Background
There is a vast amount of microbes that exist in our world and yet, most of them seem to lack the level of disdain that surrounds the reputation of viruses. While various protozoa, bacteria, and fungi share many of the same qualities as viruses, they don't quite seem to strike the same type of fears in us as viruses do. This is probably due to the fact that many viruses cause serious illness in humans and domesticated animals, as well as inflict damage on crop plants. The shared relationship that microbes and humans possess has long been known. However not until relatively recently, have we discovered just how close our relationship has been. There is a large amount of research that suggests the evolution of our species is directly connected to the evolution of viruses.
With this in mind, I believe it is critical for my students to understand the significance of viruses in our world. By my students achieving this level of understanding, they will reinforce many of the major themes learned throughout the year in Biology. This includes, most importantly, being able to identify viruses' role in this constantly changing world and how science can be used to validate viruses' significance in our civilization.
Furthermore, it will help my students to see that while viruses do cause disease, they can also be useful as tools for our survival. This should prepare them for any encounters they may have in their lives with viruses, which is important since the war between humans and viruses seems to have no end in sight.
Virology History
Before any progress is made in the unit, my students must explore some of the fundamentals of Virology. They must then apply what they learn to the impact viruses have had on human civilization. It was only 100 years ago that viruses were shown to be filterable and therefore distinct from bacteria as possible agents of infectious disease. Before this point we were not exactly sure what caused our diseases and infections. There were many hypotheses and beliefs about what could explain the various maladies we experienced, some very close to what we understand today about viruses, and others that were completely off base. It wasn't until 60 years ago that the composition of viruses was described, furthering our understanding of what a virus is and what a virus does. Within the last 20 years, however, the revolution of modern biotechnology has led to an explosive increase in our knowledge of viruses and their interactions with their hosts. Over this time, our perception of viruses has changed so much that now there is an increasing movement towards viewing Viruses as tools of study that can increase our chances of survival. Viruses have also provided a great service by allowing us a deeper understanding in the fields of gene cloning, and interactions of viruses with the immune system; in a sense, these studies tell us as much about human biology as the work has told us about the viruses themselves (James H. Strauss 2002).
Virus Life Cycle
In order for viruses to survive they need a host. This by nature makes a virus a parasite. Their entire existence is directly connected to their ability to find a host that will allow them to proliferate. For this to happen, a virus must infect a host and take over the cell or cells to produce more virus copies (James H. Strauss 2002). When a host cell is infected, all of its metabolic functions are then taken over for the purpose making virus copies. Once the cell is high jacked to begin the process of replicating more copies of the virus' genes, it is also instructed by the virus to create additional viruses that will exit the cell and infect other nearby cells. This is accomplished by releasing the virus genome into the cytoplasm of the cell, instructing the cell to replicate the virus genome to make more viruses. The point of a virus, like all organisms, is to survive and reproduce; thus, viruses have evolved ingenious methods to accomplish these tasks.
The first characteristic of a virus that makes this possible, is that most viruses encode enzymes required for replication of the genome and the production of mRNA. The next thing that must occur is the production of proteins. But not just any proteins, these are specific proteins that are made within the cell and used to assemble progeny viruses. These specific proteins may be coded in the virus genome, or coded by genes that already exist in our own genome (originating from genes that entered our genomes long ago in human evolution) or they target more complicated proteins that are required for virus assembly but do not exist in the virus' genome. Thirdly, many large viruses can code for proteins that block defense mechanisms of the host, making it easier for the virus to integrate into the host cell. This strategy prevents our highly evolved immune defense mechanisms from eliminating the virus infection, and prevents the host cell from recognizing the intrusion of foreign DNA(James H. Strauss 2002).
Classification of Viruses
The classification of viruses largely depends on the genome of the virus and how it replicates, in addition to the virus' morphology (what the virus look like). To avoid spending too much time discussing the various ways in which viruses can differ, I will focus on highlighting the most crucial differences. More information on the classification of viruses can easily be found online or in books that specialize on the topic. Viruses can essentially be broken down into 3 broad classes, with each of them possibly having independent origins of evolution. One class, which includes the poxviruses and herpesviruses among many others, contains DNA as the genome, whether single stranded or double stranded, and the DNA genome is replicated by direct DNA —> DNA copying(James H. Strauss 2002). The herpesviruses have benefited greatly from this characteristic giving them the ability to remain in the human body undetected by our immune systems for an entire human lifetime. More details on the herpesviruses will be discussed later in the section.
In contrast, the second class of virus contains RNA as the genome and the RNA is replicated by direct RNA —> RNA copying. Viruses of this sort tend to have a more difficult time infecting a host, since virus-encoded proteins are required to form a replicase (enzyme for replication) to replicate the Viral RNA, since cells do not possess (efficient) RNA —> RNA copying enzymes(James H. Strauss 2002). Because this class of virus has extra obstacles to overcome, it would seem as though these particular viruses would not be as virulent, or deadly, as others. However, because this class of virus has an RNA genome, it also experiences a much higher rate of mutation than would a DNA virus. Accordingly, the high mutation rate of RNA gives it a better chance to make genetic variants that can be naturally selected to survive, sometimes producing strains of virus that our bodies are completely unprepared to fight off. This was the case for the yellow fever epidemic that has been plaguing our society for centuries, if not longer, costing hundreds of thousands of lives throughout our history.
The third class of viruses encode the enzyme reverse transcriptase (RT), and these viruses have an RNA —> DNA step in their life cycle. The genetic information encoded by these viruses thus alternates between being present in RNA and being present in DNA. This class of viruses is of particular importance to this unit because of its versatility and virulence in our world. You will find that, this class of virus is often referred to as a Retrovirus, named so because of the way it replicates in its host. More specifically, it replicates through the process of reverse transcription, using the reverse transcriptase enzyme to produce DNA from an RNA genome. This is opposite to the outdated 'central dogma' (assertion that RNA can only come from DNA), hence the origination of 'retro' (backwards) in the name retroviruses. These types of viruses are unique to all other viruses and can be very hard to eliminate because of their high mutation rates and the fact that they possess the ability to integrate into human cells and avoid detection by our immune system(James H. Strauss 2002).
Replication Cycles
The replication cycles of viruses also help to distinguish them from each other. The first task a virus has to accomplish, before replication can begin, is entry into the cell. During this stage viruses will bind to receptor sites on the cell if the correct protein interaction is or is not available to initiate the binding and infection process. Binding usually occurs in several steps. Some receptors on cells exist in high concentrations, and others do not. Thus, it behooves a virus to evolve a structure that matches with receptors that are most abundant. With this in mind, it shouldn't be surprising that viruses have evolved, through natural selection, to use receptors that are the most abundant on cells(James H. Strauss 2002).
Penetration
Once the virus has completed the necessary stages for binding to a receptor on a cell, the next stage required for successful infection is the introduction of the viral genome into the cytoplasm of the cell(James H. Strauss 2002). This can occur in various ways, all of which have to integrate into the basic functioning of the cell. Some cases involve a subviral particle containing the viral nucleic acid (DNA or RNA) being introduced into the cell. Other cases involve only the nucleic acid being introduced.
For enveloped viruses, penetration into the cell involves fusion of the envelope of the virus with a cellular membrane. When this occurs, a dramatic rearrangement of proteins allows for receptors to fuse with the virus envelope and permit entry into the cell. This method has proven to be very efficient, demonstrating in some well-studied cases almost all particles succeeding in initiating infection(James H. Strauss 2002). For viruses that lack an envelope the process seems to be a bit unclear. However, the general belief is that a rearrangement of structure is initiated by the binding of the virus to the receptors.
Replication and Expression of Virus Genome
There are many more detailed steps that take place during the replication cycle of viruses that I will not describe in this unit. However, before I move on from replication, I will briefly explain what happens after a DNA virus enters into the cell for replication, since much of the unit focuses on DNA viruses.
The first thing that should be noted is that after entry into the cell the virus DNA will be transported to the nucleus, or control center of the cell. There it is transcribed into mRNA by host RNA polymerase. Viral mRNAs are then translated by host ribosomes in the cytoplasm, and newly synthesized viral proteins are transported back to the nucleus. After the DNA genome is replicated in the nucleus, either by host DNA polymerase or by a new viral-encoded polymerase, progeny virus particles are assembled and ultimately released from the cell(James H. Strauss 2002).
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