As a little kid, I scared pretty easily. Thunderstorms were rough, and if the tornado sirens went off then I panicked really quickly. Movies and TV shows were an issue too. The monsters from Scooby-Doo gave me nightmares sometimes, especially the Zombie Island movie. My mother could tell you a funny story about me hiding behind the couch. Snow White was a no-go, the Wicked Witch terrified me, as did that seen where Snow White is running through the forest and all the trees come alive. I didn’t like Alice in Wonderland, either. I can’t really remember why, I think it was a combination of the Cheshire Cat, the Red Queen’s beheadings, and the generally trippy-ness of that whole world. Nonetheless, I grew up and became a (sort of) normal kid. I hadn’t thought of the Red Queen in years, until a lecture I had this spring in one of my classes. The professor who was teaching this section was talking to us about Viral Evolution. To open the class, he introduced a topic known as the Red Queen Hypothesis. This hypothesis is based on a line by the Red Queen said to Alice in a dream from Through the Looking Glass.
“Now, here, you see, it takes all the running you can do to keep in the same place.”
In high school and/or in college, you probably learned about Evolution. Charles Darwin hopped on a boat, sailed all over the place, and took a ton of notes. His written work that he eventually published, On The Origin of Species, became the foundation for the evolutionary biology concepts we have established today. Organisms must adapt to their environments in order to survive, those who possess the best traits are the most fit to produce capable offspring, etc., etc. A topic that you might not have heard as much about is co-evolution. When it comes to humans and viruses, this topic contributes to understanding the relationship we have with them. The Red Queen, of all people, can give us some help.
As you might already know viruses are not considered “living” organisms, due to their inability to replicate successful in the absence of a host. Essentially, they must hijack cellular machinery of a host in order to fulfill their metabolic and replicative requirements. Different viruses are capable of infecting all sorts of hosts, from bacteria to plants to insects to humans.
Relative to humans and other multicellular organisms, viruses are incredibly simple. Many of them have only a small strand of genetic material (DNA or RNA) surrounded by a protein structure called a capsid. An assembled and potentially infectious single virus unit is referred to as a virion. Virions are capable of entering a host through a massive variety of methods, and once inside they have one most important goal- make more of themselves. This is an important concept to note. The goal of a virus is really not to kill the host it enters. In that case, the host is a dead end. If a host dies, the virus has nothing to pilfer from. Ideally, virions would like to hide out undisturbed and make as many copies of themselves as possible. Here’s where our immune system comes in. Our bodies are constantly patrolled by certain subtypes of white blood cells that make up our innate immunity, protecting us from invaders we have never seen before. Some of these cells are macrophages, neutrophils, dendritic cells, and natural killer cells. When they recognize foreign material, they possess signaling mechanisms that trigger a heightened immune response and eventually give our body a memory against that specific version of the pathogen.
It’s at this junction that the Red Queen Hypothesis begins to help our understanding. In order for viruses to persist, they must new, clever find ways to evade our immune system, which is designed to rid the virions from our body. Initiate the running in place, a constant arms race between host and pathogen. So why do some viruses cause so much more damage than others?
One answer to this question can be found in extremely simple design of the virus itself. When human cells divide there are proofreading mechanisms that attempt to ensure all of the copied genetic material has been correctly duplicated. Overall, our cells are pretty good at this with an error rate of roughly 1 in 100,000,000 base pairs. On the other hand, many viruses have RNA genomes that are absent of proofreading mechanisms. This causes them to mutate at rates drastically quicker than humans. Although this would be undesirable for us, viruses can use this high error rate to their advantage. While rapidly mutating they become more difficult for our immune system to detect, or perhaps find new ways to enter host cells. HIV, for example, can mutate so rapidly that a single infected individual can house quasispecies, a phenomenon that has contributed to the challenge of vaccine design. As viruses like HIV and others continuously mutate, our immune system must find different methods to recognize them and stymie their efforts at replication and dissemination.
The dance proceeds with the element of co-evolution. Many of the viruses that are most problematic to us have very recently jumped to humans. Viruses like HIV, Zika, Ebola, and Dengue, have become exposed to much of the world population in recent time. Others we have been exposed to for so long that they are actually apart of who we are today. Ultimately, this makes some sense. As the length of exposure increases, our immune system learns the ins and outs of defending against a newly pathogenic virus. At first though, we must survive long enough to combat them. In this sense we evolve together, with viruses consistently finding new ways to infect and persist inside us and humans trying to develop equally novel methods to rid them from our body as we become more familiar with their avenues of pathogenicity.
Our immune efforts are of course aided by modern medicine, as many historically pathogenic viruses have been largely eradicated from the human population. Inflictions like smallpox, measles, mumps, and polio are scare in the developed world. However, there are still many viral riddles to solve. And the next time you wonder why you are sick for the 10th straight year with the common cold or influenza, just maybe a silly line from a children’s story will help explain. Chances are high that you’ll be healthy again in about a week. As humans change, so do the tiny things that try to live inside us. The race goes on.
The 520 Wire 