ME, retroviruses and prions

A family of gammaretroviruses (HGRVs) has been discovered in the blood of people with ME.  These viruses in mice (MuLVs) are notorious for causing neuro-immune disease and cancer.  Is it possible that in humans it is the relationship of these viruses to PrP, a cellular prion protein found in humans and other animals, which creates the multi-systemic disease Myalgic Encephalomyelitis (ME)?

Cellular prion proteins are essential for normal neurological and immune function, but in their misfolded form they can lead to a number of diseases, such as Creutzfeld-Jakob disease (CJD).

As can be seen from the following excerpt from Gabus et al. (2001), MuLVs in particular are also believed to interact with misfolded prions.  This interaction between the retroviruses and prions is called “nucleotide chaperoning”.

“Although PrP is a highly conserved protein in vertebrates, its role remains to be identified. Interestingly, PrP null mice develop normally and appear to be healthy (2). Nonetheless, a number of functions have been proposed for PrP such as super- oxide dismutase activity, involvement in copper metabolism (reviewed in Ref. 10), and, very recently, participation in signal transduction during neuronal differentiation (11). In addition, PrP was shown to interact with sulfated glycans (12), RNA aptamers (13), and large nucleic acids (14, 15), causing the formation of nucleoprotein complexes similar to HIV-1 nucleo- capsid-RNA complexes formed in vitro (16). A recent report shows that MuLV replication accelerates the scrapie infectious process (17), suggesting possible in vivo interactions between retroviruses and PrP.” 

http://www.jbc.org/content/276/22/19301.full.pdf

If a retrovirus infection caused cellular prion protein misfolding, via nucleotide chaperoning and vice versa, we have a mechanism that would result in a multisystemic disease.

WHERE DOES THE NUCLOTIDE CHAPERONING TAKE PLACE?

Prions and retroviruses both make use of exosomes and endosomes, which act like tiny cellular submarines, ferrying proteins between different islands in a cell and between cells.  Retroviruses specifically use exosomes and endosomes like submarines to disguise themselves and avoid the immune response, whilst prions travel between the surface of the cell membranes and the inside chambers of the cellular islands (organelles).

The shared use of these submarines allows for the retroviruses and prions to meet and interfere with each other, potentially changing the shape of each other’s proteins.  Once started each will increase the number of misfolded proteins of the other, over and over again.

SUPPORTING EVIDENCE

• Gammaretroviruses are known to increase the number of mishapen prions  and gammaretroviruses are known to cause spongiform encephalopathies.  Mad cow disease is an example.

• Change a prions shape and you get neuroimmune toxicity.

• Change shape of retrovirus proteins and you get neuroimmune toxicity.

• MuLVs cause neurotoxicity in mice as a result of a misfolded env protein (region of the virus), which is not incorporated into the virion.

• In 40% of HIV patients on HAART neurotoxicity still occurs despite the HAART treatment. 

 So could ME be a prion disease?