XMRV characterisation

[RustyJ]

Not sure if this is new or what it means. Cheers

Full Text:
http://www.liebertonline.com/doi/abs/10.1089/hum.2010.063?url_ver=Z39.88-2003&rf

Human Gene Therapy - Characterization of retroviral and lentiviral vectors pseudotyped with XMRV envelope glycoprotein
To cite this article:
Toshie Sakuma, Suk See De Ravin, Jason M Tonne, Tayaramma Thatava, Seiga Ohmine, Yasuhiro Takeuchi, Harry L Malech, Yasuhiro Ikeda. Human Gene Therapy. -Not available-, ahead of print. doi:10.1089/hum.2010.063.

Retroviral and lentiviral vectors are effective gene delivery vehicles which are currently evaluated in clinical trials. Variations in the viral envelope (Env) glycoproteins, which are used to pseudotype retroviral or lentiviral vectors, can alter the vector performance, including the stability, titers, host range and tissue tropism. Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a novel human retrovirus recently identified in patients with prostate cancer. XMRV targets XPR1 cell surface receptor, which is expressed in a broad range of human tissues including hematopoietic stem cells. Pseudotyping with XMRV Env would allow targeting of XPR1-expressing tissues. Here, we characterized the XMRV Env-pseudotyped retro- and lenti-viral vectors. Although HIV and MLV vectors were poorly pseudotyped with the wild type XMRV Env, replacement of the C-terminal 11 amino acid residues in transmembrane domain of XMRV Env with the corresponding 6 amino acid residues of amphotropic MLV Env (XMRV/Rampho) significantly increased the XMRV Env-pseudotyped HIV and MLV vector titers. The transduction efficiency in human CD34+ cells using the XMRV/Rampho-pseudotyped HIV vector (10-20%) were comparable with that achieved using the same infectious units of VSV-G pseudotyped (25%) vector, thus the modified XMRV Env offers an alternative pseudotyping strategy for XPR1-mediated gene delivery

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[George]

from Online Ahead of Editing: May 27, 2010 but I don't remember seeing it anywhere before. Good one RustyJ!

Pseudotyping with XMRV Env would allow targeting of XPR1-expressing tissues.

It looks like they are interested in XMRV for possible Gene thearpy. The XPR-1 receptor is basically the key master for, I think it's, 83% of human cell types. So XMRV could get into a host of cells that other Lenti and Murine viruses couldn't reach.

 

[RustyJ]

These guys are from the Mayo Clinic

 

[George]

Smart guys, really smart guys. . . but I got to tell you after reading the paper I think they're smokin' crack up there. They are talking about coring out HIV, XMRV and several MLV for Gene therapy. Sometimes I think human arrogance is going to just wipe us the heck out.

 

[alex3619]

Hi

Something else just occurred to me. If you use genetically modified XMRV to target the same tissues as infective XMRV, you can take antiviral genes straight to where they are needed. It will be ironic if the cure for XMRV finally turns out to be genetically modified XMRV.

Bye
Alex

 

[George]

Hi

Something else just occurred to me. If you use genetically modified XMRV to target the same tissues as infective XMRV, you can take antiviral genes straight to where they are needed. It will be ironic if the cure for XMRV finally turns out to be genetically modified XMRV.

Bye
Alex

Ain't that the truth! (big grins) Which is part of what they are talking about with coring out the HIV, HIV cored will target the exact same cells and act in, mostly, the same manner allowing them to watch disease pathogenisis and to target the infected cells with precise therapy's. Sounds absolutely brilliant.

But the thought of getting injected with a hollowed out retrovirus with a bunch of whatever they think will help just makes me tuck my tail and twitch my ears!

 

[dschlindwein]

Could it be that gene therapy experiments conducted in the early days of gene therapy (early 1970s?) are what got a retrovirus related to MLV into the human population? Or am I exposing my extreme ignorance?

 

[George]

Could it be that gene therapy experiments conducted in the early days of gene therapy (early 1970s?) are what got a retrovirus related to MLV into the human population? Or am I exposing my extreme ignorance?

No it's not possible. (grins) Ask any question ya want around here, you'll have a heck of an education in no time. If ya want to know the why it can't work that way you can look at my blog on "mouse theory" or read some of the older posts in the XMRV thread. The numbers don't add up for a 70's transmission unless it's causually infective and then it would have to be released in the mid to late 80's to have the current numbers. Most likely it entered the population sometime before 1920 if it's like other retroviruses.

 

[anciendaze]

Could it be that gene therapy experiments conducted in the early days of gene therapy (early 1970s?) are what got a retrovirus related to MLV into the human population? Or am I exposing my extreme ignorance?

Some people were infected earlier. If I am not one, I'm pretty sure I know some. If you read 19th century papers on neurasthenia, I think you will share my suspicion that this was a manifestation of something very similar -- at a time when viruses remained unknown and bacterial cause of disease was still debated. The outbreaks people have traced appear to be combinations of new varieties and new target populations. You could liken this to outbreaks of influenza, though the core genome of XMRV is much more stable.

The wild card in XMRV right now is mutation inside host cells, caused by defenses against retroviral infections, and possible recombination with sequences from host cells or coinfecting pathogens. Researchers doing what it may well be doing would be required to operate with crippled virus inside level 4 containment facilities. Nature need not obey human rules.