, divided among seven genera. Diseases associated with this family include infectious pancreatic necrosis in salmonid fish, which causes significant losses to the aquaculture industry, with chronic infection in adult salmonid fish and acute viral disease in young salmonid fish.

<span class="mw-page-title-main">Adeno-associated virus</span> Species of virus

Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus Dependoparvovirus, which in turn belongs to the family Parvoviridae. They are small replication-defective, nonenveloped viruses and have linear single-stranded DNA (ssDNA) genome of approximately 4.8 kilobases (kb).

<i>Orbivirus</i> Genus of viruses

Orbivirus is a genus of double-stranded RNA viruses in the family Reoviridae and subfamily Sedoreovirinae. Unlike other reoviruses, orbiviruses are arboviruses. They can infect and replicate within a wide range of arthropod and vertebrate hosts. Orbiviruses are named after their characteristic doughnut-shaped capsomers.

<i>Aphthovirus</i> Genus of viruses

Aphthovirus is a viral genus of the family Picornaviridae. Aphthoviruses infect split-hooved animals, and include the causative agent of foot-and-mouth disease, Foot-and-mouth disease virus (FMDV). There are seven FMDV serotypes: A, O, C, SAT 1, SAT 2, SAT 3 and Asia 1, and four non-FMDV serotypes belonging to three additional species Bovine rhinitis A virus (BRAV), Bovine rhinitis B virus (BRBV) and Equine rhinitis A virus (ERAV).

Drosophila X virus (DXV) belongs to the Birnaviridae family of viruses. Birnaviridae currently consists of three genera. The first genus is Entomobirnavirus, which contains DXV. The next genus is Aquabirnavirus, containing infectious pancreatic necrosis virus (IPNV). The last genus is Avibirnavirus, which contains infectious bursal disease virus (IBDV). All of these genera contain homology in three specific areas of their transcripts. The homology comes from the amino and carboxyl regions of preVP2, a small 21-residue-long domain near the carboxyl terminal of VP3, and similar small ORFs sequences.

Gyrovirus is a genus of viruses, in the family Anelloviridae. Until 2011, chicken anemia virus was the only Gyrovirus identified, but since then gyroviruses have also been identified in humans. Diseases associated with this genus include: chicken infectious anemia, which is associated with depletion of cortical thymocytes and erythroblastoid cells.

<span class="mw-page-title-main">Double-stranded RNA viruses</span> Type of virus according to Baltimore classification

Double-stranded RNA viruses are a polyphyletic group of viruses that have double-stranded genomes made of ribonucleic acid. The double-stranded genome is used as a template by the viral RNA-dependent RNA polymerase (RdRp) to transcribe a positive-strand RNA functioning as messenger RNA (mRNA) for the host cell's ribosomes, which translate it into viral proteins. The positive-strand RNA can also be replicated by the RdRp to create a new double-stranded viral genome.

<i>Enterovirus E</i> Species of virus

Enterovirus E is a picornavirus of the genus Enterovirus. The virus may also be referred to as enteric cytopathic bovine orphan virus (ECBO). It is endemic in cattle populations worldwide, and although normally fairly nonpathogenic, it can cause reproductive, respiratory, or enteric disease – particularly when the animal is concurrently infected with another pathogen.

<span class="mw-page-title-main">Murine polyomavirus</span> Species of virus

Murine polyomavirus is an unenveloped double-stranded DNA virus of the polyomavirus family. The first member of the family discovered, it was originally identified by accident in the 1950s. A component of mouse leukemia extract capable of causing tumors, particularly in the parotid gland, in newborn mice was reported by Ludwik Gross in 1953 and identified as a virus by Sarah Stewart and Bernice Eddy at the National Cancer Institute, after whom it was once called "SE polyoma". Stewart and Eddy would go on to study related polyomaviruses such as SV40 that infect primates, including humans. These discoveries were widely reported at the time and formed the early stages of understanding of oncoviruses.

Liao ning virus (LNV) is a virus belonging to the genus Seadornavirus within the family Reoviridae, a family of segmented, non-enveloped, double-stranded RNA viruses. LNV was first discovered in Aedes dorsalis populations in the Liaoning province of the People's Republic of China in 2006 from mosquito samples obtained in 1997. Its geographic distribution was previously thought to be limited to China, but it has since been found in mosquito populations in Australia. In addition to Aedes dorsalis, LNV has been isolated from Culex species.

<i>Infectious pancreatic necrosis virus</i> RNA virus infecting salmonid fish

Infectious pancreatic necrosis virus (IPNV) is a double-stranded RNA virus from the family Birnaviridae, in the genus Aquabirnavirus. Causing the highly infectious disease Infectious pancreatic necrosis, the virus primarily affects young salmonids resulting in high mortality, occasionally surpassing 90 percent in the early stages. IPNV or IPNV-like viruses have been isolated worldwide from at least 32 families of saltwater and freshwater salmonids and non-salmonids fish including salmon, flatfish, pike, eels and others. Other aquatic organisms infected include 11 molluscs and 4 species of crustaceans. Due to its wide host range and high mortality, the virus is of great concern to global aquaculture. In addition to persistence in hosts, IPNV is also perpetual in the environment, surviving across a range of conditions and capable of infecting fish with as little as 101TCID50/ml of the virus. Found in Europe, North America, South America, Africa, Asia, and Australia, the virus has led to significant losses in the mariculture of Atlantic salmon, brook trout, and rainbow trout.

<span class="mw-page-title-main">Major capsid protein VP1</span>

Major capsid protein VP1 is a viral protein that is the main component of the polyomavirus capsid. VP1 monomers are generally around 350 amino acids long and are capable of self-assembly into an icosahedral structure consisting of 360 VP1 molecules organized into 72 pentamers. VP1 molecules possess a surface binding site that interacts with sialic acids attached to glycans, including some gangliosides, on the surfaces of cells to initiate the process of viral infection. The VP1 protein, along with capsid components VP2 and VP3, is expressed from the "late region" of the circular viral genome.

<i>Sedoreovirinae</i> Subfamily of viruses

Sedoreovirinae was a subfamily of the Reoviridae family of viruses. Viruses in this subfamily are distinguished by the absence of a turreted protein on the inner capsid to produce a smooth surface.

<i>Avibirnavirus</i> Genus of viruses

Avibirnavirus is a genus of viruses in family Birnaviridae. There is a single species in this genus: Infectious bursal disease virus, which infects chickens and other fowl. It causes severe inflammation of the bursa of Fabricius, and causes considerable morbidity and mortality.

Minor capsid protein VP2 and minor capsid protein VP3 are viral proteins that are components of the polyomavirus capsid. Polyomavirus capsids are composed of three proteins; the major component is major capsid protein VP1, which self-assembles into pentamers that in turn self-assemble into enclosed icosahedral structures. The minor components are VP2 and VP3, which bind in the interior of the capsid.

Triatoma virus (TrV) is a virus belonging to the insect virus family Dicistroviridae. Within this family, there are currently 3 genera and 15 species of virus. Triatoma virus belongs to the genus Cripavirus. It is non-enveloped and its genetic material is positive-sense, single-stranded RNA. The natural hosts of triatoma virus are invertebrates. TrV is a known pathogen to Triatoma infestans, the major vector of Chagas disease in Argentina which makes triatoma virus a major candidate for biological vector control as opposed to chemical insecticides. Triatoma virus was first discovered in 1984 when a survey of pathogens of triatomes was conducted in the hopes of finding potential biological control methods for T. infestans.

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