The Viruses Inside of You: Polintons
A companion piece to ‘The Enemy of my Enemy is my Friend.’
By: Sienna Schaeffer
Edited by: Namrata Damle, Katherine Hill
The human genome is littered with odds and ends: non-functional genes, large regions of unintelligible DNA, and thousands upon thousands of repeats. Many of these oddities are the result of human cells’ own processes and mistakes, compounded after thousands of generations. In addition to these relatively mundane quirks, there are many parts of the human genome with a stranger backstory. A significant portion of human DNA is actually ancient viral DNA that has been inserted into our genomes throughout our evolution as eukaryotes*. The vast majority of this viral DNA cannot do much of anything, although a very small portion of it is capable of making copies of itself (1). However, one family of viral elements called the Polintons** may be capable of doing much more.
The Polinton family is a group of very large, very complex transposons. Transposons are (relatively) small segments of DNA that can move around and replicate within the genome. Some transposons are known to be descended from viruses, while others originate from within the human genome. Transposons are plentiful in eukaryotic genomes: they make up 44% of human DNA and 90% of corn DNA (1). Polintons belong to a specific group of transposons known as retrotransposons. A retrotransposon makes an RNA copy of itself which is turned into DNA and then inserted into the genome elsewhere. Transposons and retrotransposons that are descended from viruses can sometimes retain functioning viral proteins. However these elements could never do anything other than replicate themselves within the host’s genome. They have lost the genes that made them true viruses, and exist only as strands of nucleic acids.
This is where polintons differ starkly from all other known transposons. Upon their discovery in the mid-2000s, it was clear that polintons were capable of encoding several viral proteins that a virus would use to replicate its DNA, package that DNA into new viruses, insert its DNA into a host, and more (2). Initially these characteristics distinguished polintons as highly complex transposons, but not necessarily anything more. However, in 2014 it was discovered that some members of the Polinton family also had the genes required to make capsid proteins (3).
Capsid proteins are the proteins that make the outer shells of all viruses. Without a capsid, a virus is just a collection of genes that do not have a container to assemble themselves into. Without a capsid a virus cannot leave a cell, let alone infect a new one. When researchers realized that some polintons had all of the necessary genes required to act as functioning viruses, they proposed that polintons should be recognized as a family of true viruses instead of transposons. They named this hypothetical family the polintoviruses. This finding had enormous implications, but one question stood about above the others: if polintons are true viruses, is it possible that they could become reactivated and start producing full viral particles?
The plot thickened when researchers realized that the polintons were related to a group of viruses known as virophages. Virophages are viruses that parasitize giant viruses, which are huge DNA viruses that infect protists. Each virophage has a corresponding giant virus that it specifically parasitizes by taking over the giant virus’ machinery and hindering the giant virus’ replication. When the similarity between polintons and virophages was discovered, scientists became interested in whether virophage DNA, integrated into the host cell’s genome (kind of like Polintons are integrated into many eukaryotic genomes), could help protect the host cell from infection by giant viruses.
A paper published in 2016 by Matthias Fischer and Thomas Hackl showed that integrated virophage DNA could help protect populations of host cells during a giant virus infection (4)‡. The virophage DNA was integrated into host cells’ genomes by infecting them with the virophage. After this DNA was integrated, it was passed down to daughter cells as an inducible antiviral defense system. When the giant virus infected the host cell, it actually activated the virophage DNA, leading to the production of mature virophage particles. Although the original host cell always died, the virophage particles produced by the giant virus reactivation then went on to slow the spread of the giant virus infection in the host cell population.
This paper provided evidence for several firsts. This was the first evidence of a viral infection actually benefiting a host cell population in this manner. This study also provided the first evidence that reactivation of an integrated viral element is possible under certain conditions. The next step will be to determine if polintoviruses, with their significant genetic similarity to virophages, can also be activated by another virus. If polintovirus reactivation is possible, it could change much of what we know about eukaryotic evolution and the relationship between viruses and transposons. Polintons are widespread amongst eukaryotes‡‡: if they can act as an inducible antiviral defense system like their virophage cousins it could open up a whole new world of antiviral activity that was previously unknown to us.
This whole new world would most likely not include humans. Although we have polintons, the viruses most likely to be able to reactivate polintoviruses (the giant viruses) are currently only known to infect protists. Still, the fact that true viruses may exist inside all eukaryotes, and that some of them may be able to protect their hosts against other viruses, opens up a much more complex and interwoven evolutionary network between eukaryotes, their viral DNA, and viruses.
Footnotes:
* Eukaryotes are all organisms that have membrane-bound organelles. Eukaryotes include all animals, plants, fungi, and protists (amoebas, ciliates, etc.). Bacteria are archaea are not eukaryotes.
** The Polinton family is also known as the Maverick family.
‡ If you are interested in the details of this paper, see the companion piece ‘The Enemy of my enemy is my friend.’
‡‡ Fun fact, polintons make up ~30% of the genome of Trichomonas vaginalis, the protozoa that causes the STD trichomoniasis (5).
References
1. Mills, R. E., Bennett, E. A., Iskow, R. C., & Devine, S. E. Which transposable elements are active in the human genome? Trends in Genetics,23(4), 183–191. doi:10.1016/j.tig.2007.02.006 (2007)
2. Kapitonov, V. V., & Jurka, J. Self-synthesizing DNA transposons in eukaryotes. Proceedings of the National Academy of Sciences, 103(12), 4540–4545. doi:10.1073/pnas.0600833103 (2006)
3. Krupovic, M., Bamford, D. H., & Koonin, E. V. (2014). Conservation of major and minor jelly-roll capsid proteins in Polinton (Maverick) transposons suggests that they are bona fide viruses. Biology Direct,9(1), 6. doi:10.1186/1745–6150–9–6
4. Fischer, M. G., & Hackl, T. (2016). Host genome integration and giant virus-induced reactivation of the virophage mavirus. Nature,540, 288–291. doi:10.1101/068312
5. Pritham, E. J., Putliwala, T., & Feschotte, C. Mavericks, a novel class of giant transposable elements widespread in eukaryotes and related to DNA viruses. Gene, 390(1–2), 3–17. doi:10.1016/j.gene.2006.08.008 (2007)
