Enzootic nasal tumor virus

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Enzootic nasal tumor virus
Ewe infected with enzootic nasal adenocarcinome (sheep).jpg
Ewe infected with enzootic nasal tumor virus.
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Genus: Betaretrovirus
Virus:
Enzootic nasal tumor virus

The enzootic nasal tumor virus of the betaretrovirus genus is a carcinogenic retrovirus that causes enzootic nasal adenocarcinoma in sheep and goats. [1] Strain ENTV-1 is found in sheep and strain ENTV-2 is found in goats. [2] [3] The virus causes tumor growth in the upper nasal cavity and is closely related to JSRV which also causes respiratory tumors in ovine. [4] The disease, enzootic nasal adenocarcinoma is common in North America and is found in sheep and goats on every continent except New Zealand and Australia. [5] There are more than 27 betaretroviruses similar to ENVT and JSRV in the ovine genome. [6] [7] In the future, research on ENTV may become important in studying viruses that cause human lung cancer. [8]

Contents

Classification

ENTV belongs to the family Retroviridae , to the subfamily Orthoretrovirinae and the genus Betaretrovirus .[ citation needed ]

Associated disease

Enzootic nasal adenocarcinoma

The tumors that are induced by ENTV Env have characteristics of adenomas and adenocarcinoma due to well-differentiated epithelial appearance and a less well-differentiated appearance respectively. [9] Symptoms of nasal adenocarcinoma are similar in both goats and sheep. They include weight loss, nasal discharge with the nasal fluid being viscous and containing pus. Tumors form in the upper nasal cavity and have a gelatinous consistency with caudal areas being having hemorrhage causing a brownish-red color. [4] Symptoms of enzootic nasal adenocarcinoma do not appear until it is too late. An ovine that grows a tumor will eventually die of suffocation. [6]

Host interactions

Pathogenesis

Tumors form in nose and are contagious. ENTV targets the respiratory system in ovine, specifically the upper-airway epithelial cells. [6] Oncogenesis occurs in the nasal turbinate cells [8] A typical oncogenic virus will cause a mutation in a host cell, causing the transformation of host cells from a protooncogene into an oncogene. ENTV is unique among retroviruses because the envelope glycoprotein is an oncogene. It is able to induce tumors by itself. [10]   ENTV does not have a viremic stage where the virus enters the blood which is unusual. [11]

Immune response

There is not a humoral immune response to the ENTV capsid protein meaning there are no antibodies produced by the host in response to the virus capsid. [12]  However, recent studies have shown that there is sero-conversion in response to the envelope protein if a host is exposed to the virus after a long period of time. These antibodies have proven to be important in preventing further spread of the virus. The antibodies are more likely to respond to the ENTV envelope than the capsid because the envelope is located on the exterior of the virus whereas the capsid is not. [13] The lack of an extensive immune response may be due to the face that a large portion of the ovine genome is made up of sequences that are related to the retroviruses JSRV and ENTV.[ citation needed ]

Genome structure

ENTV has a conical structure and a similar genome structure as other retroviruses with the basic structure, 5’-U5-Gag-Pro-Pol-Env-U3-3’. ENTV has characteristics of both a B type retrovirus and a D type retrovirus. Its envelope is type B and its capsid protein is type D. This means that ENTV is classified as a chimeric type B/D retrovirus. [2] ENTV and JSRV's amino acids are similar by over 95%. This closely links the two viruses and leads to many studies comparing and contrasting the two. The 3’ end of env and the U3 LTR region contain amino acids with the least similarity making these areas important in scientific studies. ENTV 1 and ENTV 2 differ slightly in their genome. Their main differences occur in LTR, Orf-x, several regions in Gag and env TM. It is thought that this difference in the Env TM cytoplasmic tail is important in the spreading of the virus to host species. [4]

Gag

ENTV gag encodes a chain of amino acids linked by peptide bonds, or a polypeptide that contains 613 amino acids. Gag is also responsible for encoding structural proteins including the capsid protein, the matrix shell and the nucleic acid binding protein. [2]

Pro

Pro encodes a 326 amino acid polypeptide and generally works with gag to form a gag-pro polypeptide due to ribosomal frame shifting. It encodes the viral protease which breaks down the viral proteins into peptides and amino acids. [2]

Pol

Pol encodes a 870 amino acid peptide. It is usually translated to make a gag-pro-pol polypeptide due to ribosomal frame shifting. Inside the pol gene is an open reading frame, Orf-x which is abnormal for simple retroviruses. Pol is important because it encodes reverse transcriptase and integrase. [2]

Env

Env is generated by splicing and overlaps pol at the start. It encodes surface and transmembrane envelope proteins by being cleaved twice, a polypeptide precursor, and a hydrophobic region. Env plays a large role in the functionality of ENTV. [2] Env is important in ENVT tissue selectivity. [7]

LTR

LTR is 374 bases long and contains the primer binding site and the polypurine tract. It is made up of inverted repeat sequences GCAG and CTGC. tRNALys1,2 is the reverse transcriptase primer for ENVT. [2] The U3 region of LTR is important for replication and transcription regulatory signaling. [4] The U3 region is also important in tissue selectivity. [7]

Receptor and entry

The cellular receptor for ENTV is hyaluronidase 2 (Hyal2) in sheep. Hyal2 is a cell surface molecule that is anchored by glycosylphosphatidylinositol.  ENTV's binding is very restrictive compared to other retroviruses but it is also able to bind to human and bovine Hyal2 homologs. [8] ENTV entry is pH-dependent which is a unique feature among retroviruses. An extremely low pH of 4.5 is needed for the virus to perform fusion activation and cell entry this is much lower than JSRV which requires a ph of around 6. Fusion activation of ENTV requires a lower pH than cell entry. [14] An over expression of Hya2 is required for ENTV infection. ENTV may prefer to replicate in the nasal turbinate chondrocytes because of the high concentration of the receptor. [7] The low pH is beneficial to the virus by creating a tumor prone environment that activates HA degradation enzymes. [15] The TM subunit of the env gene plays an important role in the entry of ENTV into a cell. [2]  The SU subunit of the env gene also plays an important role in cell entry by influencing the low pH-dependent fusion activity. [14]

See also

Related Research Articles

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

A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds.

<span class="mw-page-title-main">Ovine pulmonary adenocarcinoma</span>

Ovine pulmonary adenocarcinoma (OPA), also known as ovine pulmonary adenomatosis, or jaagsiekte, is a chronic and contagious disease of the lungs of sheep and goats. OPA is caused by a retrovirus called jaagsiekte sheep retrovirus (JSRV).

Lentivirus is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Lentiviruses are distributed worldwide, and are known to be hosted in apes, cows, goats, horses, cats, and sheep as well as several other mammals.

Betaretrovirus is a genus of the Retroviridae family. It has type B or type D morphology. The type B is common for a few exogenous, vertically transmitted and endogenous viruses of mice; some primate and sheep viruses are the type D.

<i>Gammaretrovirus</i> Genus of viruses

Gammaretrovirus is a genus in the Retroviridae family. Example species are the murine leukemia virus and the feline leukemia virus. They cause various sarcomas, leukemias and immune deficiencies in mammals, reptiles and birds.

<span class="mw-page-title-main">Endogenous retrovirus</span> Inherited retrovirus encoded in an organisms genome

Endogenous retroviruses (ERVs) are endogenous viral elements in the genome that closely resemble and can be derived from retroviruses. They are abundant in the genomes of jawed vertebrates, and they comprise up to 5–8% of the human genome.

The genome and proteins of HIV (human immunodeficiency virus) have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.

<i>Jaagsiekte sheep retrovirus</i> Species of virus

Jaagsiekte sheep retrovirus (JSRV) is a betaretrovirus which is the causative agent of a contagious lung cancer in sheep, called ovine pulmonary adenocarcinoma.

Rous sarcoma virus (RSV) is a retrovirus and is the first oncovirus to have been described. It causes sarcoma in chickens.

Simian foamy virus (SFV) is a species of the genus Spumavirus that belongs to the family of Retroviridae. It has been identified in a wide variety of primates, including prosimians, New World and Old World monkeys, as well as apes, and each species has been shown to harbor a unique (species-specific) strain of SFV, including African green monkeys, baboons, macaques, and chimpanzees. As it is related to the more well-known retrovirus human immunodeficiency virus (HIV), its discovery in primates has led to some speculation that HIV may have been spread to the human species in Africa through contact with blood from apes, monkeys, and other primates, most likely through bushmeat-hunting practices.

Group-specific antigen, or gag, is the polyprotein that contains the core structural proteins of an Ortervirus. It was named as such because scientists used to believe it was antigenic. Now it is known that it makes up the inner shell, not the envelope exposed outside. It makes up all the structural units of viral conformation and provides supportive framework for mature virion.

Visna-maedi virus from the genus Lentivirus and subfamily Orthoretrovirinae, is a retrovirus that causes encephalitis and chronic pneumonitis in sheep. It is known as visna when found in the brain, and maedi when infecting the lungs. Lifelong, persistent infections in sheep occur in the lungs, lymph nodes, spleen, joints, central nervous system, and mammary glands; The condition is sometimes known as ovine progressive pneumonia (OPP), particularly in the United States, or Montana sheep disease. White blood cells of the monocyte/macrophage lineage are the main target of the virus.

<span class="mw-page-title-main">Syncytin-1</span> Protein-coding gene in the species Homo sapiens

Syncytin-1 also known as enverin is a protein found in humans and other primates that is encoded by the ERVW-1 gene. Syncytin-1 is a cell-cell fusion protein whose function is best characterized in placental development. The placenta in turn aids in embryo attachment to the uterus and establishment of a nutrient supply.

<span class="mw-page-title-main">Syncytin-2</span> Protein-coding gene in the species Homo sapiens

Syncytin-2 also known as endogenous retrovirus group FRD member 1 is a protein that in humans is encoded by the ERVFRD-1 gene. This protein plays a key role in the implantation of human embryos in the womb.

Avian sarcoma leukosis virus (ASLV) is an endogenous retrovirus that infects and can lead to cancer in chickens; experimentally it can infect other species of birds and mammals. ASLV replicates in chicken embryo fibroblasts, the cells that contribute to the formation of connective tissues. Different forms of the disease exist, including lymphoblastic, erythroblastic, and osteopetrotic.

Retroviral matrix proteins are components of envelope-associated capsids of retroviruses. These proteins line the inner surface of viral envelopes and are associated with viral membranes.

Mason-Pfizer monkey virus (M-PMV), formerly Simian retrovirus (SRV), is a species of retroviruses that usually infect and cause a fatal immune deficiency in Asian macaques. The ssRNA virus appears sporadically in mammary carcinoma of captive macaques at breeding facilities which expected as the natural host, but the prevalence of this virus in feral macaques remains unknown. M-PMV was transmitted naturally by virus-containing body fluids, via biting, scratching, grooming, and fighting. Cross contaminated instruments or equipment (fomite) can also spread this virus among animals.

Human Endogenous Retrovirus-W (HERV-W) is a family of Human Endogenous Retroviruses, or HERVs.

Bovine foamy virus (BFV) is a ss(+)RNA retrovirus that belongs to the genus spumaviridae. Spumaviruses differ from the other six members of family retroviridae, both structurally and in pathogenic nature. Spumaviruses derive their name from spuma the latin for "foam". The 'foam' aspect of 'foamy virus' comes from syncytium formation and the rapid vacuolization of infected cells, creating a 'foamy' appearance.

Enzootic nasal adenocarcinoma is a fatal, malignant neoplastic, infectious disease in sheep and goats. It is caused by the Enzootic nasal tumor virus, a retrovirus similar to Jaagsiekte sheep retrovirus, which causes a similar disease, also in sheep and goats called Ovine pulmonary adenocarcinoma (OPA). Symptoms include nasal discharge, dyspnea, facial deformity, and weight loss. Like OPA, the disease has a very long incubation period and is invariably fatal.

References

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