New test uses a single drop of blood to reveal entire history of viral infections

[Bob]

New test uses a single drop of blood to reveal entire history of viral infections
The Guardian
4th June 2015
http://www.theguardian.com/science/...-to-reveal-entire-history-of-viral-infections

Extract:

The $25 (£16) test draws on advances in synthetic biology and rapid gene sequencing to analyse more than 1000 strains of human viruses in one pass. Until now, most tests have looked for only a single virus at a time. Elledge estimates that the latest test, called VirScan, can process 100 samples in two to three days.

 

[Simon]

Works by engineering mutant viruses that display bits of all known human viruses - sort of wide-ranging mimic - and then seeing if the blood samples have antibodies that bind these viruses

The test exploits the fact that the immune system makes antibodies to fight viruses whenever the body becomes infected. These antibodies can live on in the bloodstream for years and even decades.

To develop the test, Elledge engineered batches of harmless viruses to carry bits of proteins from human viruses on their surfaces. In total, they carried proteins from more than 1000 strains of the 206 kinds of viruses known to infect people. Antibodies use these protein fragments to recognise invading viruses and launch their attacks.


When a droplet of blood from a patient is mixed with the modified viruses, any antibodies they have latch on to human virus proteins they recognise as invaders. The scientists then pull out the antibodies and identify the human viruses from the protein fragments they have stuck to.
read the full article

Science paper: Comprehensive serological profiling of human populations using a synthetic human virome
Abstract
The human virome plays important roles in health and immunity. However, current methods for detecting viral infections and antiviral responses have limited throughput and coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antiviral antibodies using immunoprecipitation and massively parallel DNA sequencing of a bacteriophage library displaying proteome-wide peptides from all human viruses. We assayed over 108 antibody-peptide interactions in 569 humans across four continents, nearly doubling the number of previously established viral epitopes. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Although rates of specific virus exposure were heterogeneous across populations, antibody responses targeted strongly conserved “public epitopes” for each virus, suggesting that they may elicit highly similar antibodies. VirScan is a powerful approach for studying interactions between the virome and the immune system.

 

[L'engle]

Does anyone know if the viruses commonly present in PWME are in the 1000 viruses scanned?

 

[Jonathan Edwards]

Maybe we should put in a grant application to do this test on 200 patients and 200 controls from the ME Biobank, with blinded samples (that's $10,000 of tests but that's not a big deal). The Biobank needs using, or will do fairly soon. I have some slight technical reservations about the methodology but it is likely to be reasonably robust as a screen.

 

[Kati]

Maybe we should put in a grant application to do this test on 200 patients and 200 controls from the ME Biobank, with blinded samples (that's $10,000 of tests but that's not a big deal). The Biobank needs using, or will do fairly soon. I have some slight technical reservations about the methodology but it is likely to be reasonably robust as a screen.

Music to my ears. How about an international study to assess similarities and differences?

 

[Jonathan Edwards]

Music to my ears. How about an international study to assess similarities and differences?

Why not?

 

[shannah]

Maybe we should put in a grant application to do this test on 200 patients and 200 controls from the ME Biobank, with blinded samples (that's $10,000 of tests but that's not a big deal). The Biobank needs using, or will do fairly soon. I have some slight technical reservations about the methodology but it is likely to be reasonably robust as a screen.

Since this test seems to meet with your approval @Jonathan Edwards , I think this is wonderfully productive idea. Providing the grant application is timely, it could yield some rather quick results that could be enlightening.

 

[Bob]

Maybe we should put in a grant application to do this test on 200 patients and 200 controls from the ME Biobank, with blinded samples (that's $10,000 of tests but that's not a big deal).

We might be able to raise that in a crowdfund within a few weeks. If getting a grant is a potential roadblock.

 

[Bob]

Maybe we should put in a grant application to do this test on 200 patients and 200 controls from the ME Biobank, with blinded samples (that's $10,000 of tests but that's not a big deal). The Biobank needs using, or will do fairly soon. I have some slight technical reservations about the methodology but it is likely to be reasonably robust as a screen.

I can't see any reason not to do this, but just a note is caution - screening for viruses has been carried out regularly, with no conclusive results, so perhaps we shouldn't expect any consistent results. But the results from 200 patients and controls might throw up some interesting surprises nevertheless.

Edit: Actually, please ignore that pessimistic comment - I got confused and thought the test was for only 100 viruses, not 1000! That scale of testing has never been carried out on ME patients - nowhere near it! Testing for 1000 viruses on 200 patients could be very interesting indeed! It might also be interesting to look for antibodies that we don't carry, compared with controls, as well as those we do carry. (Faulty immune systems and faulty B cells may not provide the correct antibodies, in enough quantities, to order?)

 

[Esther12]

Possible that reduced social contact will mean reduced number of infections?

Could being run-down (for all manner of reasons) mean that you're more susceptible for infection?

I have next to no idea about viruses, but am just wondering what sort of control group would be best to compare with CFS patients to see if there is anything particularly unusual about CFS patients and viruses.

 

[Forbin]

Seems like it would be a good idea to screen patients who were involved in one of the recorded outbreaks to see if they share one or more of the specific strains of influenza virus in existence at that time. Of course, I imagine that the test can only detect strains that are known to have existed. I don't suspect that they can know of every low prevalence mutation.

 

[Bob]

Some more info here...

$25 blood test identifies any virus you've ever had
WIRED
4th June 2015
http://www.wired.co.uk/news/archive/2015-06/04/virscan-tests-for-all-human-viruses

Note the comment about "chronic fatigue" in the extract below; They're thinking what we're thinking. (Stephen Elledge, quoted below, of Harvard Medical School, is the co-author of the Science paper. And Tomasz Kula, quoted below, is a graduate student working in Elledge's lab.)

Extracts (my bolding):

So far VirScan has delivered accurate results, with almost 100 percent sensitivity for HIV and Hepatitis C in a small trial of people known to have those viruses. "We didn't falsely identify people who were negative," said Elledge. "That gave us confidence that we could detect other viruses, and when we did see them we would know they were real."

The test does have its shortcomings, however. Although it performed very well in the HIV and Hepatitis C studies, when tested against a wider pool of nearly 600 blood samples Chicken Pox was identified in only 25-30 percent of people. "That's much lower than you'd expect," Tomasz Kula, a graduate student working in Elledge's lab, told WIRED.co.uk."Often times people are vaccinated for it or had it when they were very young, and it wanes over time. So we know we're not the best when it comes to this."

...

Although the test is not yet ready to be commercialised, the team hopes it can continue to be used in research now.

"We think we can use this to look at correlations between more complex diseases," Kula tells WIRED.co.uk. He suggests that MS or chronic fatigue could be investigated further using VirScan -- both disorders might have underlying viral triggers not yet identified. We want to look at a population of patients with a particular disease and pick out past and ongoing exposures."

 

[Bob]

Another article with perhaps a tiny bit more background...

In the extract that I've quoted below, it says that they're also using the technique to look for certain auto-antibodies associated with cancer. But it's not clear to me exactly what they are referring to...

VirScan reveals your viral infection history in a single drop of blood
Medical Xpress.
4th June 2015
http://medicalxpress.com/news/2015-06-viral-infection-history-blood.html

Extract:

Elledge says the approach his team has developed is not limited to antiviral antibodies. His own lab is also using it to look for antibodies that attack a body's own tissue in certain autoimmune diseases that are associated with cancer. A similar approach could also be used to screen for antibodies against other types of pathogens.

 

[alex3619]

When we lose seroconversion, and this happens a lot in ME and CFS patients, then we lose the antibodies. Many of us test positive at one point then negative after that. We do not know why this happens, except that its probably a B cell issue. In this case the test in this thread will give a false negative. There is also the issue of low affinity antibodies, I am not sure how this test will go with those.

 

[anciendaze]

While I would also like to see what this test shows about ME/CFS patients in the biobank, I want to add a caution about relying on this for individual patient tests rather than for statistical associations in a group. I would also like to see results stratified w.r.t. to time since onset, because we now have evidence some type of immune exhaustion sets in after three years.

The caution expressed above concerning chickenpox may be highly relevant to ME/CFS because VZV virus remains latent in places like dorsal root ganglia for years, and is not really found in peripheral blood between acute infection and appearance of "shingles" at some uncertain future date.

 

[Mark]

The prospect of a quick, cheap, yet well-designed study using this test sounds extremely appealing to me. Patient selection and profiling would be a very important issue indeed of course. I wonder if it might make sense to try to compare some subgroups within the study? Be able to see how viral load (and virus types) vary with degree of severity (measured somehow ???) and case definitions? I guess you can't go too far with this or you lose statistical power, but I don't really understand the limitations on this aspect of study design, are there any rules of thumb on how far one can go with sub-studies? (And btw the implications of assessing the stats for over 1000 strains sound hairy, but I guess we can handle the necessary error-correction here?).

 

[Bob]

The information gained from such study would be useful for the biobank to include in its own records, if appropriate data-privacy permissions are sought, as the results may potentially help to create useful subgroups for any other future studies using the biobank samples.

 

[mango]

Science paper: Comprehensive serological profiling of human populations using a synthetic human virome

Interesting to see Suzanne D. Vernon's name and Solve ME/CFS Initiative among the authors

 

[alex3619]

While we are not getting any richer the costs of many biomedical tests seem to be declining as fast as computer costs. So I expect this will not be the only test we can consider doing some kind of study with. Just maybe the first.

 

[voner]

Interesting to see Suzanne D. Vernon's name and Solve ME/CFS Initiative among the authors

my guess is that the SolveME/CFS initiative supplied samples from their bio bank? it seems that almost all the other authors are from university-based research institutions.