ERV FAQ: Why do virologists and geneticists think that ERVs come from retroviruses? Isn't that just supposition on their part?
Much material in this page has been lifted from Abbie Smith.Hope you don't mind Abbie, :D
Every detail of every full ERV is replete with complex and subtle details attesting to its origin in retroviruses. ERVs have the same structure as retroviral integrations. This is some -10 kilobases of genes specific to the retroviral replication cycle. All retroviruses and complete ERVs include genes we call gag, pol and env. The function of these genes will be gone into in detail in the following notes. In addition, several other features common to retroviral integrations and ERVs only make sense in terms of the requirements of the retroviral replication cycle.
"The gag gene encodes for ‘Gag’ the giant protein, which gets chopped into several smaller proteins, Matrix, Capsid, and Nucleocapsid (and sometimes a few more tiny ones, depending on the retrovirus)."
"Matrix is the structural protein just inside the envelope (the membrane the virus stole from its host cell). It has ‘outside’ functions (targeting the virus assembly to the right kind of cell membrane, keeping the outside protein env, in order) and ‘inside’ functions (targeting the reverse transcribed DNA to the new host cell nucleus). Jack of all trades protein, like lots of retroviral proteins. They run a tight ship."
"Capsid forms the viral ‘core’. Normally when you think of a ‘virus’, you think of this shape, an icosahedron. Retroviral ‘cores’ really look more like a cylinder-cone-thingie, like the bottom pic here. That particular pic is also worth a second look– More protein cuts to Capsid need to take place after a baby virus buds off from its host cell to make an immature virus mature. Blocking this maturation step is what the next family of anti-HIV-1 retrovirals do. *thumbs up*"
"Nucleocapsid is a structural protein that wraps up the retroviral genome to make sure its packaged properly into the Capsid."
Pol codes for all the enzymes a retrovirus needs:"
"Protease– Chomps big proteins into all the little functional proteins, like we saw with Gag getting chomped into Matrix/Capsid/Nucleocapsid. The name ‘protease’ can be a little confusing because all organisms have ‘proteases‘, but only the protease that the retrovirus carries with it is the ‘right‘ protease to cleave in all the ‘right’ spots to get all the ‘right’ proteins in the end. Instead of giving retroviral proteases a special name, they just named it ‘Protease’. heh. Protease inhibitors are a great target for anti-retrovirals."
"Reverse Transcriptase– Another target for anti-retrovirals. Though the process of reverse transcription can be found in you and I (coooool), retroviruses need to carry an enzyme with them to convert viral RNA into DNA on demand. This process not only requires converting an RNA genome into a DNA genome, but also:"
"RNase H– The RT enzyme has (at least) two active sites. One performs the process of reverse transcription. Another active site has RNase activity (chops up RNA, specifically, RNA Hybridized with DNA haha!). RNase H chews up the old RNA template after a single strand of DNA has been made, so the single strand of DNA can be made into double stranded DNA, and subsequently inserted into the host cells genome. This might make more sense if you see this animation. *might* The process of reverse transcription is rather absurd."
"Integrase– Host cells don't come packed with the necessary biochemical machinery to move DNA out of the cytoplasm into the nucleus, to be inserted into the host DNA. So once again, retroviruses need to bring an enzyme capable of performing those activities. Integrase should be a perfect target for antiretrovirals… But we havent figured any out yet…"
Env. See http://scienceblogs.com/erv/2008/07/17/intro-to-ervs-envy-my-env/
LTRs. See this page. RNA polymerase's normal function is to convert nuclear DNA into messenger RNA that makes for proteins. It does not normally make RNA that 'codes" for promoters. Our bodies have no need for them. But retroviruses need their promoters to be converted back to RNA for when the replication cycle begins again. Long terminal repeats (LTRs) cause the RNA polymerase to produce them by a complicated "hack". The point is, that LTRs basic and original function is a part of the replication process of retroviruses. They cannot be part of any supposed original "design" of our genomes. That would not make any sense.
See http://barryhisblog.blogspot.fr/p/ervs-promote-transcription-of-host-dna.html and http://scienceblogs.com/erv/2009/07/16/intro-to-ervs-ltr-gator
Retroviruses exhibit the distinctive viral codon bias.
The Phoenix virus was resurrected from the multiple instances of an ERV which is to be found in each human cell. Each instance is a 'failed' retrovirus, but when a 'majority vote' for each base was taken, the resulting DNA produced, "viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny." See also The "Phoenix Virus": an explanation of an experiment.
A retrovirus has been caught in the act of becoming endogenized: See The koala retrovirus KoRV and The Koala's Tale.
Retroviruses leave a telltale trace of integration in the form of a repeated host sequence either side of the integrated provirus. This is also evident in ERVs. From Virology Blog: Retroviral Integration and the XMRV Provirus, "The image below shows some of the characteristic features of retroviral integration. A the top is the unintegrated linear DNA of avian sarcoma/leukosis virus produced by reverse transcription. Upon completion of integration, two base pairs (AA•TT) are lost from both termini, and a 6-bp target site in host DNA (pink) is duplicated on either side of the proviral DNA. This target site varies in length from 4 to 6 bp among different retroviruses. The proviral DNA (middle) ends with the conserved 5′-T G…C A-3′ sequence. The provirus serves as a template for the production of the viral RNA genome (bottom)."
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