The viruses inside us

Dendogram of endogenous retroviruses. Source: Wikipedia.

Last month I posted a discussion on a PNAS paper that reported the discovery of a new class of viruses, called pithoviruses, found in a layer of Siberian permafrost. In their paper [1], the researchers conclude:

“Our results further substantiate the possibility that infectious viral pathogens might be released from ancient permafrost layers exposed by thawing, mining, or drilling.”

I found this possibility intriguing both from a scientific point of view as well as a sci-fi point of view: there are plenty of books out there on zombies and aliens, but what about ancient viruses that thawed from the ice thanks to global warming?

An attentive reader, though, didn’t buy the sci-fi “threat” and asked in the comments whether viruses are necessarily bad. Normally we think of viruses as pesky little things. And while most will make us sick for a short time only, some can indeed be deadly, and others can inflict long-term complications.

The reader who asked that question, however, is absolutely right: over the course of evolution, viruses have been beneficial to us. Viruses have driven genetic diversity by transferring genes across species, and in fact, we still carry remnants of viral genes in our DNA, comprising roughly 8-10% of our genome. They are called “endogenous retroviruses”, or ERV.

In the rest of this post I will address two questions:

  • What are those viral genes doing in our genome?
  • How did they get there?

What are viral genes doing in our genome?

Most of them are doing nothing. They are “deactivated”, meaning they do not code for proteins. Our genome is made of many redundant elements that over the course of evolution were silenced because no longer useful, only to be turned on again later on when a new adaptation happened.

One such example is the placenta, where endogenous retroviruses have been found to be expressed [2-4] and play a role in the growth and implantation of the tissue. We can only speculate on why retroviral genes are expressed in the placenta, but the hypothesis is indeed quite interesting: in order to survive, retroviruses debilitate the immune system. In general, this is not a good thing for the body, except in one very special instance: an embryo is literally a parasite growing inside the mother’s body. It carries extraneous DNA and, under normal circumstances, something carrying extraneous DNA would be considered an antigen and attacked by the immune system. Therefore, the expressed viral proteins found in the trophoblasts, the outer layer of the placenta, would have the role of suppressing a possible immune reaction against fetal blood.

Another property viruses have is that of cell fusion: they literally “merge” cells together into one membrane. A second hypothesis is that this property is used during the development of the placenta to build a barrier between the maternal circulation and the fetal circulation.

How did viral genes end up in our genome?

A virus enters the body of a host with the sole purpose of replicating. In order to do so, viruses hijack the cell’s own replicating machinery. Retroviruses in particular carry strands of RNA which, once injected inside the cell, are turned into DNA that is then carried inside the cell nucleus and integrated into the cell’s genome. This ensures that once the cell replicates, the bit of viral DNA is replicated too.

There is a special set of cells, however, such that when the virus infects them it literally gets stuck. These cells are the gametocytes, a.k.a. oocytes in women, and spermatocytes in men, which do not duplicate unless they get fertilized. But by then the virus is no longer active. It’s literally stuck, in the sense that the integrated viral DNA now cannot replicate and cannot escape the host’s DNA. It’s just a bit of non-functional DNA that gets duplicated along as the embryo grows. The new individual now carries the viral genes in every cell of his/her body, even in the gametocytes, and hence the viral genes will be inherited by future generations as well.

And that’s how viruses ended up in our genome a long, long time ago and have literally become “evolutionary fossils.” In fact, by looking at these endogenous retroviral sequences, scientists are able to reconstruct the evolution of ancient viruses.

References

[1] Legendre, M., Bartoli, J., Shmakova, L., Jeudy, S., Labadie, K., Adrait, A., Lescot, M., Poirot, O., Bertaux, L., Bruley, C., Coute, Y., Rivkina, E., Abergel, C., & Claverie, J. (2014). Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology Proceedings of the National Academy of Sciences, 111 (11), 4274-4279 DOI: 10.1073/pnas.1320670111

[2] Emerman M, & Malik HS (2010). Paleovirology–modern consequences of ancient viruses. PLoS biology, 8 (2) PMID: 20161719

[3] Dunlap KA, Palmarini M, Varela M, Burghardt RC, Hayashi K, Farmer JL, & Spencer TE (2006). Endogenous retroviruses regulate periimplantation placental growth and differentiation. Proceedings of the National Academy of Sciences of the United States of America, 103 (39), 14390-5 PMID: 16980413

[4] Dupressoir A, & Heidmann T (2011). [Syncytins – retroviral envelope genes captured for the benefit of placental development]. Medecine sciences : M/S, 27 (2), 163-9 PMID: 21382324

 

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