Is this anything?

[jimbob]

by Xinlu Wang, Fan Tu, Yiping Zhu, Guangxia Gao

Background

The zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses, including Moloney murine leukemia virus (MoMLV), HIV-1, and certain alphaviruses and filoviruses. ZAP binds to specific viral mRNAs and recruits cellular mRNA degradation machinery to degrade the target RNA. The common features of ZAP-responsive RNA sequences remain elusive and thus whether a virus is susceptible to ZAP can only be determined experimentally. Xenotropic murine leukemia virus-related virus (XMRV) is a recently identified γ-retrovirus that was originally thought to be involved in prostate cancer and chronic fatigue syndrome but recently proved to be a laboratory artefact. Nonetheless, XMRV as a new retrovirus has been extensively studied. Since XMRV and MoMLV share only 67.9% sequence identity in the 3′UTRs, which is the target sequence of ZAP in MoMLV, whether XMRV is susceptible to ZAP remains to be determined.

Findings

We constructed an XMRV-luc vector, in which the coding sequences of Gag-Pol and part of Env were replaced with luciferase-coding sequence. Overexpression of ZAP potently inhibited the expression of XMRV-luc in a ZAP expression-level-dependent manner, while downregulation of endogenous ZAP rendered cells more sensitive to infection. Furthermore, ZAP inhibited the spreading of replication-competent XMRV. Consistent with the previously reported mechanisms by which ZAP inhibits viral infection, ZAP significantly inhibited the accumulation of XMRV-luc mRNA in the cytoplasm. The ZAP-responsive element in XMRV mRNA was mapped to the 3′UTR.

Conclusions

ZAP inhibits XMRV replication by preventing the accumulation of viral mRNA in the cytoplasm. Documentation of ZAP inhibiting XMRV helps to broaden the spectrum of ZAP’s antiviral activity. Comparison of the target sequences of ZAP in XMRV and MoMLV helps to better understand the features of ZAP-responsive elements.

[V99]

These viruses do their damage even when latent. The envelope is neurotoxic, and they integrate in the promoter regions of genes, turning them on and off. They start replicating after an immune assault, but don't use reverse transcriptase to replicate.

XMRV/VP62 is a laboratory artefact, but VP42, VP35 and the ME retroviruses are not XMRV.

[bullybeef]

Don't forget JHK?

[V99]

Yep. Thanks bully.

Which is still listed as an XMRV in the Genbank. I love how they thought they could get that changed. And the Lithuanian isolate. Both of which are nothing like Coffins consensus sequence, which has no envelope gene.

[bullybeef]

I have become much more fascinated with the JHK virus.


It was never published that is was isolated from a ME patient, and it's discovery only appeared in publication 8 years after it was isolated (JHK was isolated from a ME patient in 1989 - published as a new human retrovirus in 1997 with no mention of ME. Yet Grossberg's website states there is a possible association with ME).
It has yet to be validated or replicated. In fact the silence over it is very suspect.
It was only added to Genbank last year - over 20 years after its discovery.
It's uncanny relationship the EBV and the human B-lymphoblastoid cell line.


Could it be that De Freitas and Mikovits (maybe even Alter) rediscovered the JHK virus, or variants of it? I understand the JHK virus is very small in comparison to HIV. Was this the case with Judy's isolate?

I was only looking at Grossberg's publications and he's been looking at HGRVs for sometime now (~30 years or more): http://www.ncbi.nlm.nih.gov/pubmed?term=...id=9201810


I think it was the discovery of the JHK virus which reinforced the process to belittle and profess ME as a medical myth.

[liquid sky]

I've always wondered where the samples and information from DeFrietas and her discovery are stored. It seems beyond belief that a retrovirus has surfaced in ME patients decades apart and both times the discoveries have met with such fierce opposition.

It is time to check for reverse transcriptase in patients and also move on to the tissues that were shown to be infected in the monkey studies.

[flopsy]

Rumour has it the some Defrietas samples are stored with Dr Klimas but as far as I know no one has ever confirmed this.

[V99]

JHK is a gamma retrovirus and an MLV-like virus, same as Mikovits/Ruscetti, Lo/Alter/Hanson and Hanson sequences.

They were obviously scared to publish back in the 90s and the Grossberg paper is still there. Can you imagine them trying to retract that now? Almost as blatant attempt as with the other 2 out 4 papers.

[V99]

(06-18-2012 05:05 AM)flopsy Wrote:  Rumour has it the some Defrietas samples are stored with Dr Klimas but as far as I know no one has ever confirmed this.

De Fraitus thought she had a different virus. it wasn't an MLV type, but when the CDC did their none replication study they did get GALV contamination, which is a gamma.

If Klimas has the samples - hmm well.

[fly]

I wonder if klimas will find a way of testing CBT and GET on the samples?