Dormant viruses can hide in our DNA and be passed from parent to child

By Ed Yong | March 27, 2010 12:00 pm

HHV6During our early childhoods, the vast majority of us are boarded by a stowaway that can stay with us for the rest of our lives. It can rear its head when we are at our weakest and it can wriggle its way down our family tree into our children and grandchildren. It’s a virus called human herpesvirus-6, or HHV-6 for short. It’s probably in your genome right now.

As its name suggests, HHV-6 is one of the herpesviruses. Unlike other members, it doesn’t actually cause herpes, but it is one of the most common infections in the Western world. It infiltrates the bodies of over 90% of children and it causes a near-universal disease called ‘exanthema subitum’, also known as roseola or three-day fever. The signs of infection soon clear out, but the virus stays put.

Like all herpesviruses, HHV-6 can enter a dormant phase called “latency”, where it stays in our cells after the initial infection has cleared. These stowaways can stay with us for our entire lives but they can sometimes be roused from their slumber to infect again, especially if their host’s immune system becomes compromised. HIV patients, for example, often experience recurring infections. After decades of symptomless dormancy, HHV-6’s reawakening can be severe and debilitating.

Now, Jesse Arbuckle from the University of South Florida College of Medicine has uncovered the virus’s hiding place. Most herpesviruses just leave their genome as a ring of DNA floating about in infected cells. But HHV-6 is a far sneaker infiltrator. It actually shoves its genes into the genome of its host and it targets special structures call telomeres, which sit at the ends of our chromosomes. Telomeres are like the plastic tags at the ends of your shoelaces – they stop long strands of DNA from fraying at the ends, losing valuable information and becoming incorrectly entangled.

Arbuckle worked with four families in which at least two generations had unusually high levels of HHV-6 in their blood. Some had no symptoms whatsoever, others had neurological problems. Arbuckle sampled their white blood cells and went fishing for HHV-6, using glow-in-the-dark molecules designed to recognise the virus’s DNA. When he looked for the telltale glowing dots under a microscope, he saw that every one sat at the tips of the patients’ chromosomes, and nowhere else (see below). This virus clearly specialises in breaking into telomeres.

HHV6 DNA shows up as red dots at the tips of the blue chromosomes - that's where the telomeres are

It does it using a spot of genetic mimicry. Telomeres are incredibly monotonous and ours consist of the sequence TTAGGG repeated again and again. As it happens, HHV-6 has exactly the same sequences in its own genome, making it easy for it to sneak its sequences into ours.

In its latent state, HHV-6 can bide its time until conditions are right for its comeback debut. Arbuckle managed to trigger its re-emergence using a chemical called trichostatin A (TSA) that also reactivates other dormant herpesviruses. When he cultured cells from his infected family, he found that a dose of TSA led to rising levels of viral DNA. The latent HHV-6 genes could produce new viruses, capable of starting fresh infections.

Finding HHV-6’s hiding place is an important discovery, but there are still a lot of questions left to answer. When the virus first infects a host, what makes it smuggle its genes into telomeres, as opposed to continuing its normal infectious life cycle? Once inside, what’s the natural trigger that reactivates it? And does the presence of these viral stowaways disrupt the telomeres? The last question is particularly important – telomeres are incredibly important for protecting our DNA from harm and if problems with telomeres have been linked to both cancer and mental retardation.

The implications of HHV-6 infections become even bigger when you consider that the virus can pass down from parent to child. Arbuckle showed that family members with latent HHV-6 infections carried the same viral sequences in their telomeres. This means that once the virus finds its way into someone’s genome, it can become a genetic heirloom, unwittingly inherited from parent to child. Does the child also inherit a risk of disease, given that the virus could pop out at any time? Or do their immune systems get a benefit against other herpesviruses, given that they’ve had experience with viral sequences right from birth? Only time, and more research, will tell.

Reference: Arbuckle, J., Medveczky, M., Luka, J., Hadley, S., Luegmayr, A., Ablashi, D., Lund, T., Tolar, J., De Meirleir, K., Montoya, J., Komaroff, A., Ambros, P., & Medveczky, P. (2010). The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro Proceedings of the National Academy of Sciences, 107 (12), 5563-5568 DOI: 10.1073/pnas.0913586107

More on genome-infiltrators:

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Comments (8)

  1. Ed, you have a gift with words. Especially love the shoelace cap/telomere analogy — and I’m probably going to steal that from you at some point in time (hey, imitation is the greatest form of flattery!)

    One thing that struck me after reading this PNAS paper is what other viruses may do this (i.e. ones we may not know about yet). Also: although the body’s genetic machinery could be “blind” the HHV-6 hiding out in telomeres, could the virus’ presence actually help maintain telomeres — and therefore serve as a sort of symbiotic relationship?

  2. Thanks Dave! Although it’s definitely not mine. I’ve heard it a few times before and I think it’s even on Wikipedia. Amusingly, the term for those things at the end of shoelaces is “aglet” but I figured that too few people would know the term that I’d be explaining a technical term with another technical term. ;-)

  3. Congrats on the new host, Ed! Looks good. and btw I didn’t even need to change my google reader feed, it updated itself automatically.

    Good luck!

  4. katesisco

    yes, we puzzlers know it is an aglet and more amazing is this virus’ ability to pass on. Just imagining how many other do the same. And Yes, everything is connected. I am so astounded when I read time after time how poisoning this has a repercussion that affects something else.

    As we older folk know, our economic cycles endlessly repeat; we are now doing the OK thing with tobacco, alcohol, gambling, drugs, and when this wears thin, we will swing the pendulum the other way, etc. So, the campaigns we signed onto like keeping cigarette smoking and alcohol advertising off tv are now in antecedence; so these finding about science are wonderful even if they indicate that when we open a door, all we will find is another dozen doors.

  5. Daniel J. Andrews

    so these finding about science are wonderful even if they indicate that when we open a door, all we will find is another dozen doors.

    Emphasis added.

    I’d say these findings about science are wonderful because when we open a door we will find another dozen doors.

  6. @Ed Yong
    Rare words are like fine wines for me. They are to be savored and enjoyed when you gat them. I am one of the few English speakers in this world who actually knows what an aglet is. I was looking for it in your post. While I was mildly disappointed to not find it in the main post, I was heartened to see you bring it up in the comments. :-)

  7. Nathan Myers

    The fun thing about that word “aglet” is that you don’t need to explain it. Say telomeres are like thost aglet things at the ends of readers’ shoelaces, and the word finds its own way into readers’ brains, just as the virus finds own its way, albeit less helpfully, into their nuclei.

    We need another retrovirus that expresses the antisense to some essential part of HHV, that is triggered to be expressed whenever HHV is. But when is that?

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