My Thoughts on Technology and Jamaica: HMMI develops VirScan - How Viral Peptide baits Antibodies creating Viral History from 1 drop of Blood

Tuesday, July 14, 2015

HMMI develops VirScan - How Viral Peptide baits Antibodies creating Viral History from 1 drop of Blood

“We've developed a screening methodology to basically look back in time in people's [blood] sera and see what viruses they have experienced. Instead of testing for one individual virus at a time, which is labor intensive, we can assay all of these at once. It's one­stop shopping”

HMMI Researcher Dr. Stephen Elledge commenting on their developement of VirScan

Imagine being able to determine every single virus a patient had ever been infected with from a single drop of blood?

Well, it’s now possible thanks to VirScan, a blood assay developed by researchers at HHMI (Howard Hughes Medical Institute) as reported in the article “VirScan reveals your viral infection history in a single drop of blood”, published June 4, 2015, Medicalxpress

The research was led by Dr. Stephen Elledge who works at Brigham and Women's Hospital while moonlighting at the HHMI as a researcher. Their research, published in the Friday June 5th 2015 issue of the Journal Nature, outlines a US$25 test for some one thousand (1000) permutations of the two hundred and six (206) species of human viruses.

This will allow the assayist to determine every virus a patient has ever been infected with, based on the antibodies their Immune System produces. Unfortunately, VirScan can determine when they’d been infected with those specific viruses.

It works by screening the blood using a specially designed test, based on reactions to certain antibodies from two hundred and six (206) species of viruses. Even years after the initial infection by a virus, your body will continue to produce that particular antibody to protect against future viral re-infections.

Their research holds the potential of creating a database of viral history among particular populations of humans, which is helpful in planning Public Health strategies for Governments. It also can assist in the treatment of patients as knowledge of their previous viral infection history could advise doctors what drugs might cause adverse effects on the patient.

It can also be used a test for vaccines and with an adjustment in terms o the antibodies it can detect it can also be used to test for certain autoimmune diseases, bacterial infections and Cancers.

So how exactly does this US$25 test work? Surprisingly, with the help of my favorite virus; bacteriophages!

Bacteriophages used in VirScan - How Viral peptide are bait for catching Antibodies

The researchers led by Dr. Stephen Elledge basically used bacteriophages to mimic those 206 species of viruses.

They did this by taking those know viruses and denaturing them to produced 93,000 codons from the DNA that are used to produce viral proteins. DNA molecules are structured in organized combinations of nucleotide bases called Adenine (A), Guanine (G), Cytosine (C) or Thiamine (T) in the usual helix shaped ladder-like structure.

Because of the shape of each nucleotide base, Adenine (A) can only bond with Thiamine (T) and Guanine (G) can only bond with Cytosine (C). Groups of three (3) of these nucleotide bases representing a single amino acid is called a Codon.

When several Codon are combined and decoded by mRNA within a cell's reproductive engine, the amino acids they represent and combined to represent a fragment of a viral protein molecule called a peptide.

The researchers created a nutrient solution filed with these Viral DNA fragments. Then they introduced some bacteria to feast upon the bacterial DNA fragments. The Researchers then allowed these bacteria to be infected by a certain species of bacteriophage.

Bacteriophages are special viruses that attack bacteria and are important to protecting the human digestive system against harmful bacteria as noted in my blog article entitled “Dr Bas Dutilh’s crAss discovers crAssphage Virus - How Bacteriophages can prevent Colorectal Cancer and attack other Bacteria”.

These Bacteriophages, in feasting on the bacteria, also absorbed the DNA fragments from their infected host. Their internal reproductive mechanisms used to DNA fragments and manufacture the viral peptide, which manifested on the outer protein coat of the bacteriophage virus.

Bacteriophages can display a many as one thousand (1000) peptides for one thousand (1000) permutations of the two hundred and six (206) species of human viruses, making them a super efficient way to test for multiple viruses all at once from a single drop of blood.

Knowing this, researchers then proceeded to mix the bacteriophages that had with blood samples from some five hundred and sixty nine (569) people in the United States, South Africa, Thailand and Peru. The human Immune systems produce anti-bodies that latch on to the epitopes that are embedded in the viral peptide.

Then using a chemical binding agent, they then retrieved the antibodies and some of the bacteriophages attached to them. After a more thorough washing, they basically had just the antibodies and the viral protein fragments.

Using Genome sequencing techniques, they were able to figure out which antibody encoded to which viral peptide and in turn determine the virus that infected the patient being tested. Good to note that this antibody that was present in the patient's blood may also be there as a response to a past vaccination, such as from a MMR (Mumps Measles and Rubella) vaccination.

Viral History from 1 drop of Blood - Viral History can also include Autoimmune, Bacterial and Cancer infections

Some interesting results also turned up from this VirScan test which involved some 100 million potential antibody/epitope interactions to quote Dr. Stephen Elledge: “In this paper alone we identified more antibody/peptide interactions to viral proteins than had been identified in the previous history of all viral exploration”.

Analysis of the past viral history of the five hundred and sixty nine (569) people in the United States, South Africa, Thailand and Peru revealed some interesting statistics:

1.      10 different antibodies on average were present in the blood samples
2.      Antibodies were common in Adults but not in children
3.      Patients from  South Africa, Thailand and Peru had more antibodies than those from United States
4.      HIV infected patients had more antibodies for more virus than non-HIV patients
5.      Different patients antibodies recognized the same viral proteins

As a way of testing the effectiveness of their VirScan method, they tested patients in their sample known to have HIV and hepatitis C. VirScan was able to detect the presence of these current viral infections with an accuracy of 95% to 100%, proof of its accuracy, to quote Dr. Stephen Elledge: “It turns out that it works really well. We were in the sensitivity range of 95 to 100 percent for those, and the specificity was good—we didn't falsely identify people who were negative. That gave us confidence that we could detect other viruses, and when we did see them we would know they were real”.

Based on the accuracy in identifying patients with known viral infections as well as similarity between patient antibody/epitope interactions with viral peptides, the team was able to improve their analysis methods and thus the sensitive of the VirScan assay.

At the rate at which the antibody/epitope interaction take place, Dr. Stephen Elledge estimates a two (2) to three (3) day turnaround to test one hundred (100) blood samples for all one thousand (1000) permutations of the two hundred and six (206) species of human viruses using single drops of blood instead of an entire testube sample.

Viral and bacterial vaccines can be improved via the use of VirScan as an all-in-one testing method. VirScan can also be expanded to detect bacterial infections by feeding the bacteriophages DNA fragments from bacteria.

It can also be modified to detect Cancers as well as autoimmune diseases, as the bacteriophages adopt the DNA that they consume, all from one drop of blood.

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