Naturally occurring polymorphisms of the mouse gammaretrovirus receptors

[Jemal]

This is from the lady that researches GaLV, XMRV and gibbons and got large funds from the NIH. Might be an interesting read. There's a section about XMRV on page 20, 21 and 22.

Naturally occurring polymorphisms of the mouse gammaretrovirus receptors CAT-1 and XPR1 alter virus tropism and pathogenicity
Christine A. Kozak
Received 5 May 2011; Accepted 12 July 2011

Academic Editor: Paul Jolicoeur

Gammaretroviruses of several different host range subgroups have been isolated from laboratory mice. The ecotropic viruses infect mouse cells and rely on the host CAT-1 receptor. The xenotropic/polytropic viruses, and the related human-derived XMRV, can infect cells of other mammalian species and use the XPR1 receptor for entry. The co6 evolution of these viruses and their receptors in infected mouse populations provides a good example of how genetic conflicts can drive diversifying selection. Genetic and epigenetic variations in the virus envelope glycoproteins can result in altered host range and pathogenicity, and changes in the virus binding sites of the receptors are responsible for host restrictions that reduce virus entry or block it altogether. These battleground regions are marked by mutational changes that have produced 2 functionally distinct variants of the CAT-1 receptor and 5 variants of the XPR1 receptor in mice, as well as a diverse set of infectious viruses, and several endogenous retroviruses co-opted by the host to interfere with entry.

http://www.hindawi.com/journals/av/aip/975801/

 

[Jemal]

This paper is mostly beyond my ability to understand. I found this to be a weird quote:

Although X-MLVs are able to infect all mammals, XMRV is uniquely restricted by cells of 3 species: Chinese hamster, Syrian hamster and gerbil.

Are they saying XMRV could only infect two species of hamsters and one species of gerbil?

 

[OverTheHills]

Hi Jemal,
No, I don't think they're saying XMRV can only infect some hamsters and gerbils.
The highlighted sentence says 'Restricted by' not 'restricted to' , I'm assuming they are talking about things like APOBEC3? aren't they known as restriction factors?

Hope that helps, I don't understand this level of science AT ALL.
OTH

 

[alex3619]

Hi, restriction factors restrict the virus in its capacity in some way: sometimes they destroy the virus, sometimes they just alter it a little. Bye, Alex

 

[RedRuth]

This is really interesting and much more up my street, research wise. I suppose it's basically about the on going arms race between virus and host. WRT XMRV she says These results suggest that XMRV differs from other X-MLVs in its
interaction with XPR1 receptor determinants, and also suggest that XMRV may be uniquely dependent on an as yet unidentified receptor cofactor which means it may interact with a different part of the XPR1 protein and that there may be a secondary co factor that that isn't needed by other MLVs. she doesn't say anything about host restriction factors like APOBEC or tetherin/CD317.

 

[Mark]

This is really interesting and much more up my street, research wise. I suppose it's basically about the on going arms race between virus and host. WRT XMRV she says These results suggest that XMRV differs from other X-MLVs in its
interaction with XPR1 receptor determinants, and also suggest that XMRV may be uniquely dependent on an as yet unidentified receptor cofactor which means it may interact with a different part of the XPR1 protein and that there may be a secondary co factor that that isn't needed by other MLVs. she doesn't say anything about host restriction factors like APOBEC or tetherin/CD317.

If this has grabbed your interest, RedRuth, then Kozac's earlier papers on XMRV should be of great interest too, as well as the response of some of the scientists here to them.

This one from Dec 2010 was much discussed here: the most extraordinary factor, as I recall, was that (I think) this was the study that estimated the emergence of XMRV to roughly a 30-year window, in a specific species of mouse which lives only in the area where what may have been the first ever outbreak of ME occurred - Los Angeles 1934: the time-frame and location are just right for the origin of XMRV and ME to coincide! I mention that because that connection is a good example of the sort of information that knowledgeable people within the ME/CFS community have at their fingertips, and which researchers focused on a specific discipline may lack...anyway, this research should be very interesting to you I suspect, if you haven't seen it already...

http://forums.phoenixrising.me/showthread.php?8879
http://phoenixrising.me/forums/entry.php?685-Contamination-is-DOA&bt=3652

And here's the rest of Kozac's XMRV research in PubMed:
http://www.ncbi.nlm.nih.gov/pubmed?term=kozac%20xmrv

 

[Jemal]

Hi Jemal,
No, I don't think they're saying XMRV can only infect some hamsters and gerbils.
The highlighted sentence says 'Restricted by' not 'restricted to' , I'm assuming they are talking about things like APOBEC3? aren't they known as restriction factors?

Hope that helps, I don't understand this level of science AT ALL.
OTH

Thanks for your reply OTH!
It does seem I interpreted the sentence wrong. It's the other way around: there's a few species of hamsters and gerbils that can restrict XMRV.

 

[RedRuth]

Interesting stuff. I have now found some information on host restriction factors and XMRV. Apparently both Human and Mouse tetherin/CD317 and APOBEC restrict XMRV efficiently and there doesn't seem to be any viral accessory proteins that counteract these factors (like Vpu - an HIV-1 accessory protein). This has important implications as PBMCs and all hematopoietic cells express tetherin/CD317. If XMRV is an infective Human virus it's not likely to replicate in these cells. http://www.pnas.org/content/107/11/5166.full