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Human Endogenous Retroviruses (HERVs)












Fig. 1. Electron microscopy of the viral-like particles generated by the Phoenix provirus transfected into human 293T cells. The prominent spikes of the Env protein are visible under hight magnification. (Dewannieux, M. et al., Genome Res. (2006) 16: gr.5565706)


The human genome contains about 8% of sequences of retroviral origin, remnants of different exogenous retrovirus infections of the germ line genome that occurred millions of years ago. Endogenous retroviruses may be a variant of a retrovirus that 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 viruses that reverse-transcribe their RNA into DNA for integration into the host's genome. Most retroviruses (such as HIV-1) infect somatic cells, but in very rare cases, it is thought that exogenous retroviruses have infected germline cells (cells that make eggs and sperm) allowing integrated retroviral genetic sequences to be passed on to subsequent offspring, 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 mutations during host DNA replication. 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.

Human endogenous retroviruses (HERVs) are suspected of involvement in some autoimmune diseases, and cancers and in particular with multiple sclerosis. In this disease, there appears to be a specially associated member of the family of human endogenous retrovirus-W known as MS-associated retrovirus (MSRV).

During pregnancy in mammals, ERVs are activated and produced in high quantities during the implantation of the embryo. They are hypothesized to possess immunosuppressive properties, suggesting a role in gestational immune tolerance, thereby protecting the embryo from its mother's immune system. Also, viral fusion proteins apparently cause the formation of the placental syncytium in order to limit the exchange of migratory cells between the developing embryo and the body of the mother. An immunoevasive action was the initial normal behavior of the viral protein, in order to assist the virus to spread to other cells by simply merging them with the infected one (HIV does this too). It is believed that the ancestors of mammals evolved after an infection by this virus, thus enabling the fetus to better resist the immune system of the mother.

HERV-K

There is one family of viruses that have been active since the divergence of humans and chimpanzees. This family, termed HERV-K (HML2), makes up less than 1% of HERV elements but is one of the most studied. The HERV-K family of endogenous retroelements is particularly interesting because there is some evidence that members of this family are still biologically active. There are implications for the presences of HERVs in several different disease states.

1. Most HERV-K members are transcriptionally active and, unlike many of the other sequenced HERV elements, the prototype HERV-K10 provirus contains very few mutations that interrupt the viral open reading frames.

2. There is evidence that HERV-K elements encode the retrovirus-like particles produced by the teratocarcinoma cell line GH and HERV-K10-like sequences were also found in particles produced by the mammary carcinoma cell line T47D.

3. Type 1 and type 2 HERV-K envelope (env) transcripts are expressed in most human breast cancers, but not in normal breast tissues.

4. It has been reported that antibodies to HERVs were found at greater frequency in the sera of people with schizophrenia. Additionally, the cerebrospinal fluid of people with recent onset schizophrenia contained levels of a retroviral marker, reverse transcriptase, four times higher than control subjects. Researchers continue to look at a possible link between HERVs and schizophrenia.


US Biological Human Endogenous Retrovirus (HERV) antibodies:

Cat #
Name
E2286 Endogenous Retrovirus (HERV, Enverin, ERVW, ERVWE1, HERVW, Syncytin, Syncytin 1) Pab Rb x        
E2286-05A HERV, ID (HERV-W_7q21.2 Provirus Ancestral Env Polyprotein, Envelope Polyprotein gPr73, HERV-7q Envelope Protein, HERV-W Envelope Protein, Syncytin, Syncytin-1, Enverin, Env-W, ERVWE1) Pab Rb xHu        
E2286-10 Endogenous Retrovirus Type K, Human, Capsid Protein (HERV K, Enverin, ERVW, ERVWE1, HERVW, Syncytin, Syncytin 1) Mab Mo x
E2286-13 Endogenous Retrovirus Type K, Human, Envelope Protein (HERV K, Enverin, ERVW, ERVWE1, HERVW, Syncytin, Syncytin 1) Mab Mo x        
E2286-14 Endogenous Retrovirus Type K, Human, Envelope Protein (HERV K, Enverin, ERVW, ERVWE1, HERVW, Syncytin, Syncytin 1) Mab Mo x        
E2286-19 Endogenous Retrovirus Type K, Human, gag protein (HERV K, Enverin, ERVW, ERVWE1, HERVW, Syncytin, Syncytin 1)) Mab Mo x