Hi everybody,
The fact of knowing I am XMRV+ gave me a very good incentive to study in depth and trying to understand all the studies published to date about XMRV and related retroviruses and CFS. My objective is to create a database in Spanish (I couldn’t do it in English and also I don’t think it’s necessary…) explaining in layman’s language every single study and its meaning in practical terms, and for that purpose I do need to understand everything in detail.
Ok, here is the problem, I do need a lot of basic background on a lot of difference disciplines to understand first the basic things, in order to be able to comprehend the necessary concepts. Ok, thanks to Wikipedia (what could we do without it? :victory
and Internet in general I am managing, but I do have a limit, and need help!Sooooo, for those who are ahead of me in understanding all this staff, I beg for some help! So here are my doubts of today
:I am trying to figure out the differences between XMRV and the rest of MLVs.
Ok, it seems clear from this paper:
http://www.pnas.org/content/early/2010/08/16/1007944107.full.pdf+html
that the sequences looked to identify these retroviruses are glycoGag, Gag, Pol and Env (not sure if other proteins need to be made in order to complete the virion, though). I have being reading about Gag and glycoGag:
http://jvi.asm.org/cgi/reprint/68/6/3857.pdf
And I am not sure about the difference. Gag gene codes for the core of the virus, I believe. The glycoGag is a gene whose initial codon differs for the normal Gag gen, and I think codes for a second and glycosilated version of the proteins Gag and Pol.
I don’t know if both Gag and glycoGag are needed to form the virion (i.e, to form a virus able to infect), but it seems that the XMRV, because it hasn’t got glycoGag, seems to be unable to infect on its own:
(…) the hybrid nature of the XMRV genome, and the occlusion of the otherwise necessary glycogag ORF underscore the potential complementation and recombinational events that may lead to their transmission into humans. Interestingly, MLV glycogag can both increase the production of HIV-1 (11) and efficiently substitute for Nef to reestablish HIV-1 spread (20). These observations suggest a scenario in which retroviruses, MLV-related agents, and potentially, other viral agents may crosscomplement to promote coinfection and enable pathogenicity. (…)
(…)Our results demonstrated that glycoGag expression is positively selected
and essential for full spreading and pathogenic abilities (…)
Actually, as I understand, XMRV has Glycogag, with a 24 base pairs deletion, that I guess it is what prevent this protein to be functional. So here is one of the questions:
Does a deletion in the gene coding for a protein prevent the protein to be built? Or maybe it is build but it is not functional, or it is just partially functional?
Ok, I wanted to write down the origins of the different XMRV genes, and here I have some doubts too:
GlycoGag Leader (inicial codon CTG): Disfunctional or absent in XMRV? It has a 24 bp deletion that should account for its flaw…It comes from the Polytropic MLV...What is the role of this protein?
Gag (Inicial codon ATG): I think it comes also from polytropic MLV.
Pol (Initial codon??????): Aprox. first half comes from Polytropic MLV and the other half comes from Xenotropic MLV.
Env: Comes from MLV Xenotropic, and determines the XMRV tropism towards nonmouse-cells (so it cannot infect mice, unless a genetic modification is done in certain mice…).
Ok, I know this is a bit “messy”, but I still don't have the concepts very clear…
I guess that my main questions are:
Are my notes correct?
What are the actual and main differences between the discovered MLVs (including XMRV)? It seems to be the env protein, its tropism, and its infectivity capacity…
Anyone can clarify a bit this sea of confusion in which I am drowning???
Thanks!
Sergio