1. Biotechnology Unit: Viruses

2. What do you see here?
Have the students answer the question and use them to facilitate a discussion involving:
the size of the viruses (bacteriophages or phages) that are “attacking” this bacterium.
Since the virus particles are “attacking” the bacterium, ask the students if they think the virus particles are “feeding.”
Ask them if they think the virus particles are alive. As you progress through the lesson, keep asking the students if they have “changed their minds” on this topic.
Continue the discussion by telling the students that viruses are obligate internal parasites, which means that they are incapable of reproducing outside of the host cell.

3. What is the cause: bacteria or virus?
In the late 1800’s Martinus Beijerinck performed this experiment and saw that something “smaller” than bacteria was causing tobacco mosaic disease.
Discuss the experiment that Martinus Beijerinck performed in the late 1800’s to determine the cause of tobacco mosaic disease. The results of the experiment were that the filtered sap could infect healthy plants. He continued to replicate this experiment on the previously healthy plants which had become infected due to sap and was able to show that the infection rate did not decrease. In 1935, Wendell Stanley was able to crystallize the infectious particle for tobacco mosaic disease, a virus, and has since been known as the tobacco mosaic virus.

4. Types of Viruses
Discuss some of the different types of viruses with the students. Have them discuss with a neighbor the similarities and differences between them. For instance:
They all have:
Some type of capsid – even though the “capsid” on the bacteriophage is much more complex than the others
Genetic material (either DNA or RNA)
They differ in that:
Some have a membranous envelope protecting the capsid.
Some have glycoproteins. Ask the students what they think the glycoproteins are used for.
They all have different shapes. Ask the students why different shapes would matter. You can now tie in the overarching theme of structure = function.

5. What are the components of viruses?
A virus typically consists of two main types of biological molecules:
Protein
Nucleic Acids
Basically, there is a protein capsid encasing the genetic material. The capsid is made up of capsomeres. Many viruses have other accessory parts made up of protein.
However, some are encased in membranes (phospholipids), some consisting of glycoproteins.
Which biological molecules make up these two structures?
This should be review but impress on the students how all four major biological molecules can be found in a virus.
There is always genetic material involved (DNA or RNA), which is a nucleic acid. The DNA can be single- or double-stranded. The RNA could either be single- or double-stranded. This might be a great time to introduce them to the fact the DNA isn’t ALWAYS double-stranded and RNA isn’t ALWAYS single-stranded.
The genetic material is encased in a protein coat (capsid) with other protein accessory structures.
If the capsid(s) are surrounded by a membranous envelope, then remind the students what membranes are made out of (membrane proteins, phospholipid made out of phosphate heads and fatty acid tails, cholesterol, etc.). The membranous envelope is derived from the host cell’s membrane.
The membrane itself contains carbohydrates, lipids, and proteins. Sometimes you might find structures called glycoproteins (carbohydrates and proteins).

6. Basic Reproduction of a Virus
This is a basic overview of the the reproduction of a virus. Go over the following steps with them:
The virus injects itself, or its genetic material into a host cell.
The genetic material then replicates and/or is transcribed into viral mRNA.
This viral mRNA is then translated into protein (parts of the capsid, tail fibers, etc.)
Then viral DNA is encased inside capsid proteins and all the part are assembled together to make multiple virus particles.
The new virus particles then “burst out of the cell” (lyse).
They are then able to go out and infect other healthy cells.
You might have to review transcription and translation with them. Discuss how the cell actually does all the work for the virus (DNA synthesis, RNA synthesis, protein synthesis, etc.) Have the students think of what other structures are involved in this process and explain how they all work together to make new virus particles, i.e. ribosomes, tRNAs, amino acids, ATP, DNA polymerase, RNA polymerase, topoisomerase.

7. A cell full of viruses!!! The lytic cycle destroys the host cell.
It produces many new virus particles (phages).
If a phage is only capable of reproducing via the lytic cycle then we call it a virulent phage.
Restriction enzymes have the ability to cut DNA at certain sequences. Some bacteria use these enzymes as a defense mechanism against viral DNA.
The enzymes referred to in the third bullet are the same restriction enzymes discussed in the genetic engineering unit. Make that connection here…

8. Lytic Cycle
This slide and the three that come after it all show the lytic cycle. A bacteriophage, or phage, is a virus that infects bacteria. We see here that there is a bacterium. Ask the student how they know it is a bacterium (it has a single, circular chromosome). Based on the last slide, have the students predict what is going to happen next. Tell them that the phage is able to attach to receptors on the outside of the bacterium which allows it to “dock” to the cell.

9. Lytic Cycle
The students need to see that not only has the phage injected its genetic material into the bacterium but it has also shut down the host cell’s DNA.

10. Lytic Cycle
With the cell’s DNA shut down, the viral DNA uses the cell’s machinery to undergo transcription (DNA is used to make RNA) and translation (RNA is used to make protein, i.e. more viruses).

11. Lytic Cycle

12. Lytic Cycle
Make sure the students see the connection between the word “lytic” and the word “lyse.” To lyse is to cause destruction to the cell membrane and have the cell open up. This is exactly what happens at the end of the “lytic” cycle.
If a phage is only capable of reproducing via the lytic cycle then we call it a virulent phage.

13. …or, the viral DNA can remain dormant
Phages can also reproduce by making copies of its genetic material without actually making any new viruses…YET!
We call this the lysogenic cycle. The viral genetic material gets incorporated into the host cell’s genome. When this happens we call the viral DNA a prophage.
Every time the host cell undergoes cell division…the prophage is copied!

14. Lytic vs. Lysogenic Cycles

15. What implications will this have?
How could the following aspects of the lytic and lysogenic cycles increase rates of evolution?
Viruses have highly efficient replicative capabilities that allow for rapid evolution and acquisition of new phenotypes.
Virus replication allows for mutations to occur through usual host pathways.
RNA viruses lack replication error-checking mechanisms, and thus have higher rates of evolution.
Related viruses can combine/recombine information if they infect the same cell.
Let the student get into groups and discuss each of the aspects seen on the slide. Lead a discussion of these with the students helping connect evolution to the concept of viral reproduction.
Viruses have highly efficient replicative capabilities that allow for rapid evolution and acquisition of new phenotypes.
(Evolution is the change in gene frequencies in a population over time. Therefore, the faster you can get from one generation to the next, the faster the gene frequencies can change, the faster the evolution of that population.)
Virus replication allows for mutations to occur through usual host pathways.
(Mutations are the vehicle by which natural selection can occur. This coupled with rapid reproductive rates causes increased rates of evolution.)
RNA viruses lack replication error-checking mechanisms, and thus have higher rates of evolution.
(This increases the mutation rate, thus increasing the effects of #’s 1 and 2.)
Related viruses can combine/recombine information if they infect the same cell.
(This increases the diversity of the genetic information of the viruses thus “changing the gene frequencies” in the population…thus increasing evolution.)

16. Lytic vs. Lysogenic Cycles
The student should be given a full page copy of this page for their study material.

18. Viral Reproduction including membranous envelopes
Have the student compare and contrast this slide with the slide 8 (overview of virus reproduction). They should see how the virus uses the cell’s machinery to not only make the proteins needed and the genetic material copied, but the virus also uses the host cell to make glycoproteins and uses the cell’s phospholipid bilayer to make a membranous envelope. Ask the students what good this membrane around the capsid would be? (It allows the virus to go undetected as the host’s immune system recognizes it as one of its own and provides receptors on the outside that it to fit perfectly with other cells!)

19. Viruses that attack animals
Viruses that infect animals have the widest range of RNA genomes.
Some of these, called retroviruses, use an enzyme called reverse transcriptase to copy their RNA genome into DNA.
Yes, this goes opposite of the central dogma of biology:
DNA is used to make RNA which is used to make PROTEIN.
HIV is a well-studied system where the rapid evolution of a virus within the host contributes to the pathogenicity of viral infection.

20. Have the students look at this figure and describe the similarities and differences between a regular virus and a retrovirus undergoing reproduction.
This is a basic overview of the the reproduction of a virus.
The virus injects itself, and/or its genetic material (RNA) into a host cell along with the enzyme reverse transcriptase.
Reverse transcriptase causes the viral RNA to be used to make viral DNA.
A second DNA strand complementary to the first is then produced.
This DNA then incorporates itself into the host DNA as a provirus.
The genetic material then replicates and/or is transcribed into viral mRNA, which can be used for the next viral generation OR it can be used as mRNA to be used in translation (production of the glycoproteins, reverse transcriptase, and the capsid proteins).
Capsids are assembled around the viral genomes and reverse transcriptase molecules.
The new virus particles then “burst out of the cell” (lyse).
They are then able to go out and infect other healthy cells.

21. Plant viruses Most plant viruses have an RNA genome.
They spread disease in two main ways:
Horizontal transmission
Entering through the cell walls
Vertical transmission
Inherited from a parent

22. Viroids
Viroids are small, circular RNA molecules that can replicate within the host cell, but do not encode proteins.
They cause disruptions in the regulatory systems that control plant growth.

23. Prions
Prions are infectious proteins that cause brain diseases in mammals. They “reproduce” by turning healthy proteins into infectious proteins (prions). Some diseases caused by prions are Creutzfeldt- Jakob disease in humans, mad cow disease, and scrapie in sheep.