Francesca Tomasi received her B.A. from the University of Chicago and is now a microbiologist.
In 430 BC, the Greek historian Thucydides wrote on a bout of plague that tore through his hometown. He made a keen observation: people who had gotten ill and survived a similar bout years ago were able to nurse the sick during this outbreak without becoming sick again. This is the earliest known reference to immunity, our bodies' ability to fight diseases. Even though the exact physiological functions of different immune cells were not discovered and probed until much more recently, humans have been aware of our internal ability to fight diseases for over 2000 years.
Fast forward 2,435 years from Thucydides’ Greece to Francisco Mojica’s lab in Alicante, Spain. In 2005, Mojica and collaborators published a paper that changed our understanding of bacteria and genetic engineering forever. Mojica previously found that bacteria contain short DNA repeats that are regularly interspaced between recurring units. These structures were appropriately named CRISPR, for Clustered Regularly Interspaced Short Palindromic Repeats. In 2005, he discovered that these CRISPR spacers come from somewhere: DNA sequences from bacteriophages, the viruses that prey on bacteria. Furthermore, Mojica found a relationship between CRISPR and bacterial immunity against phages containing this DNA. So in 2005, we discovered that bacteria have immune systems too.
Now fast forward 11 years from 2005. Alternatively, rewind a couple of days from today to February 29, 2016. Scientists at Aix-Marseille University in France discovered yet another immune system in organisms previously never thought to contain one: viruses.
Before getting to the study, we first need some background information on viruses. Viruses are small infectious agents that can only replicate in living cells. They infect all life forms – animals, plants, bacteria, and archaea – and when they are outside of their target cells, viruses exist as virions, or independent particles. These particles contain the virus’s genetic material (DNA or RNA) and a capsid, which surrounds and protects this genetic material. In some cases, an additional envelope encases the virion. Because they carry genetic material, reproduce, and evolve, viruses can be considered life forms. However, because they lack cell structures and the ability to reproduce on their own (viruses hijack our cells to replicate themselves, which is why we get sick), viruses are also not considered exactly to be “alive.” As a compromise, viruses are more like organisms on the brink of life.
Viruses can be tiny, encoding as little as 4 genes, or huge, with hundreds to thousands of genes. The latter type of virus was only recently discovered and is known as a giant virus. There are over 150 different kinds of giant viruses in all pockets of Earth. But if a tiny virus is just as capable of successfully infecting a cell as a giant one, what’s the point of a giant virus? After all, the more genetic material something carries, the costlier it is to maintain.
Remember the bacteriophages mentioned above, viruses that infect bacteria? Well, it turns out that viruses have phages too. These so-called “virophages” were first discovered in 2008. They infect giant viruses just as bacteriophages infect bacteria, in that virophages infiltrate the biochemistry of giant viruses in order to replicate.
So when Didier Raoult and his colleagues in France one day observed that a virophage known as Zamilon was no longer able to successfully infect the giant virus it was previously known to attack (a “mimivirus”), they wondered if a CRISPR-like immune system was to blame. Sure enough, they found that Zamilon-resistant giant viruses contained snippets of the virophage’s DNA in their own genomes. Furthermore, when they studied the sequence of the DNA surrounding the Zamilon snippets in the mimivirus, they found that this DNA encoded a gene product that unwinds DNA, and another one that cleaves it. To test whether these two genes were responsible for the giant virus’s ability to ward off Zamilon infection, the researchers silenced each flanking gene. The result? The mimiviruses were suddenly vulnerable to Zamilon. Raoult and his colleagues named the newly-identified immunity segment of viral DNA MIMIVIRE, which stands for “mimivirus virophage-resistance element.” They suggest MIMIVIRE acts as a viral immune system, though it is still unclear how the giant virus is able to recognize a virophage prior to directing the DNA-snipping enzymes against it.
Our immune systems recognize germs as foreign material and create antibodies against them in order to neutralize their pathogenic activity. Bacteria also recognize viruses by keeping a snippet of their genetic information “on file” so that they can destroy recurring viruses before they can attack them. And now, we know that some forms of viruses – namely, giant ones – contain a third type of immune system. Such a discovery has potential implications in the longstanding debate on the evolutionary history of giant viruses. While some scientists propose that giant viruses recently evolved from cellular life into simplified forms, the discovery of MIMIVIRE might instead imply that giant viruses are actually a lot more ancient. In fact, mimiviruses may have branched off the tree of life before modern cellular life even evolved. For the subsequent billions of years, giant viruses then could have developed features characteristic of viruses as we know them, and cellular life as we know it.