While Ive mentioned the connection between endogenous retroviruses and Multiple Sclerosis on teh blag before, I realized Ive never written a post on this topic. Fortunately I just read an interesting paper thats provided me with a good opportunity to do just that:
In addition to being ‘cancer’ viruses, it seems like another trick retroviruses are good at is screwing with our central nervous system. For example, HIV-1 infection leads to HIV associated dementia, and an effect of HTLV-1 infection is tropical spastic paraparesis (your myelin gets shredded).
Of course, other viruses can wreck havoc on your brain if they get in, this isnt specific to retroviruses (remember HSV-1?), but researchers have made a connection between retroviruses ability to demyelinate neurons, and the demyelination of neurons in multiple sclerosis patients, and endogenous retroviruses.
CAE had a neat post on this a while back, but basically, we can find HERV-W (a family of human ERVs) envelope proteins in MS patients lesions, but not in normal brains. Yay! An avenue to develop new treatments!
… But the HERV-W family used to be a gammaretrovirus.
How can we be certain that MS is associated with an endogenous retrovirus? How do we know MS isnt caused by a brand new infection by an exogenous retrovirus?
The HERV-W family is composed of about 650 elements. 280 of which contain some kind of gene, while the rest are just solo LTRs that have ‘popped out’ their coding sequence.
None of the remaining coding sequences can make a replication competent virus.
BUT! A handful of the coding sequences can make complete, or almost complete envelope proteins. One of these complete envs we know as ERVWE1, and under a different name, Syncytin-1– the protein that helps make placentas.
So there are only a few potential ‘complete-ish’ HERV-W envelope proteins that could be contributing to MS. If we find envelope mRNA that does NOT match up to theses few sequences perfectly… if we see a shitload of variation in these envelope sequences (a la HIV-1)… holy crap, there might be a ‘new’ retrovirus out there causing MS.
Happily (?) when Laufer et al sequenced the retroviral transcripts isolated from MS/nonMS patients, everything matched up to endogenous HERV-W genes, or combinations of them (half one HERV-W env, half another, etc). The ‘HERV-W’ protein we are seeing in the brains of MS patients is endogenous.
But Laufer and crew did find some odd things…
1– They used PBMC (blood immune cells), not astrocytes or glial cells… but they found HERV-W transcripts in both populations. OMFG JUNK RNA OH NOEZ!!! Yes, sometimes transcription is just noise. You have to look at protein levels, not just RNA levels, and this lab admittedly didnt.
2– Syncytin-1 is not the only HERV-W capable of coding a pretty-complete env. We assumed the protein present in MS patients lesions was Syncytin (leading to ‘WTF is placenta gene doing turned on in brains??), but its probably actually a different HERV-W env on the X chromosome, Xq22.3 (also found in chimpanzees. animal model! w00t!).
So dont worry, you arent going to get infected by with an ‘Multiple Sclerosis Virus’ from kissing someone or having sex without a condom. You were infected with the virus associated with MS tens of millions of years ago.