XMRV and HIV/AIDS: Superinfection

Knock knock.

Whos there?

Not XMRV in African blood donors or HIV/AIDS patients.

Absence of detectable xenotropic murine leukemia virus-related virus in plasma or peripheral blood mononuclear cells of human immunodeficiency virus Type 1-infected blood donors or individuals in Africa.

This is the third study not to find XMRV in HIV/AIDS patients. HIV/AIDS patients have every other pathogen under the sun at higher rates than healthy people. Except XMRV? Uh huh. Right. There is simply not enough evidence to believe XMRV is a real human pathogen, much less that it is the causative agent in a given disease, even less so with this apparent lack-of-connection on top of it.

'Certain groups of people' clinging to XMRV-->anything are explaining this lack-of-connection by arguing that it is possible HIV-1 infection actually prevents XMRV infection, and thats why XMRV isnt found in HIV/AIDS patients.

Yes, that is possible.

But then again, anything is possible if you have no idea what you are talking about, youre just making shit up, and you are arrogant enough to think your GoogleU degree means something*.

What these 'certain people' are confused about is something called superinfection.

Superinfection is when one cell is infected with two different viruses. As in, HIV-1 Subtype B and HIV-1 Subtype C, or HIV-1 Subtype A and HIV-2. One person who was independently infected with HIV twice, and then has any number of cells also infected twice.

This 'normally' doesnt happen, because HIV-1 pisses on the fire hydrant. When a cell is infected with HIV-1, various HIV-1 proteins will downregulate the HIV-1 receptor (CD4) on the infected cell. Its HIV-1s way of saying 'THIS IS MY FORT! NO ONE ELSE ALLOWED! MINE!!!!'

If someone already has a well established HIV-1 infection, cellular targets of HIV-1 infection are either a) dead or b) already infected, so it becomes more difficult for a different kind of HIV-1 to gain a foothold and infect that person a second time with an alternative genotype of HIV-1.

Thats not to say that it is impossible. Yes, we have HIV-1 'Subtypes', but those I think will ultimately disappear. Thats because people can get infected with two different subtypes, and then you inevitably get superinfection, and then we have viral sexy time, and then we get babby viruses that are part one thing, part another: circulating recombinant forms. No more subtypes.

Guards against superinfection (pissing on the fire hydrant) come from the viruses themselves, like downregulating receptor. HIV-1 uses CD4 and CCR5/CXCR4. XMRV uses XPR1. There is no scientific evidence that infection with one virus impacts infection of another. Nothing. Nor has any putative connection been proposed by anyone, anywhere.

That is, 'anywhere' except message boards, and 'anyone' except random people on the internet finding an article above their heads on 'superinfection' that they dont understand, but are too uneducated to realize they dont understand, and too arrogant to ask for help.

* NOTE: Asking questions like "Can HIV-1 infection inhibit XMRV infection?" is not stupid. Aggressively asserting that "HIV-1 infection inhibits XMRV infection" while ridiculing scientists for 'wasting time looking' for XMRV in HIV-1(+) patients is stupid.

More like this

Even though XMRV has joined the choir invisible (rather than the list of human pathogens), scientists all over the world have still been publishing on it. Some of these studies were started before XMRVs demise, some were initiated to figure out how/why XMRV died, and some were done just to be on…
Vpu has kinda been my accessory protein of choice here at ERV, but its not the only one with a super cool evolutionary history and super cool evolutionary implications. Another particularly fun one is Nef. This eeeeeeeety bitty HIV-1 protein (27 kDa) has a lot on its plate. Contrary to the '…
This is a repost from the old ERV. A retrotransposed ERV :P I dont trust them staying up at Blogger, and the SEED overlords are letting me have 4 reposts a week, so Im gonna take advantage of that! I am going to try to add more comments to these posts for the old readers-- Think of these as '…
Two things I didnt intend on writing about on ERV more than a few times, but turned into repeat guests: XMRV and Vpu. Theyve finally come together. Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors Know how I was talking about intrinsic…

As you said previously...it is too late.

The crap correlative and crappier crap causative theory are now woven into the identity of the "community of sufferers".

There is no limit to mental contortion in the effort to defend a definition of self.

This is just the early stage, wait for the kind of self delusion that blames fossils on satanic deception.

By Prometheus (not verified) on 22 Nov 2010 #permalink

I thought you had abandoned this subject? What a weak person you are

Im talking about XMRV and HIV, not XMRV and CFS. Apparently you didnt read this post, or the post you are referencing, any more than youve read anything on ERV. Not your fault, though. Its the 'fog', right?

You really should lurk moar.

Can a person infected with a retrovirus become infected with another retrovirus?
Did the studies mentioned check for presence of XMRV in the blood only?
I'm not yet convinced by the XMRV link but there is definite immune dysfunction aa well as other systemic invlolvement in ME and CFIDS. The psychological and/or deconditioning model only serves the governments' politico-economic purpose whilst the patients are left with lies and mistreatment.

Well, you would think this would put a major hole in the hypothesis that XMRV is the causative agent of (fill in human ailment). If HIV-positive people don't have XMRV in their blood, then it's not likely to be infectious.

About the only logical argument (barely) that I've heard in defense of XMRV as a causative agent for human disease is that it is somehow (magic?) restricted to the US, which would explain (in a rather unspecified fashion) why researchers looking for it in the UK, Europe, Africa etc. have been unable to find it.

As appealing as this hypothesis may be, it still fails to explain why XMRV is averse to traveling outside the US. Perhaps it subtly alters its host's nervous system to make it fearful of leaving its home and traveling long distances?

A simpler explanation, however, is that the laboratories finding high percentages of XMRV are making some sort of error. In fairness, it could also be that the labs failing to find XMRV are not using the proper technique.

Only time will tell.

Prometheus (the other one)

This (aside from your general personal awesomeness) is why I come here, Abbie. HIV pisses on the fire hydrant? AWESOME. I had no idea viruses could do this. I'm always learning something new here.

Also, vaguely related: Just gave blood today, and what I thought I remembered from last time is accurate: They've got posters and handouts explaining that CFS patients should not donate because XMRV is a possible cause.

The other Prometheus: Huh? Not sure what you mean. Researchers in several countries (e.g. UK, Sweden, Spain and Japan) have been able to find XMRV. Not all of the study groups in the aforementioned countries that have been set to find it, but some scientiests nonetheless. It's definitely not limited to the U.S.

" HIV/AIDS patients have every other pathogen under the sun at higher rates than healthy people"

not reactivated Epstein Barr.

By thomas_bernhard (not verified) on 22 Nov 2010 #permalink

The finding in Spain appears to be a journalistic error (http://www.prohealth.com//library/showArticle.cfm?libid=15703)
Outside of the USA and excluding studies based on the commercial WPI/VIP Dx test I seem to remember (damn fog) positive studies from Japan (bloodbank), China (prostate cancer), Germany (respiratory tract). The results from Belgium, Norway, UK, ... are all (?) based on (a licensed) VIPDx' testkit, lot of them still on the XMRV PCR, but more recently XMRV co-culture and MLV PCR. The studies by dr. Ilia Singh should get published before the end of the year, and hopefully the one by Ian Lipkin too. Wait and see, whatever the outcome will be.

HIV/AIDS patients have every other pathogen under the sun at higher rates than healthy people

not reactivated Epstein Barr.

Wait, what? HIV+ status is a major risk factor for reactivated EBV. Did you make a reading error?

to say xmrv cannot co-exist with another retroviral infection is totally false! then why are there numerous cfs/gwi patients who do test positive to xmrv at the proper testing labs and these same patients also test positive to mycoplasmas which has been proven to link to hiv and these cfs/gwipatients also carry 45% of the hiv virus envelope found by garth nicolson well over 10 years ago and still the cdc/nih and world agencies still are downplaying the seriousness of cfs/gwi as bona-fide serious infectious diseases! cover-up is exactly why and the full truth of hiv/cfs/gwi must be told...man made infectious diseases are exactly what these 3 illnesses are, syntetic and not naturally occuring... sincerely aidan walsh southampton, u.k.

By aidan walsh (not verified) on 22 Nov 2010 #permalink

Man, I hope aiden walsh sticks around; he seems fun. Arnie isn't the only one that loves chew toys.

Thats for real, Cain. No spam in the form of links or name url or nuthin. That is some pure stuff-- dont drink too deep, if he comes back!

I think I've missed the discussion on HIV and XMRV interacting. Sounds like it's no loss.

I agree with the other Prometheus (?) that this is surely explained by some testing error on the part of either the positive labs, or the negative labs. There are some tit-bits in the new WSJ piece... maybe we'll know in another years time:

http://online.wsj.com/article/SB100014240527487042439045756307001117294…

ERV,
In addition to CD4 receptor, HIV-1 infection apparently needs the CCR5/CXCR4 chemokine binding co-receptors you mentioned in order to sucessfully claim the fire hydrant. Certain chemokines and cytokines profiles are rumored to be different in HIV patients compared to in a certain group of patients with unexplained illness associated with XMRV which shall not be named here.

Theoretically, if this is so, could chemokine/cytokine differences affect the territorial status of the fire hydrant in question and interfere with HIV infection in these cases?

Other Prometheus,

So you're saying that XMRV could be acting like that fungus that controls the behaviour of infected ants? You may be on to something here. ;P

By Poodle Stomper (not verified) on 23 Nov 2010 #permalink

Aiden,

Sounds interesting. Could you expand on this link of mycoplasmas to HIV?

By Poodle Stomper (not verified) on 23 Nov 2010 #permalink

Indeed Lilith...her intelligence is to be admired. But what really makes her shine is knowing that intellect apart from humility is but an exercise in mental masturbation.

How dare you!? My University of Google degree is priceless.

By theshortearedowl (not verified) on 23 Nov 2010 #permalink

I am still very interested in the results of phase II from the Blood Working Group. Should put the controversy to an end, although, in the case it turns out to be contamination, I am sure there will still be some people concluding that there must be some kind of giant conspiracy going on. Oh well...

Although the results of phase II may be presented earlier, I believe they are scheduled to be released on 12/14. Mark that date...

There have been some concerns about the design of the BWG study. I have heard they are using synthetic clones to calibrate against. This clearly is not the most reliable method of detecting retroviruses. We only need to refer to past studies involving the search for HIV using synthetic clones.

http://www.mdpi.com/1999-4915/2/11/2404/

@Lilith

While 'spiked' samples were used during phase I, the BWG is using samples that are "confirmed positive" by WPI in phase II. Besides, calibration is not really an issue, as the question really is whether WPI/Mikovits AND FDA/Lo (this is important) can 'identify' the "XMRV positive" patients from the pool of blinded samples, and also if the WPI or FDA can 'identify' the other, 'fresh' CFS samples from that pool.

If these two labs can do these things, nobody can really argue that there's nothing there, and if they can't do these things, nobody can really still argue that the original WPI/FDA findings are valid. Calibration doesn't enter the equation.

Oh, and BTW:

The methodology that Singh is proposing seems like circular reasoning with regard to using 'known positives'. There are no truly confirmed positive patients as of yet; that is what scientists are actually trying to determine. What better way to investigate this than to send 'fresh' samples from 'fresh' patients to the labs that are claiming they can routinely find it?

Singh's argument about not using deintification labs also seems strange. Luckily the BWG and Lipkin are doing this part different and seem to be truly blinding the samples from the testing lab(s). Lipkin has this year published a paper (partly) about the same subject as the recent Singh paper, and he has (IMO convincingly) argued against the methodology that Singh is proposing:
http://cii.columbia.edu/documents/MicrobeHunting_MMBR.pdf
See p. 369

@ERV, recognizing the depth of your understanding of XMRV/MLV science, this may be a case of bringing coal to Newcastle. But just in case⦠this information is from Dr Singhâs recently published 2010 patent application on XMRV. You can read a summary here: http://www.facebook.com/#!/notes/xmrv-global-action/dr-singhs-xmrv-pate… , with links to the original patent.

Excerpts:

"[0003] The present inventors discovered that Xenotropic murine leukemia-related retrovirus (XMRV) has a strong link with human cancer, including prostate cancer and breast cancer.

â¦. 178 cases of breast cancer were examined for the presence of XMRV using the described methods. Approximately 25% of breast cancers contained either XMRV proviral DNA sequences or XMRV proteins. The XMRV proteins were seen exclusively in the malignant breast epithelium (Figure 11).

The ability to detect XMRV in semen is also important to determine possible routes of XMRV transmissionâ¦.XMRV DNA or RNA was found in approximately 7% of all (semen) samples tested, indicating that XMRV is present in semen obtained from otherwise healthy men who are not known to have prostate cancer or chronic fatigue syndrome, or other XMRV-associated conditions. This finding has important implications for viral spread, and tests for detection of XMRV in semen have an application in testing donor semen samples used in fertility clinics.

The ability to detect XMRV in cervical fluids as described here has allows for determining a possible route of spread of virus, including spread from mother to infant during childbirth, and has important implications for public health."

Looking forward to the discussion.

By Science_based (not verified) on 25 Nov 2010 #permalink

Science-based-- Are you illiterate, or are you just plain lazy? There are already people talking about your 'breaking news' in this thread.

If you are 'looking forward to the discussion' you might start by fucking reading the discussion already in progress.

XMRV:
We found XMRV DNA in 6% and XMRV protein expression in
23% of prostate cancers.

http://www.rense.com/general67/propioni.pdf
Propionibacterium acnes:
Materials and Methods: Prostatic tissue from 34 consecutive patients with prostate cancer was cultured to detect the presence of bacterial agents. ...
Results: The predominant microorganism detected was Propionibacterium acnes, found in 35% of prostate samples. A significantly higher degree of prostatic inflammation was observed in cases culture positive for P. acnes (p = 0.007).

Just to say thanks ERV for the skeptical view to this XMRV business. I share 'that illness' with many who think you are Voldermort, or something. You are, however, awesome (and if you are Voldermort even more so). I just think a lot of the 'community' have become desperate for an explanation so are grasping at straws, hence why they're acting like idiots with the name calling and such.

Patent application =/= published positive study.

And that Proprioni study confuses me - it's all about bacteria, not viruses?!

I think it's time mouse mammary tumour virus or TTV had their share of this controversy.

There is one major problem with your conclusion: all three of the studies you cite are linked by their failure to detect XMRV in both patient and control groups. Not a single instance. Zero. Zilch. This, after Harvey J. Alter and the FDA/NIH/Harvard study definitively showed that XMRV and MLV-related viruses can be found in both patient and control groups.

Failure-to-detect studies clearly indicate a problem with the methods, even if the researchers believe they are following protocol. Harvey J. Alter and the FDA/NIH/Harvard study found that a family of MLV (read: XMRV-related) viruses is at play, not a single, specific, xenotropic MLV strain. XMRV has simply taken the name for what is now a broader study of infectious MLV-related viruses, many of which cause AIDS like syndromes in mice. Their inefficiency at infecting human CD8 cells may well be indicated by the considerable 10-15 year disease progression timeline found in many adult CFS patients.

Again, your conclusions about XMRV and HIV are misplaced given the studies' complete failure to detect even a single instance of XMRV in both patient and control populations after the Harvey J. Alter FDA/NIH study already definitively showed that XMRV and MLV-related viruses are in the blood of a considerable number of patients and controls.

@Mark

Wow, we're lucky you're not a scientist. Saying the Alter/Lo study "definitively showed" that XMRV and MLV-related viruses are in the blood of patients and some controls TWICE, doesn't make it so.

The one thing that has been "definitively showed" by Alter/Lo and Mikovits is that they can "find" XMRV in a patient they have themselves pedigreed (by PCR, culture AND serology) as XMRV negative (see the results of phase I of the Blood Working Group).

If "failure-to-detect studies clearly indicate a problem with the methods", then we are clearly lost. Any quack could then "find" something new and could claim that those other scientists were clearly just having problems with their methods.

In a week, the BPAC will meet, and we will (hopefully) see whether the WPI and Alter/Lo can detect the virus in blinded AND freshly collected samples. It seems like you have already made up your mind, so what will you conclude if WPI and Alter/Lo cannot detect XMRV in both CFS patients and (the same) controls?

For anyone interested, there's a 'webinar' from the Blood Working Group's investigation into XMRV tomorrow:

https://www1.gotomeeting.com/register/985931313

I'm really interested in this stuff, but never seem to get around to watching these discussions. I'm going to try to catch this one.

The results from the Blood Working Group were a disappointment, to say the least.

It was known beforehand that Mikovits would collect only four positives, which in itself was a logical choice given the objective of phase II. However, I was under the impression that they would include more controls and, more importantly, some independently collected CFS samples. As it is, the results are not statistically significant at all...

Still, with Mikovits explaining bad PCR results (e.g. again a positive result on a pedigreed negative control) away with some strange excuse about not really being into PCR, and also with her call for longer culturing of samples than previously reported, it certainly doen't look any better for her camp - despite the passioned but not very convincing words by Alter.

Thanks for the update, RRM!
Interesting Mikovits isnt interested in PCR (modern, standard, quantitative technology) but is all up in 'culturing' (outdated, virtually unused protocol in the modern world, no means of quantifying the result-- strictly YES/NO protocol). Heh. "IF IT STAYS IN OUR LAB LONG ENOUGH, IT PRODUCES VIRUS!"

Also interesting Alter is 'passioned'. I know Im not the only one 'underwhelmed' with the 'sequences' they uploaded (they just put up a whole six more! SIX!). He found endogenous MLV. His stuff was contaminated, he used inappropriate controls, and ignored the advice of reviewers. Good lesson in 'What not to do' for us young uns.

It does seem that the pro-XMRV researchers are all emotionally involved, and think CFS patients have been badly treated. I think they're right, but it could be affecting their judgement.

The drips I've read on-line about the BWG results sound really odd. Certain brands of PCR machine were able to detect XMRV in samples when others could not. The WPI and CDC both detected XMRV in the blood of two of the four patients, but only from bloody taken on days 2 and 4, not 1 and 3.

I'm hoping we'll get a cogent explanation of what it all means tomorrow, but it's possible this wont happen.

I missed most of the presentation, and didn't really understand what I saw. It seemed to be much more focused upon finding a quick, cheap and reliable test for the blood supply than sorting out the possible link with CFS or PC.

There have been a string of papers on contamination, with McClure seeming to now think that her positive prostate cancer results were due to contamination. Also a very forthright dismissal of the link between CFS and XMRV by researchers here: http://wellcometrust.wordpress.com/2010/12/20/chronic-fatigue-syndrome-…