Human endogenous retrovirus K | |
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Virus classification | |
(unranked): | Virus |
Realm: | Riboviria |
Kingdom: | Pararnavirae |
Phylum: | Artverviricota |
Class: | Revtraviricetes |
Order: | Ortervirales |
Family: | Retroviridae |
Genus: | Betaretrovirus (?) |
(unranked): | Human endogenous retrovirus K |
Human endogenous retrovirus K (HERV-K) or Human teratocarcinoma-derived virus (HDTV) is a family of human endogenous retroviruses associated with malignant tumors of the testes. [1] [2] [3] [4] Phylogenetically, the HERV-K group belongs to the ERV2 or Class II or Betaretrovirus-like supergroup. [5] Over the past several years, it has been found that this group of ERVs play an important role in embryogenesis, but their expression is silenced in most cell types in healthy adults. [6] The HERV-K family, and particularly its subgroup HML-2, is the youngest and most transcriptionally active group and hence, it is the best studied among other ERVs. Reactivation of it or anomalous expression of HML-2 in adult tissues has been associated with various types of cancer [7] [8] [9] and with neurodegenerative diseases such as amytrophic lateral sclerosis (ALS). [10] [5] Endogenous retrovirus K (HERV-K) is related to mammary tumor virus in mice. It exists in the human and cercopithecoid genomes. Human genome contains hundreds of copies of HERV-K and many of them possess complete open reading frames (ORFs) that are transcribed and translated, especially in early embryogenesis and in malignancies. [5] [11] One notable [12] [13] [14] [15] location of HERV-K is the C4 gene of RCCX module. [16] [17] HERV-K is also found in apes and Old World monkeys. It is uncertain how long ago in primate evolution the full-length HERV-K proviruses which are in the human genome today were created. [18]
The human endogenous retrovirus K (HERV-K) was inherited million years ago by the genome of the human ancestors. [18] In 1999 Barbulescu, et al. showed that, of ten HERV-K proviruses cloned, eight were unique to humans, while one was shared with chimpanzees and bonobos, and one with chimpanzees, bonobos and gorillas. [19] Originally, HERV-K was observed by low-stringency hybridization with probes for the mammary tumor virus of the mouse and A particle intracutaneous mouse. [18]
In 2015 Grow et al. demonstrated that HERV-K is transcribed during embryogenesis from the eight cell stage up to the stem cell derivation. [20] Furthermore, overexpression of the HERV-K accessory protein Rec (regulator of expression encoded by corf; Pfam PF15695) increases IFITM1 levels on the cell surface and inhibits viral infection. [20] [21] HERV-K is called, phylogenetically, a supergroup of viruses. It is the only group that reported to contain human-specific members of endogenous retroviruses (ERVs). [22]
HERV-K is receptive to microenvironmental modifications and melanoma cells are closely correlated with epigenetic and microenvironmental anomalies. Also the association of HERV-K activation with carcinogenesis is especially interesting. [23]
A provirus is a virus genome that is integrated into the DNA of a host cell. In the case of bacterial viruses (bacteriophages), proviruses are often referred to as prophages. However, proviruses are distinctly different from prophages and these terms should not be used interchangeably. Unlike prophages, proviruses do not excise themselves from the host genome when the host cell is stressed.
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.
Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus like the HTL viruses, HI viruses, and BLV. It belongs to the genus Betaretrovirus. MMTV was formerly known as Bittner virus, and previously the "milk factor", referring to the extra-chromosomal vertical transmission of murine breast cancer by adoptive nursing, demonstrated in 1936, by John Joseph Bittner while working at the Jackson Laboratory in Bar Harbor, Maine. Bittner established the theory that a cancerous agent, or "milk factor", could be transmitted by cancerous mothers to young mice from a virus in their mother's milk. The majority of mammary tumors in mice are caused by mouse mammary tumor virus.
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.
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.
Jaagsiekte sheep retrovirus (JSRV) is a betaretrovirus which is the causative agent of a contagious lung cancer in sheep, called ovine pulmonary adenocarcinoma.
The murine leukemia viruses are retroviruses named for their ability to cause cancer in murine (mouse) hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses. Replicating MLVs have a positive sense, single-stranded RNA (ssRNA) genome that replicates through a DNA intermediate via the process of reverse transcription.
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.
HERV-R_7q21.2 provirus ancestral envelope (Env) polyprotein is a protein that in humans is encoded by the ERV3 gene.
HERV-K_19q12 provirus ancestral Pol protein is a protein that in humans is encoded by the ERVK6 gene.
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.
Beta-1,3-galactosyltransferase 5 is an enzyme that in humans is encoded by the B3GALT5 gene.
Koala retrovirus (KoRV) is a retrovirus that is present in many populations of koalas. It has been implicated as the agent of koala immune deficiency syndrome (KIDS), an AIDS-like immunodeficiency that leaves infected koalas more susceptible to infectious disease and cancers. The virus is thought to be a recently introduced exogenous virus that is also integrating into the koala genome. Thus the virus can transmit both horizontally and vertically. The horizontal modes of transmission are not well defined but are thought to require close contact.
Paleovirology is the study of viruses that existed in the past but are now extinct. In general, viruses cannot leave behind physical fossils, therefore indirect evidence is used to reconstruct the past. For example, viruses can cause evolution of their hosts, and the signatures of that evolution can be found and interpreted in the present day. Also, some viral genetic fragments which were integrated into germline cells of an ancient organism have been passed down to our time as viral fossils, or endogenous viral elements (EVEs). EVEs that originate from the integration of retroviruses are known as endogenous retroviruses, or ERVs, and most viral fossils are ERVs. They may preserve genetic code from millions of years ago, hence the "fossil" terminology, although no one has detected a virus in mineral fossils. The most surprising viral fossils originate from non-retroviral DNA and RNA viruses.
An endogenous viral element (EVE) is a DNA sequence derived from a virus, and present within the germline of a non-viral organism. EVEs may be entire viral genomes (proviruses), or fragments of viral genomes. They arise when a viral DNA sequence becomes integrated into the genome of a germ cell that goes on to produce a viable organism. The newly established EVE can be inherited from one generation to the next as an allele in the host species, and may even reach fixation.
Human Endogenous Retrovirus-W (HERV-W) is a family of Human Endogenous Retroviruses, or HERVs.
MHC class III is a group of proteins belonging the class of major histocompatibility complex (MHC). Unlike other MHC types such as MHC class I and MHC class II, of which their structure and functions in immune response are well defined, MHC class III are poorly defined structurally and functionally. They are not involved in antigen binding. Only few of them are actually involved in immunity while many are signalling molecules in other cell communications. They are mainly known from their genes because their gene cluster is present between those of class I and class II. The gene cluster was discovered when genes were found in between class I and class II genes on the short (p) arm of human chromosome 6. It was later found that it contains many genes for different signalling molecules such as tumour necrosis factors (TNFs) and heat shock proteins. More than 60 MHC class III genes are described, which is about 28% of the total MHC genes (224). The region previously considered within MHC class III gene cluster that contains genes for TNFs is now known as MHC class IV or inflammatory region.
Gibbon-ape leukemia virus (GaLV) is an oncogenic, type C retrovirus that has been isolated from primate neoplasms, including the white-handed gibbon and woolly monkey. The virus was identified as the etiological agent of hematopoietic neoplasms, leukemias, and immune deficiencies within gibbons in 1971, during the epidemic of the late 1960s and early 1970s. Epidemiological research into the origins of GaLV has developed two hypotheses for the virus' emergence. These include cross-species transmission of the retrovirus present within a species of East Asian rodent or bat, and the inoculation or blood transfusion of a MbRV-related virus into captured gibbons populations housed at medical research institutions. The virus was subsequently identified in captive gibbon populations in Thailand, the US and Bermuda.
ERV-Fc was an endogenous retrovirus (ERV), or a genus or family of them, related to the modern murine leukemia virus. It was active and infectious among many species of mammals in several orders, jumping species more than 20 times between about 33 million and about 15 million years ago, in the Oligocene and early Miocene, in all large areas of the world except for Australia and Antarctica. After about 15 million years ago, it became extinct as an active infectious virus, perhaps due to its hosts developing inherited resistance to it, but inactive damaged copies and partial copies and fragments of its DNA survive as inclusions in the hereditary nuclear DNA of many species of mammals, some in different orders, including humans and other great apes. That has let interspecies jump routes of the spreading virus be tracked, and timed by the molecular clock in their extant descendants, but with gaps where trails were lost by passing through infected animals who left no extant descendants or by loss of the integrated sequence in some lineages.
RCCX is a complex, multiallelic, and tandem copy number variation (CNV) human DNA locus on chromosome 6p21.3, located in the major histocompatibility complex (MHC) class III region. CNVs are segments of DNA that vary in copy number compared to a reference genome and play a significant role in human phenotypic variation and disease development. The RCCX module consists of a series of genes close to each other: serine/threonine kinase 19 (STK19), complement 4 (C4), steroid 21-hydroxylase (CYP21), and tenascin-X (TNX).