Test unravels history of infection

US researchers claim to have developed a single test
that is able to identify past exposure to every known
human virus infection, using a drop of blood.

The technique decodes the infection history imprinted in
our immune response.
The scientists hope that the test will eventually provide
important insight into how viruses contribute to
development of a range of diseases.
The work was published in the journal Science.
During a virus infection, your immune system generates
antibodies designed to fight the virus. Each antibody
recognises a tiny fragment of the virus and their
interaction is very specific - they fit like a lock and key.
Virus-specific antibodies can be long-lived; often
persisting many years after an infection has disappeared.
So, your antibody repertoire represents a historical record
of all of the viruses that have infected you.
This immunological catalogue has been used for years to
identify past virus exposure, but the diagnostic tests
routinely used have been limited to one, or at most a
few, different virus strains.
Discovering connections
Prof Stephen Elledge from the Harvard University Medical
School US, who led the research team, told Science in
Action that the new technique will overcome this
limitation: "You can ask questions about all viruses
rather than have to do things one at a time, so it allows
you to discover connections between different
populations or different diseases amongst groups of
people.
"Now that we can look at all viruses, it's a complete
game-changer."
Researchers have been working out the genetic sequence
- the blueprint - of all human viruses for many years.
The team used this information to generate a pool of
bacteriophage - viruses that grow easily in the laboratory
- with each bacteriophage expressing a tiny fragment of
this human-virus blueprint on its surface.
Antibodies present in a drop of human blood could then
be used as bait to go fishing in this phage pool - only
bacteriophage that express protein fragments recognised
by the antibodies in the blood sample will be caught.
Sequencing the bacteriophage DNA reveals the human
viruses that an individual has been exposed to.
The team used their test to interrogate sera obtained
from more than 500 people of different ages and living in
different global locations.
The data showed that the number of virus infections
detected in people increased during life.
The study also suggested that those living in the US
were exposed to fewer infections than people living in
South Africa, Thailand or Peru.
"We don't understand why that is. It could be something
to do with the different strains of the virus and our
inability to detect them, or it could be something to do
with the structure of the population, the sensitivity of
the population [to infection] or practices in the country",
commented Prof Elledge.
The greatest number of virus infections that were
detected in any single individual was around 25, but the
average number was only 10.
Prof Elledge thought that this was because some
individual virus protein fragments can represent many
related viruses.
Strengths and weaknesses
Commenting on the significance of the new technique
Will Irving, professor of virology at the University of
Nottingham said: "It is a technology which is probably
best applied on a population-basis rather than an
individual patient basis.
"Whilst its accuracy in defining who had HCV or HIV
infection could be massaged up to very respectable
levels, I'd be nervous about using it as a diagnostic test
to see if an individual patient has HIV infection.
"However, it will be a fabulous tool for looking at virus-
disease associations which are speculative, or even
currently unknown. For example, primary biliary cirrhosis
(PBC) has been reported, controversially, to arise from
viral infection, so it would be great to compare the
virome of PBC patients with those without the disease.
Maybe you'd identify a consistent pattern suggesting a
specific viral cause.
"Indeed any other disease of unknown aetiology -
identifying specific virome reactivity could give a major
clue as to a causative agent."
And the technique might also shed light onto why new
treatments - immunotherapies - that are being deployed
in the fight against cancers work in some individuals and
not in others.
Prof Elledge commented: "It's possible that the people
that respond [to therapy] are responding because they
are taking advantage of existing immune responses to
viruses, so we are looking at correlation in these patients
to previous viral exposures to see if exposure to a
particular virus makes it more likely to respond."

http://www.bbc.com/news/science-environment-33008590