Endogenous retrovirus
Encyclopedia
Germ cell
A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by...
s in human
Human
Humans are the only living species in the Homo genus...
s, mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s and other vertebrates; as such their provirus
Provirus
A provirus is a virus genome that is integrated into the DNA of a host cell.This state can be a stage of virus replication, or a state that persists over longer periods of time as either inactive viral infections or an endogenous retrovirus. In inactive viral infections the virus will not replicate...
es are passed on
Inheritance
Inheritance is the practice of passing on property, titles, debts, rights and obligations upon the death of an individual. It has long played an important role in human societies...
to the next generation and now remain in the genome
Genome
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....
.
Hypothesis of origin
Endogenous retroviruses may be a variant of a retrovirusRetrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
which became permanently integrated with its host and is inherited from generation to generation as part of the genome of the host.
Retroviruses are single-stranded RNA 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 that reverse-transcribe their RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
into DNA
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...
for integration into the host's genome. Most retroviruses (such as HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
-1) infect somatic cells, but in very rare cases, it is thought that exogenous retroviruses have infected germline
Germline
In biology and genetics, the germline of a mature or developing individual is the line of germ cells that have genetic material that may be passed to a child.For example, gametes such as the sperm or the egg, are part of the germline...
cells (cells that make eggs and sperm) allowing integrated retroviral genetic sequences to be passed on to subsequent progeny, thereby becoming 'endogenous'. Endogenous retroviruses have persisted in the genome of their hosts for thousands of years. However, they are generally only infectious for a short time after integration as they acquire many inactivating mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s during host 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...
. They can also be partially excised from the genome by a process known as recombinational deletion. They are thought to play a key role in evolution. Some human ERVs have been implicated in ALS
ALS
ALS refers to amyotrophic lateral sclerosis, also known as Lou Gehrig's diseaseIt may also refer to:-Medicine:* Advanced life support, a level of medical training* Anterolateral system, part of the nervous system...
, certain autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
s, and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s.
Human endogenous retroviruses
Human endogenous retroviruses (HERVs) are suspected of involvement in some autoimmune diseaseAutoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
s, in particular with multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
. In this disease, there appears to be a specially associated member of the family of human endogenous retrovirus W
ERVWE1
HERV-W_7q21.2 provirus ancestral Env polyprotein also known as Env-W or enverin or syncytin is a protein that in humans is encoded by the ERVWE1 gene.- Function :...
known as "MS-associated retrovirus" (MSRV).
Thousands of endogenous retroviruses exist in human DNA. HERVs make up 98,000 elements and fragments—nearly 8%—of the human genome. According to a study published in 2005, no HERVs capable of replication had been identified; all appeared to be defective, containing major deletions or nonsense mutations. This is because most HERVs are merely traces of original viruses, having first integrated millions of years ago. However, one family of viruses has been active since the divergence of human
Human
Humans are the only living species in the Homo genus...
s and chimpanzee
Chimpanzee
Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...
s. This family, termed HERV-K (HML2), makes up less than 1% of HERV elements but is one of the most studied. There are indications it has even been active in the past few hundred thousand years, e.g., some human individuals carry more copies of the virus family than others . Traditionally, age estimates of HERVs are performed by comparing the 5' and 3' LTR
Long terminal repeat
Long terminal repeats are sequences of DNA that repeat hundreds or thousands of times. They are found in retroviral DNA and in retrotransposons, flanking functional genes...
of a HERV; however, this method is only relevant for full-length HERVs. A recent method called cross-sectional dating uses variations within a single LTR to estimate the ages of HERV insertions. This method is more precise in estimating HERV ages and can be used for any HERV insertions. Cross-sectional dating has been used to suggest that two members of HERV-K(HML2), HERV-K106, and HERV-K116 were active in the last 800,000 years and that HERV-K106 may have infected modern humans 150,000 years ago . However, the absence of known infectious members of the HERV-K(HML2) family, and the lack of elements with a full coding potential within the published human genome sequence, suggests to some that the family is less likely to be active at present.
In 2004 it was reported that antibodies to HERVs were found in greater frequency in the sera of people with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. Additionally, the cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
of people with recent onset schizophrenia contained levels of a retroviral marker, reverse transcriptase
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
, four times higher than control subjects. Researchers continue to look at a possible link between HERVs and schizophrenia, with the additional possibility of a triggering infection inducing schizophrenia.
In 2006, researchers led by Thierry Heidmann at the Institut Gustave Roussy
Institut Gustave Roussy
The Institut Gustave-Roussy is one of the world’s leading cancer-research institutes and the biggest health center dedicated to oncology in Europe. It is located in Villejuif, South Paris, France...
in Villejuif
Villejuif
Villejuif is a commune in the southern suburbs of Paris, France. It is located from the centre of Paris.-Name:The name Villejuif was recorded for the first time in a papal bull of 1119 as Villa Judea, the meaning of which is still debated...
, France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
, were able to recreate a HERV, which they dubbed Phoenix.
In 2007, a group led by Doug Nixon and Keith Garrison at the University of California, San Francisco
University of California, San Francisco
The University of California, San Francisco is one of the world's leading centers of health sciences research, patient care, and education. UCSF's medical, pharmacy, dentistry, nursing, and graduate schools are among the top health science professional schools in the world...
, and by Mario Ostrowski and Brad Jones at the University of Toronto
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
, published a study providing evidence for T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
immune responses against HERVs in HIV-infected individuals. The group hypothesized that HIV induces HERV expression in HIV infected cells, and that a vaccine targeting HERV antigens could therefore specifically eliminate HIV infected cells. The potential advantage of this novel approach is that, by using HERV antigens as surrogate markers of HIV infected cells, it could circumvent the difficulty inherent in directly targeting notoriously diverse and fast-mutating HIV antigens.
See also
- Viral fossilViral fossilViral fossil is an informal term for pieces of genetic code of a virus in the genome of a modern-day host organism. These viruses and their insertions are called fossil viruses or paleoviruses. They may be traced to millions of years back, hence the terminology, although strictly speaking, it is...
- BacteriophageBacteriophageA bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
- RetrotransposonRetrotransposonRetrotransposons are genetic elements that can amplify themselves in a genome and are ubiquitous components of the DNA of many eukaryotic organisms. They are a subclass of transposon. They are particularly abundant in plants, where they are often a principal component of nuclear DNA...
- GermlineGermlineIn biology and genetics, the germline of a mature or developing individual is the line of germ cells that have genetic material that may be passed to a child.For example, gametes such as the sperm or the egg, are part of the germline...
- Horizontal gene transferHorizontal gene transferHorizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...