Test unravels history of infection

Herpes simplex virus

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 80, 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.”

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