neurotoxicity of XMRV class viruses

G

Gerwyn

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The following comes from a paper examining the neurotoxicity of XMRV class viruses

Polytropic murine retroviruses are members of murine



leukemia viruses (MuLVs), a subfamily of the gamma retroviruses.
This is the same family as XMRV

T
he MuLV family can
be further divided depending on the type of cellular receptor utilized by the virus, which
also aVects the host range of the virus. For example, ecotropic retroviruses, which primarily
infect mouse cells, utilize the cationic amino acid transporter (solute carrier family 7 member
1, SLC7A1) protein as a receptor.
Amphotropic retroviruses, which infect a broad range of
species, utilize the phosphate transporter solute carrier family 20 member 2 (SLC20A2)
protein as a receptor.
These infect mice and a few other species

Polytropic as well as xenotropic retroviruses infect cells through the
xenotropic/polytropic receptor 1 (XPR1), a member of the G-protein coupled receptor
protein signaling pathway family [30, 31].
This is the XPRI receptor that cells must express before xmrv can infect a host

Polymorphisms in XPR1 between mammalian
species mediate the host range of xenotropic and polytropic viruses [32, 33].
The XMRV1 receptors have a different shape in some mammalian species compared to others.IXMRV will infect some mammals more readily than others>in some a small initiall exposure will lead to significant infection and in others it will take a much larger exposure or direct blood contact for example.


DiVerences between the subfamilies of MuLVs are also observed with virus infection
and pathogenesis of the CNS.

Ecotropic retroviruses can induce either intracerebral hemorrhages
or widespread spongiform degeneration depending on determinants in the ecotropic
envelope protein [34–38].
These are the mouse specific ones

In contrast, the brain pathology following infection with neurovirulent
polytropic retroviruses is more limited and primarily consists of reactive astrogliosis,
white matter microglial infection with microgliosis and microglial nodules [28, 29].
T
here
is only minimal vacuolation and only occasional neuronal death. In this regard, polytropic
retrovirus infection of the CNS has some similarities with HIV-encephalopathy.
This what a polytropic Mulv can do

Polytopic viruses arise from an endogenous ecotropic virus, recombining
with two or more non-ecotropic endogenous viral sequences (48 , 101 , 133). Each class of
endogenous retrovirus utilizes a different receptor to infect cells (Table 1).
This is very similar to the "birth" of XMRV which is polytropic in its host range of infection

Immunol Res (2009) 43:149–159

Innate immunity in the pathogenesis of polytropic
retrovirus infection in the central nervous system
Karin E. Peterson Min Du
Published
 

fingers

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....and this means.....

Gerwyn

I can't help feeling that all that is very significant, but I'm XMRV'd if I can understand it.

Any chance you could precis it for the slow people like me here?

Many thanks

Steve
 

lostinthedesert

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Thanks for this. I am still processing. Have you found any mention of viral or viral protein interaction with the trpv1 vanilloid receptor implicated in mcs? thanks again, S
 

natasa778

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This is the XPRI receptor that cells must express before xmrv can infect a host
Hi Gerwyn, one of the CROI presenters was saying that there must be another common receptor that XMRV utilises in the absence (or alongside) XPR1. They found XMRV infected cells that do not express XPR1. They are searching for the other/s co-receptors as we speak. My bet is on CCRs, esp CCR2.
 

natasa778

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ps also check Peterson et al 2006 paper "Increased proinflammatory cytokine and chemokine responses and microglial infection following inoculation with neural stem cells infected with polytropic murine retroviruses"
 

JillBohr

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Natasa, is this paper online? If not, would it be possible to add this to the library. Not that I would be able to understand but I would still like to take a look at it. Very interesting.
 

JillBohr

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Natasa, is this paper online? If not, would it be possible to add this to the library. Not that I would be able to understand but I would still like to take a look at it. Very interesting.
I apologize, I just realized it was Gerwyn that posted this. Well... you both are part of the United Kingdom.
 
G

Gerwyn

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Gerwyn

I can't help feeling that all that is very significant, but I'm XMRV'd if I can understand it.

Any chance you could precis it for the slow people like me here?

Many thanks

Steve
Hi Fingers

XMRV is a MULV class virus

XMRV although described as xenotrophic (cant infect mice but can infect certain other species).It behaves as if it is polytrophic(infects mice and every other species with a certain type of cellular receptor(XPR1)

Polytophic MuLVs are directly neurotoxic and cause the same range of neurocognitive symptoms that are reported in patients with ME/cfs (described in the paper as encephalopathy)

is that Ok
all the best

Gerwyn

P.S for future reference would a summary at the start like take home messages be helpful?
 

JT1024

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Gerwyn,

Thanks as usual for your continued research findings. In answer to your question regarding a summary or "take home messages"... I think that is an absolute YES!

I've directed many people to this site because of its exceptional content but many are intimidated by the level of some of the discussions. CFS/ME hits a broad spectrum of people and not all can understand or discuss topics at your level!

Just like there's an abstract at the beginning of most research articles I've seen, perhaps something similar would be helpful....just a distillation of they key points.

Thanks again for all you do!

~ JT
 

lululowry

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Thank you Gerwyn for the summary! And YES, it would really, really help to have similar summaries included with research articles for those of us who aren't as scientifically literate.