Genetic fingerprints from viruses

The infections we succumb to, caused by agents like viruses leave genetic fingerprints in their victims. And even though the virus itself may be dead, the sequences of its genetic material can still be obtained from various tissues and specimens and can reveal crucial insights into where those infections came from, and how they evolved. This, in turn, tells us how infections we might encounter in the future may behave. Andrea McCollum works with the US CDC - the Centres for Disease Control, and Izzie Clarke spoke to him about his work...

Andrea - We have a couple of interests: one would be for the smallpox virus itself and how that evolved over time. Then we are also really interested in viruses that were used to vaccinate people against smallpox.

If we can begin to take these old specimens and then fill in gaps in our knowledge, we might better understand what was used, for example, in the United States during the 1800s. And then also for modern-day, it would be very nice if we could determine how these viruses have changed. Have they changed in a way that have affected their ability to infect human cells and to cause disease in humans? Have their infectious properties actually changed to be less infectious over time?

So there’s a lot of really interesting questions that we have that these types of specimens help us begin to fill in those holes and answer the questions.

Izzie - Smallpox has been eradicated, so how exactly can you investigate this?

Andrea - We’re very dependent on looking at older specimens. Some of these older specimens allow us to look at poxviruses, including smallpox, that were present in the 19th century, in the 18th century, and perhaps even further back in time from then. For example, I was initially involved in 2011, we received a call from someone who had visited a museum and had seen what was labelled as a smallpox scab. This actually was a scab that was sent in an envelope with a letter, and it was sent from father to son across the state in Virginia, and it was just after the civil war, so it was around the 1870s. It became clear from reading the letter this was a vaccination scab. The idea is that this scab containing live virus that had been used for vaccination was collected from somebody was being sent to this family member to then be able to vaccinate others.

Izzie - You’re looking at the genetic information of these viruses, does the virus have to be live to take that genetic information and have a look at it?

Andrea - No, it does not. The nice thing about these viruses, they are DNA viruses. Even if the virus itself is dead in the sense that it cannot cause an infection in humans or in other animals, you may still be able to pull out some of that genetic material and then look at it in the laboratory, obtain the DNA sequence and then find out what virus it was. That is one thing we’ve been able to do with the variety of these specimens like the scab that I mentioned in Virginia. Or there have been specimens recently obtained from corpses that have come out of permafrost in Siberia. You can learn a lot about that virus that you’ve uncovered without the virus being alive.

Izzie - What can this genetic information tell us about a virus?

Andrea - One thing that we would immediately be interested in if we found any of these poxviruses is 1) what is the species?  Or is it a combination of species of viruses? Then we want to look gene by gene to see are the genes the same as what we know exist in the viruses that exist today. Then within the genes, you can look at the specific sequence information that’s there to determine has there been a lot of evolution over time? What specific sequences have changed? And maybe come up with hypotheses for why those changes occurred.

Izzie - Can this help us in our understanding of modern-day viruses - we’ve seen a lot with Zika or Ebola?

Andrea - Definitely. You definitely need to do that and so I think it can help us in a variety of ways. It can, again, help us understand how viruses have changed over time which may have implications with the pathology or the ability for these viruses to infect human cells, or not. And I think what’s really nice about some of these older relics is that if you can combine it with documented information. For example, in Virginia with the scab, it was found in a letter, so we had documented information about how it was obtained and then it was used for vaccination. If the specimen came from an actual patient and you have some information about the clinical presentation of that patient, and what the patient experienced as a result of that infection, I think it can help us understand a lot about the ability for these viruses to cause disease. How these viruses are interacting with humans today. And, of course, there’s a lot of really interesting historical information as well.

Izzie - Should we be concerned about these live viruses and their genetic information entering modern society?

Andrea - I think first we definitely need to determine when we find one of these relics is there live virus or not? To date, we have not been able to find live virus. But certainly, that is a concern and that’s something I think we want to determine very quickly and very efficiently. One, for the safety again of the individuals who find these specimens and work with them. And then also we want to make sure that this is not spread further.